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Training reduces autonomic cardiovascular responses to both exercise-dependent and -independent stimuli in humans
Autonomic Neuroscience: Basic and Clinical 91 Ž2001. 76–84 www.elsevier.comrlocaterautneu
Training reduces autonomic cardiovascular responses to both exercise-dependent and -independent stimuli in humans Saoirse E. O’Sullivan) , Christopher Bell Department of Physiology, Trinity College Dublin, Dublin 2, Ireland Received 5 December 2000; received in revised form 13 February 2001; received in revised form 23 April 2001; accepted 26 April 2001
Abstract Training attenuates the sympathetic pressor response to dynamic exercise. However, it is uncertain how training alters other patterns of cardiovascular autonomic activation. Therefore, we have quantified circulatory responses to a series of standard autonomic tests in highly fit and unfit subjects and examined the effects of a short-term training programme on these responses. Subjects were defined as either unfit Ž n s 8. or fit Ž n s 8. on the basis of training history and a maximal fitness test ŽVO 2peak 54 " 2.3 cf. 68 " 2.8 Žml miny1 . kgy1 , means" S.E.M., P - 0.05.. On a separate day, the blood pressure, heart rate and forearm vascular conductance responses to a sustained handgrip to fatigue, 2 min mental arithmetic and 2 min of cold exposure were measured. All stimuli were associated with elevated blood pressures and heart rates, but these responses were significantly attenuated in the trained group. In the untrained subjects, forearm vascular conductance increased during exercise Žfrom 0.032 " 0.004 to 0.05 " 0.007 Žml miny1 . 100 mly1 mm Hgy1 , P - 0.05. and during mental arithmetic Žfrom 0.028 " 0.003 to 0.04 " 0.006 Žml miny1 . 100 mly1 mm Hgy1 , P - 0.05., but trained subjects showed no rise in conductance during either test. All untrained subjects undertook a moderate intensity 5-week training programme, which significantly increased VO 2peak Ž54 " 2.3 to 57 " 2 Žml miny1 . kgy1, P - 0.05.. Qualitatively similar blunting of pressor, tachycardic and vasodilator responses were seen in this group post-training. These results demonstrate that the blunting of sympathetic vasomotor activation that follows training is not restricted to reflexes associated with exercise, and does not depend on training being prolonged or intense. q 2001 Elsevier Science B.V. All rights reserved. Keywords: Sympathetic activity; Training; Mental stress; Heart rate; Blood pressure; Muscle blood flow
1. Introduction Chronic training is associated with lower exercise heart rates at any given workload ŽScheuer and Tipton, 1977.. This has been attributed in part to a reduced sympathetic pressor response, evident by decreased plasma catecholamines ŽBarnard, 1975; Scheuer and Tipton, 1977; Winder et al., 1978. and decreased muscle sympathetic nerve activity ŽRay and Hume, 1998.. Regular training also leads to resting bradycardia, which is cited as being due to an alteration in autonomic control; increased parasympathetic activity, decreased sympathetic activity or a combination of both ŽScheuer and Tipton, 1977.. Chronic training is also associated with reduced resting blood pressure, which may also involve reduced resting sympathetic nervous activity; however, this issue
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Corresponding author. Tel.: q353-1608-3545; fax: q353-1608-3545. E-mail address: [email protected] ŽS.E. O’Sullivan..
remains equivocal. Evidence which suggests reduced sympathetic output with training includes decreased plasma catecholamines, catecholamine spillover and muscle sympathetic nerve activity ŽScheuer and Tipton, 1977; Barnard, 1975; Grassi et al., 1994; Huonker et al., 1996.. However, several other studies have reported no change in sympathetic nerve activity with training ŽSeals, 1991; Ray and Hume, 1998.. In addition to the possible effects of training on both exercise and resting sympathetic activity, the sympathetic component of baroreflex control may be altered after training. A reduced cardiac sympathetic response to depressor doses of nitroprusside ŽKingwell et al., 1992. and greater reductions in heart rate and muscle sympathetic nerve activity to pressor doses of phenylephrine ŽGrassi et al., 1994. have been observed post-training. Comparable effects have been shown after training in animal studies, wherein the baroreflex response of renal sympathetic nerve activity is decreased ŽDiCarlo and Bishop, 1988; Negrao et al., 1993..
1566-0702r01r$ - see front matter q 2001 Elsevier Science B.V. All rights reserved. PII: S 1 5 6 6 - 0 7 0 2 Ž 0 1 . 0 0 2 8 8 - 0
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We have previously observed that reflex heart rate responses to the Valsalva manoeuvre and to standing are altered in magnitude in athletes ŽO’Sullivan and Bell, 2000.. However, some investigators have not found training to have an effect on the cardiovascular responses to stimuli such as a cold pressor test or isometric exercise ŽSeals, 1991.. Therefore, the aim of this experiment was to revisit the notion that training affects cardiovascular control, with the hypothesis that autonomic control is affected in a non-specific, exercise-independent manner. To test this, we have assessed the effect of different levels of fitness on blood pressure, heart rate and forearm conductance responses to a series of standard autonomic reflex tests. The tests chosen were a sustained handgrip, mental arithmetic and the cold pressor test. While all three of these stimuli evoke sympathetically mediated rises in total peripheral resistance and blood pressure, they exert differential effects on the other parameters measured. Collectively, these tests allow evaluation of a variety of central sympathetic pathways, carrying information both linked to and independent of those conveying the somatic information associated with exercise. In addition to crosssectional data, we have studied the effects of training on autonomic control longitudinally in previously unfit subjects who underwent a moderate intensity, short-term exercise programme.
2. Materials and methods 2.1. Subjects Sixteen healthy male subjects Ž21–30 years. were recruited on the basis of performing Ž n s 8., or not performing Ž n s 8., regular physical training more than three timesrweek. Height and body masses were recorded and subjects underwent a medical examination to ensure that there were no contraindications to maximal exercise. There was one smoker Ž10rday. in each of the groups. The aims and procedures of the study were explained both orally and in a written document. Subjects signed an informed consent form before testing. All procedures were approved in advance by the Federated Dublin Voluntary Hospitals and St. James’ Hospital Research Ethics Committee. 2.2. Experimental protocol Subjects were required initially to attend the laboratory on two occasions. They were instructed to abstain from caffeine, alcohol, nicotine and exercise for 12 h before an experimental session, in an effort to reduce any effect of stimuli on the cardiovascular system. All testing took place between 0900 and 1300 h at an ambient temperature of 208C. Session 1 comprised of a medical examination, followed by a maximal oxygen consumption incremental exercise test to quantify fitness level. Subjects were also
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familiarised with the experimental procedure for the stress tests during this session. They then reported on a second day for testing, wherein the heart rate, blood pressure and forearm blood flow responses to sustained handgrip, mental arousal and cold exposure were measured. 2.3. Maximal fitness testing Each subject performed a standard incremental fitness test on a Monark 824E cycle ergometer to measure peak oxygen consumption ŽVO 2peak .. The test procedure was explained beforehand and subjects were instructed to continue exercising until exhaustion. The test consisted of 3-min increments beginning at 60 W and increasing by 30 W every 3 min. Heart rate ŽPolar Electro, Finland. and blood lactate concentration ŽYellow Springs Instruments, Ohio. were measured during the last minute of each workload. Metabolic parameters were measured continuously using a Metalyser gas analysis system ŽCORTEX Biophysik, Germany., which was calibrated daily. VO 2peak was taken as the peak oxygen consumption value was reached. 2.4. Sympathetic actiÕation testing During the testing session, subjects were seated comfortably in an upright position. A standard frontal plane ECG was recorded continuously via a MacLab data acquisition system and displayed together with beat-to-beat heart rate. Forearm blood flow was measured continuously in the non-dominant limb by venous occlusion plethysmography, using a gallium–indium strain gauge ŽMedaSonics, Newark. and inflation of an occlusion cuff on the upper arm to a pressure of 40 mm Hg for 4 s every 14 s. Arterial pressure was measured by auscultation from the brachial artery, using phase V Korotkoff sounds as diastolic pressure. The investigator measuring blood pressure was blinded to the training status of the subjects. Mean arterial pressure was calculated as one-third systolic pressure plus two-thirds diastolic pressure. Forearm vascular conductance was calculated by dividing forearm blood flow by mean arterial pressure. Subjects rested for 10 min before the onset of the experiment and initial baseline values for all parameters were obtained at the end of this period. The subjects were then required to perform each of the following tests in turn. Care was taken to ensure all parameters had returned to a stable baseline before presentation of the next stimulus. Ža. Sustained handgrip: Using a handgrip dynamometer, sustained isometric contraction of the dominant hand was maintained at 50% of maximum voluntary contractile force until volitional fatigue. A visual display of the force developed was provided to assist the subject to maintain the appropriate contraction. Žb. Mental arithmetic: Subjects were instructed to continuously subtract the number seven from a three-digit number as quickly and accurately as
S.E. O’SulliÕan, C. Bell r Autonomic Neuroscience: Basic and Clinical 91 (2001) 76–84
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Table 1 Physical and resting cardiovascular characteristics of fit and unfit subjects, and before and after training Fit Height Žcm. Body mass Žkg. BMI Žkg my2 . VO 2 peak ŽŽml miny1 . kgy1 . Heart rate Žbeat miny1 . Mean arterial pressure Žmm Hg. Forearm conductance ŽŽml miny1 . 100 mly1 mm Hgy1 .
Unfit
Post-training
183"2.9 80"3 24"1 68"2.8
177"2.2 75"3.4 24"1 54"2.3 )
74"3.3† 23"1 57"2†
57"3.4 88"2.4
70"3.3 95"1.2 )
67"2.9 92"2.7
0.053"0.01
0.032"0.004
0.062"0.02
possible, for a 2-min period. Žc. Cold pressor test: The right foot was immersed up to the ankle in a basin of iced water Ž2–38C. for 2 min. In parallel experiments, we compared the magnitudes of cardiovascular responses to each test when repeated over several weeks in order to ascertain any habitual effect. No indications were seen on the diminution of responses over time Ždata not shown..
2.5. Training programme Following the initial testing sequence, all untrained subjects underwent a 5-week supervised training programme, consisting of three 30-min sessions per week at 60% VO 2peak on a Monark 824E cycle ergometer. Posttraining, subjects performed a second maximal fitness test and a second series of stress tests. 2.6. Statistical analysis Group results were expressed as means" S.E.M. and were analysed with unpaired Žfor trained versus untrained results. and paired Žfor pre- and post-training, and intragroup over time. Student’s two-tailed t-tests. P - 0.05 was considered significant.
3. Results 3.1. Subject characteristics Physical and resting cardiovascular characteristics of fit and unfit subjects and pre- and post-training are presented
Fig. 1. Mean " S.E.M. mean arterial pressure, heart rate and forearm vascular conductance at rest and 100% fatigue during the sustained handgrip test in fit Žopen circle. and unfit Žclosed square. subjects, and post-Žclosed circle. training, showing the blunting effects of training on the exercise pressor reflex. An increase in forearm vascular conductance in the contralateral arm during isometric exercise was seen in the unfit group, but not in the fit group or post-training. ) Denotes a significant difference Ž P - 0.05, ) ) P - 0.01. between groups. §Denotes a significant increase from resting values.
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in Table 1. There were no significant differences in height, body mass or Body Mass Index between the fit and unfit groups. The subjects recruited as potentially fit had higher VO 2peak values than those in the untrained population, who were regarded sedentary on the basis of the fitness level ŽPlowman and Smith, 1997.. Post-training, previously untrained subjects showed a small Ž5%. but significant increase in fitness typical of 5-week training at the training intensity and frequency undertaken ŽPlowman and Smith, 1997. Žsee Table 1.. Both time to fatigue Ž16.5 "1.2 cf. 19.8 " 1.2 min, P 0.05. and the heart rate at lactate threshold Ž131 " 6 cf. 145 " 3 beat miny1 , P - 0.05. during the fitness test were also significantly improved by training. A small decrease in body mass was seen post-training, but there was no significant change in Body Mass Index. Resting heart rates and blood pressure after the initial rest period were lower in the trained than in the untrained population; however, before each stimulus was presented,
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there was no significant difference in the mean arterial pressure between both groups. Forearm vascular conductance was similar in all groups. Short-term training had no significant effect on the magnitude of any cardiovascular parameter. 3.2. Sustained handgrip There was no significant difference in time to fatigue between fit and unfit subjects Ž121 " 12 cf. 111 " 15 s.. Fig. 1A–C shows the cardiovascular responses of trained and untrained populations to the sustained handgrip test. In both groups, there were progressive elevation of heart rate and blood pressure. However, the magnitudes of these responses were significantly higher in the untrained group, with heart rate increasing by 34 beat miny1 compared with 19 beat miny1 in the trained group Ž P - 0.01, Fig. 1A. and mean arterial pressure rising by 45 mm Hg compared with 29 mm Hg Ž P - 0.05, Fig. 1B.. The reduced pressor
Fig. 2. Mean " S.E.M. systolic and diastolic blood pressure responses over time in fit Žopen circle. and unfit Žclosed square. subjects, and post-training Žclosed circle. during the sustained handgrip, mental arithmetic, and cold pressor test. Fit individuals tended to have lower diastolic pressure values during each test. Post-training, both the systolic and diastolic pressure responses to isometric exercise was reduced, but during mental stress, only systolic blood pressure was affected. ) Denotes a significant difference between groups.
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response of trained subjects involved, decreases in both diastolic and systolic limits ŽFig. 2A.. In the untrained population, sustained handgrip was accompanied by significant vasodilatation by 75% fatigue in the resting contralateral forearm, with a conductance increase from 0.032 " 0.004 to 0.05 " 0.007 Žml miny1 . 100 mly1 mm Hgy1 Ž P - 0.05. at 100% ŽFig. 1C.. By contrast, trained subjects showed no change in forearm vascular conductance Žrest 0.053 " 0.01, fatigue 0.052 " 0.01 Žml miny1 . 100 mly1 mm Hgy1 . at any stage during the isometric handgrip test. After a 5-week period of training, time to fatigue was not significantly changed Ž105 " 9 cf 111 " 15 s.. The previously untrained subjects showed a substantial degree of attenuation of both heart rate Žrest 75 " 4, fatigue 94 " 5.4 cf. rest 73 " 3.4, fatigue 107 " 3.9 beat miny1 , P - 0.05., and mean arterial blood pressure responses Žrest 92 " 3.2, fatigue 131 " 2.0 cf. rest, 96 " 1.6, fatigue 141 " 3.3 mm Hg, P - 0.05. relative to the pre-training situation ŽFig. 1D and E.. Training also abolished the vasodilator response that was previously seen in the resting limb
pre-training Žrest 0.062 " 0.02, fatigue 0.071 " 0.02 Žml miny1 . 100mly1 mm Hgy1, Fig. 1F.. 3.3. Mental arithmetic In response to mental arithmetic, trained subjects showed no significant increase in heart rate over time, and a 2-min value that was significantly lower than in the untrained group Žtrained 70 " 3.8 cf. untrained 85 " 5.0 beat miny1 , P - 0.05.. The blood pressure response tends to be decreased in the trained population, but reached significance only for diastolic pressure response at 1 min Ž P - 0.05, Fig. 2B.. Mental arithmetic was immediately accompanied by an increase in conductance by 30 s Ž0.028 " 0.003 to 0.006 " 0.015 Žml miny1 . 100mly1 mm Hgy1 , P - 0.05. and remained vasodilated until the end of the mental stress test Žfrom 0.028 " 0.003 to 0.04 " 0.006 Žml miny1 . 100mly1 mm Hgy1 , P - 0.05.. Again, no change was seen in the trained group in vascular conductance at any time during the mental arithmetic challenge ŽFig. 3C..
Fig. 3. Mean " S.E.M. mean arterial pressure, heart rate and forearm vascular conductance at rest and after 2-min mental arithmetic in fit Žopen circle. and unfit Žclosed square. subjects, and post-training Žclosed circle.. Both the fit and post-training group showed a significantly blunted response to mental arousal. Mental arousal was associated with forearm vasodilation in the unfit group, but not in the fit or post-training groups. ) Denotes a significant difference between groups. §Denotes a significant rise from rest.
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Fig. 4. Mean " S.E.M. mean arterial pressure, heart rate and forearm vascular conductance at rest and after 2-min cold exposure in fit Žopen circle. and unfit Žclosed square. subjects, and post-training Žclosed circle.. Fit subjects had a reduced blood pressure response to the cold pressor test. Short-term training had no effect on cold pressor responses. ) Denotes a significant difference between groups. §Denotes a significant rise from rest.
After 5 weeks of training, as with the trained population, mental arithmetic was not accompanied by a significant increase in heart rate, although individual variation in the magnitude of responses meant that the end value reached was not significantly lower than pre-training ŽFig. 3E.. The mean arterial pressure response was significantly reduced Žrest 93 " 3.2, 2 min 105 " 3.2 cf. rest 93 " 1.7, 2 min 114 " 2.8 mm Hg, P - 0.05., and this was due mainly to a reduced systolic pressure ŽFig. 2E, P - 0.05.. As with the sustained handgrip test, the forearm vasodilator response previously noted in untrained subjects, was absent after short-term training ŽFig. 3F.. 3.4. Cold pressor test Two-minute exposure of one foot to iced water had no significant effect on heart rate in either trained or untrained groups, but did cause a significant rise in mean arterial blood pressure. This rise in blood pressure was significantly blunted in the trained population Žuntrained 24 mm Hg increase, trained 13 mm Hg increase, P - 0.05, Fig. 4A.. and was due to a reduced elevation of diastolic pressure ŽFig. 2C, P - 0.05.. Despite this attenuated pres-
sor response, the degree of forearm vasoconstriction in response to cold was similar for both groups ŽFig. 4C.. In contrast to the previous tests, there was no change in the cardiovascular responses to cold exposure after training ŽFig. 4D and E.. 4. Discussion This study evaluated cardiovascular responses to several stressors in chronically trained and untrained men and compared the differences with those produced by a shortterm training programme. We found that subjects with a high degree of pre-existing fitness exhibited reduced tachycardic and pressor responses to handgrip exercise, mental arithmetic and the cold pressor test when compared with age-matched untrained subjects. Additionally, trained subjects showed reduced forearm dilator responses during handgrip exercise and mental stress. After short-term training of the previously untrained population, heart rate, blood pressure and forearm dilator responses were reduced to a similar extent as was seen with chronic training. The pressor and tachycardic responses to isometric exercise are thought to be initiated both from muscle
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chemoreceptors and by central command ŽLind et al., 1964.. Several studies have reported reduced pressor responses to isometric exercise following training involving the same muscle groups as used to initiate the response ŽFleck and Dean, 1987; Somers et al., 1992. and it has been suggested that the effect of training is to reduce muscle chemoreceptor activation ŽSomers et al., 1992.. However, previous studies by our group ŽO’Sullivan and Bell, 2000. and from other laboratories ŽLonghurst et al., 1980. have also shown a blunted heart rate response to handgrip exercise in endurance-trained subjects. In addition, this present study demonstrates blunting of both cardiac and pressor components after only a short programme of cycle ergometry training at a moderate workload. This suggests that training-induced alterations of the exercise pressor reflex need not involve the same muscle groups that undertake the test contraction. In agreement with this, Fisher and White Ž1999. recently reported that after one-legged training, there is similar attenuation of pressor responses to isometric exercise performed in either the trained or untrained limb. It seems likely, therefore, that the blunting effect of training occurs at a higher level than the peripheral sensory inputs. In line with our data, several studies employing microneurography have reported that increased aerobic and forearm exercise training can be associated with reduced muscle sympathetic nerve activity ŽMSNA. responses to isometric exercise ŽRay and Hume, 1998.. In contrast, Seals Ž1991. found no difference in either the pressor or MSNA response to sustained forearm contraction between fit and unfit subjects. The Seals study utilised only 30% maximum voluntary contraction and the small pressor responses produced with this low intensity exercise may not have been sufficient to reveal any group difference. Furthermore, since no information was given on the duration of contraction, this might not have been sufficient to elicit a maximal sympathetic response. In our experience, differences in pressor effects of handgrip between fit and unfit subjects become most pronounced as the fatigue stage is reached. In agreement with our hypothesis that training decreases pressor responses non-specifically, a similar degree of blunting of blood pressure and heart rate responses to mental arithmetic as to sustained handgrip was seen in trained subjects. Nonetheless, there does appear to be some differences between exercise-linked and exercise-independent stimuli, since short-term training did not affect responses to mental arousal to the same extent as in the chronically trained group, while both training duration were equally effective in blunting responses to handgrip. Somewhat similar findings have been reported elsewhere. de Gues et al. Ž1990. found some relationship between fitness levels and diastolic blood pressure responses to coping tasks, but reported no effect on these after 7-week training. Similarly, Steptoe et al. Ž1990. noted a tendency for reduced heart rate reactivity in fitter individuals, but
failed to find any effect of 10-week training on stress reactions. Interestingly, we found that the cold pressor reflex response was less affected by training than either of the other stressors studied. Although the trained group showed a reduced pressor effect of cold exposure relative to that of the untrained subjects, similar blunting of this response was not seen after short-term training. It may be that the degree of adaptation is less after 5 weeks of training than in the chronically trained individuals and that this adaptation may be overridden by a high-intensity sensory input. Alternatively, since sympathetic activation during both exercise and mental arithmetic is initiated from the cerebral cortex, while afferent information from cutaneous cold receptors enters the hypothalamus directly, another interpretation of our findings could be that the adaptive effects of training on sympathetic drive occur preferentially at a supra-hypothalamic level. Bilateral vasodilatation in limb skeletal muscle is well documented as occurring during cerebral arousal ŽBlair et al., 1959; Allwood et al., 1959; Fencl et al., 1959; Dietz et al., 1994.. More recently, a vasodilator response has also been shown to occur in the contralateral forearm musculature during isometric handgrip exercise ŽEklund and Kaijser, 1976; Dietz et al., 1997.. It has been suggested that the dilatation occurring in a resting limb is due to unintended muscle contractions ŽCotzias and Marshall, 1993; Jacobsen et al., 1994.. In the present study, however, we do not believe this to have been a factor, since we observed no movement artefacts on the venous plethysmography record Ždata not shown.. Thus, we believe that the blood flow increases we observed were independent of local metabolic factors. Substantial controversy exists as to whether the increased blood flow seen during handgrip exercise and mental arousal is due to active neural sympathetically mediated vasodilation Žsee Joyner and Halliwill, 2000.. In both situations, studies using b-adrenoceptor blockade have suggested that adrenomedullary activation may be involved ŽBarcroft et al., 1960; Eklund and Kaijser, 1976; Halliwill et al., 1997; Joyner and Halliwill, 2000.. The involvement of sympathetic neural activation was demonstrated by the absence of vasodilation in patients who had undergone sympathectomy ŽBlair et al., 1959.. Furthermore, atropine has been found to abolish the vasodilator response in a number of studies, supporting the involvement of cholinergic fibres ŽBlair et al., 1959; Fencl et al., 1959; Sanders et al., 1989; Dietz et al., 1994, 1997.. The most recent of these are also found inhibitors of endothelial nitric oxide production to reduce the dilator response ŽDietz et al., 1994, 1997.. Despite this, recent findings suggest that the release of nitric oxide may be locally induced, rather than in response to cholinergic stimulation ŽReed et al., 2000; Joyner and Halliwill, 2000.. In the present study, we have found for the first time that trained subjects showed no change in forearm vascular
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resistance during either mental arousal or sustained handgrip exercise. Similarly, both dilator responses were abolished post-training in the previously untrained population. While our data shed no light on the mechanisms involved, this suggests that training is associated with reduced sympathetic vasodilation in situations that are both related and unrelated to exercise. This finding is of considerable interest in relation to control of muscle perfusion during exercise. The dilator response to mental arousal has been interpreted widely as being in anticipation of motor movement; and suggested to optimise intramuscular blood delivery during the first seconds of contraction, prior to the onset of metabolic dilatation Žsee Folkow and Neil, 1971; Bell, 1983.. By contrast, our observations of an inverse relationship between dilator responsiveness and fitness casts, doubt on dilator processes being important for optimal muscle blood flow either during exercise or at its onset, at least in trained individuals. Interestingly, despite the attenuated pressor response to cold in trained individuals, the magnitude of forearm vasoconstriction was similar in trained and untrained groups. It is possible that the central pathway involved in the sympathetic outflow to forelimb skin is separate from the mediating changes in total peripheral resistance. Animal studies have shown that sympathetic vasoconstrictor outflows to different vascular beds have distinct patterns of coupling to specific afferent pathways. For instance, systemic hypercapnea and activation of visceral nociceptors both excite muscle constrictor neurons but inhibit those supplying cutaneous vessels, while vasoconstriction in response to arterial baroreflex withdrawal is powerful in muscle but almost absent in skin Žsee Janig, 1982.. Nevertheless, it is ¨ difficult to see how such a pattern of specificity could explain the lack of blunting of skin vasoconstriction in the presence of a blunted pressor response, since the increase of total peripheral resistance associated with cold exposure is accepted as being primarily localised to the cutaneous vasculature. In summary, we have demonstrated that sympathetic arousal in response to both exercise-related and -unrelated stimuli is blunted in trained, normotensive individuals and that a similar degree of blunting can be induced in untrained subjects by a programme of moderate exercise lasting only a few weeks. We have also shown that training blunts the muscle vasodilator response that normally accompanies isometric exercise and mental arousal, suggesting that this response may not be important in optimising muscle perfusion during or in anticipation of exercise.
Acknowledgements We would like to thank Dr. Susanna Gaynor for her assistance with medical screening, and all our subjects for
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their participation in the study. S.E. O’Sullivan acknowledges the financial support of the Ussher Fellowship postgraduate award.
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Janig, W., 1982. An idea about the organisation of the lumbar sympa¨ thetic outflow supplying skeletal muscle and skin. Proc. Aust. Physiol. Pharmacol. Soc. 13, 47–58. Joyner, M.J., Halliwill, J.R., 2000. Sympathetic vasodilation in human limbs. J. Physiol. ŽLondon. 526, 471–480. Kingwell, B.A., Dart, A.M., Jennings, G.L., Korner, P.I., 1992. Exercise training reduces the sympathetic component of the blood pressure–heat rate baroreflex in man. Clin. Sci. 82, 357–362. Lind, A.R., Taylor, S.H., Humphreys, P.W., Kennelly, B.M., Donald, K.W., 1964. The circulatory effects of sustained voluntary contraction. Clin. Sci. 27, 229–244. Longhurst, J.C., Kelly, A.R., Gonyea, W.J., Mitchell, J.H., 1980. Cardiovascular responses to static exercise in distance runners and weight lifters. J. Appl. Physiol. 49, 676–683. Negrao, C.E., Irigoyen, M.C., Moreira, E.D., Brum, P.C., Freire, C.E., Krieger, E.M., 1993. Effect of exercise training on RSNA, baroreflex control and blood pressure responsiveness. Am. J. Physiol. 265, R365–R370. O’Sullivan, S.E., Bell, C., 2000. The effects of exercise and training on human cardiovascular reflex control. J. Auton. Nerv. Syst. 81, 16–24. Plowman, S.A., Smith, D.L., 1997. Exercise Physiology for Health, Fitness and Performance. Allyn and Bacon, Boston. Ray, C.A., Hume, K.M., 1998. Sympathetic neural adaptations to exercise
training in humans: insights from microneurography. Med. Sci. Sports Exercise 30, 387–391. Reed, A.S., Tschakovsky, M.E., Minson, C.T., Halliwill, J.R., Torp, K.D., Nauss, L.A., Joyner, M.J., 2000. Skeletal muscle vasodilatation during sympathoexcitation is not neurally mediated in humans. J. Physiol. ŽLondon. 525, 253–262. Sanders, J.S., Mark, A.L., Ferguson, D.W., 1989. Evidence for cholinergically mediated vasodilatation at the beginning of isometric exercise in humans. Circulation 79, 815–824. Scheuer, J., Tipton, C.M., 1977. Cardiovascular adaptations to physical training. Annu. Rev. Physiol. 39, 221–251. Seals, D.R., 1991. Sympathetic neural adjustments to stress in physically training and untrained subjects. Hypertension 17, 36–43. Somers, V.K., Leo, K.C., Shields, R., Clary, M., Mark, A.L., 1992. Forearm endurance training attenuates sympathetic nerve response to isometric handgrip in normal humans. J. Appl. Physiol. 72, 1039– 1043. Steptoe, A., Moses, J., Mathews, A., Edwards, S., 1990. Aerobic fitness, physical activity, and psychophysiological reactions to mental tasks. Psychophysiology 27, 264–274. Winder, W.W., Hagberg, J.M., Hickson, R.C., Ehsani, A.A., McLane, J.A., 1978. Time course of sympathoadrenal adaptations to endurance training in man. J. Appl. Physiol. 45, 370–374.
Training reduces autonomic cardiovascular responses to both exercise-dependent and -independent stimuli in humans Saoirse E. O’Sullivan) , Christopher Bell Department of Physiology, Trinity College Dublin, Dublin 2, Ireland Received 5 December 2000; received in revised form 13 February 2001; received in revised form 23 April 2001; accepted 26 April 2001
Abstract Training attenuates the sympathetic pressor response to dynamic exercise. However, it is uncertain how training alters other patterns of cardiovascular autonomic activation. Therefore, we have quantified circulatory responses to a series of standard autonomic tests in highly fit and unfit subjects and examined the effects of a short-term training programme on these responses. Subjects were defined as either unfit Ž n s 8. or fit Ž n s 8. on the basis of training history and a maximal fitness test ŽVO 2peak 54 " 2.3 cf. 68 " 2.8 Žml miny1 . kgy1 , means" S.E.M., P - 0.05.. On a separate day, the blood pressure, heart rate and forearm vascular conductance responses to a sustained handgrip to fatigue, 2 min mental arithmetic and 2 min of cold exposure were measured. All stimuli were associated with elevated blood pressures and heart rates, but these responses were significantly attenuated in the trained group. In the untrained subjects, forearm vascular conductance increased during exercise Žfrom 0.032 " 0.004 to 0.05 " 0.007 Žml miny1 . 100 mly1 mm Hgy1 , P - 0.05. and during mental arithmetic Žfrom 0.028 " 0.003 to 0.04 " 0.006 Žml miny1 . 100 mly1 mm Hgy1 , P - 0.05., but trained subjects showed no rise in conductance during either test. All untrained subjects undertook a moderate intensity 5-week training programme, which significantly increased VO 2peak Ž54 " 2.3 to 57 " 2 Žml miny1 . kgy1, P - 0.05.. Qualitatively similar blunting of pressor, tachycardic and vasodilator responses were seen in this group post-training. These results demonstrate that the blunting of sympathetic vasomotor activation that follows training is not restricted to reflexes associated with exercise, and does not depend on training being prolonged or intense. q 2001 Elsevier Science B.V. All rights reserved. Keywords: Sympathetic activity; Training; Mental stress; Heart rate; Blood pressure; Muscle blood flow
1. Introduction Chronic training is associated with lower exercise heart rates at any given workload ŽScheuer and Tipton, 1977.. This has been attributed in part to a reduced sympathetic pressor response, evident by decreased plasma catecholamines ŽBarnard, 1975; Scheuer and Tipton, 1977; Winder et al., 1978. and decreased muscle sympathetic nerve activity ŽRay and Hume, 1998.. Regular training also leads to resting bradycardia, which is cited as being due to an alteration in autonomic control; increased parasympathetic activity, decreased sympathetic activity or a combination of both ŽScheuer and Tipton, 1977.. Chronic training is also associated with reduced resting blood pressure, which may also involve reduced resting sympathetic nervous activity; however, this issue
)
Corresponding author. Tel.: q353-1608-3545; fax: q353-1608-3545. E-mail address: [email protected] ŽS.E. O’Sullivan..
remains equivocal. Evidence which suggests reduced sympathetic output with training includes decreased plasma catecholamines, catecholamine spillover and muscle sympathetic nerve activity ŽScheuer and Tipton, 1977; Barnard, 1975; Grassi et al., 1994; Huonker et al., 1996.. However, several other studies have reported no change in sympathetic nerve activity with training ŽSeals, 1991; Ray and Hume, 1998.. In addition to the possible effects of training on both exercise and resting sympathetic activity, the sympathetic component of baroreflex control may be altered after training. A reduced cardiac sympathetic response to depressor doses of nitroprusside ŽKingwell et al., 1992. and greater reductions in heart rate and muscle sympathetic nerve activity to pressor doses of phenylephrine ŽGrassi et al., 1994. have been observed post-training. Comparable effects have been shown after training in animal studies, wherein the baroreflex response of renal sympathetic nerve activity is decreased ŽDiCarlo and Bishop, 1988; Negrao et al., 1993..
1566-0702r01r$ - see front matter q 2001 Elsevier Science B.V. All rights reserved. PII: S 1 5 6 6 - 0 7 0 2 Ž 0 1 . 0 0 2 8 8 - 0
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We have previously observed that reflex heart rate responses to the Valsalva manoeuvre and to standing are altered in magnitude in athletes ŽO’Sullivan and Bell, 2000.. However, some investigators have not found training to have an effect on the cardiovascular responses to stimuli such as a cold pressor test or isometric exercise ŽSeals, 1991.. Therefore, the aim of this experiment was to revisit the notion that training affects cardiovascular control, with the hypothesis that autonomic control is affected in a non-specific, exercise-independent manner. To test this, we have assessed the effect of different levels of fitness on blood pressure, heart rate and forearm conductance responses to a series of standard autonomic reflex tests. The tests chosen were a sustained handgrip, mental arithmetic and the cold pressor test. While all three of these stimuli evoke sympathetically mediated rises in total peripheral resistance and blood pressure, they exert differential effects on the other parameters measured. Collectively, these tests allow evaluation of a variety of central sympathetic pathways, carrying information both linked to and independent of those conveying the somatic information associated with exercise. In addition to crosssectional data, we have studied the effects of training on autonomic control longitudinally in previously unfit subjects who underwent a moderate intensity, short-term exercise programme.
2. Materials and methods 2.1. Subjects Sixteen healthy male subjects Ž21–30 years. were recruited on the basis of performing Ž n s 8., or not performing Ž n s 8., regular physical training more than three timesrweek. Height and body masses were recorded and subjects underwent a medical examination to ensure that there were no contraindications to maximal exercise. There was one smoker Ž10rday. in each of the groups. The aims and procedures of the study were explained both orally and in a written document. Subjects signed an informed consent form before testing. All procedures were approved in advance by the Federated Dublin Voluntary Hospitals and St. James’ Hospital Research Ethics Committee. 2.2. Experimental protocol Subjects were required initially to attend the laboratory on two occasions. They were instructed to abstain from caffeine, alcohol, nicotine and exercise for 12 h before an experimental session, in an effort to reduce any effect of stimuli on the cardiovascular system. All testing took place between 0900 and 1300 h at an ambient temperature of 208C. Session 1 comprised of a medical examination, followed by a maximal oxygen consumption incremental exercise test to quantify fitness level. Subjects were also
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familiarised with the experimental procedure for the stress tests during this session. They then reported on a second day for testing, wherein the heart rate, blood pressure and forearm blood flow responses to sustained handgrip, mental arousal and cold exposure were measured. 2.3. Maximal fitness testing Each subject performed a standard incremental fitness test on a Monark 824E cycle ergometer to measure peak oxygen consumption ŽVO 2peak .. The test procedure was explained beforehand and subjects were instructed to continue exercising until exhaustion. The test consisted of 3-min increments beginning at 60 W and increasing by 30 W every 3 min. Heart rate ŽPolar Electro, Finland. and blood lactate concentration ŽYellow Springs Instruments, Ohio. were measured during the last minute of each workload. Metabolic parameters were measured continuously using a Metalyser gas analysis system ŽCORTEX Biophysik, Germany., which was calibrated daily. VO 2peak was taken as the peak oxygen consumption value was reached. 2.4. Sympathetic actiÕation testing During the testing session, subjects were seated comfortably in an upright position. A standard frontal plane ECG was recorded continuously via a MacLab data acquisition system and displayed together with beat-to-beat heart rate. Forearm blood flow was measured continuously in the non-dominant limb by venous occlusion plethysmography, using a gallium–indium strain gauge ŽMedaSonics, Newark. and inflation of an occlusion cuff on the upper arm to a pressure of 40 mm Hg for 4 s every 14 s. Arterial pressure was measured by auscultation from the brachial artery, using phase V Korotkoff sounds as diastolic pressure. The investigator measuring blood pressure was blinded to the training status of the subjects. Mean arterial pressure was calculated as one-third systolic pressure plus two-thirds diastolic pressure. Forearm vascular conductance was calculated by dividing forearm blood flow by mean arterial pressure. Subjects rested for 10 min before the onset of the experiment and initial baseline values for all parameters were obtained at the end of this period. The subjects were then required to perform each of the following tests in turn. Care was taken to ensure all parameters had returned to a stable baseline before presentation of the next stimulus. Ža. Sustained handgrip: Using a handgrip dynamometer, sustained isometric contraction of the dominant hand was maintained at 50% of maximum voluntary contractile force until volitional fatigue. A visual display of the force developed was provided to assist the subject to maintain the appropriate contraction. Žb. Mental arithmetic: Subjects were instructed to continuously subtract the number seven from a three-digit number as quickly and accurately as
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Table 1 Physical and resting cardiovascular characteristics of fit and unfit subjects, and before and after training Fit Height Žcm. Body mass Žkg. BMI Žkg my2 . VO 2 peak ŽŽml miny1 . kgy1 . Heart rate Žbeat miny1 . Mean arterial pressure Žmm Hg. Forearm conductance ŽŽml miny1 . 100 mly1 mm Hgy1 .
Unfit
Post-training
183"2.9 80"3 24"1 68"2.8
177"2.2 75"3.4 24"1 54"2.3 )
74"3.3† 23"1 57"2†
57"3.4 88"2.4
70"3.3 95"1.2 )
67"2.9 92"2.7
0.053"0.01
0.032"0.004
0.062"0.02
possible, for a 2-min period. Žc. Cold pressor test: The right foot was immersed up to the ankle in a basin of iced water Ž2–38C. for 2 min. In parallel experiments, we compared the magnitudes of cardiovascular responses to each test when repeated over several weeks in order to ascertain any habitual effect. No indications were seen on the diminution of responses over time Ždata not shown..
2.5. Training programme Following the initial testing sequence, all untrained subjects underwent a 5-week supervised training programme, consisting of three 30-min sessions per week at 60% VO 2peak on a Monark 824E cycle ergometer. Posttraining, subjects performed a second maximal fitness test and a second series of stress tests. 2.6. Statistical analysis Group results were expressed as means" S.E.M. and were analysed with unpaired Žfor trained versus untrained results. and paired Žfor pre- and post-training, and intragroup over time. Student’s two-tailed t-tests. P - 0.05 was considered significant.
3. Results 3.1. Subject characteristics Physical and resting cardiovascular characteristics of fit and unfit subjects and pre- and post-training are presented
Fig. 1. Mean " S.E.M. mean arterial pressure, heart rate and forearm vascular conductance at rest and 100% fatigue during the sustained handgrip test in fit Žopen circle. and unfit Žclosed square. subjects, and post-Žclosed circle. training, showing the blunting effects of training on the exercise pressor reflex. An increase in forearm vascular conductance in the contralateral arm during isometric exercise was seen in the unfit group, but not in the fit group or post-training. ) Denotes a significant difference Ž P - 0.05, ) ) P - 0.01. between groups. §Denotes a significant increase from resting values.
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in Table 1. There were no significant differences in height, body mass or Body Mass Index between the fit and unfit groups. The subjects recruited as potentially fit had higher VO 2peak values than those in the untrained population, who were regarded sedentary on the basis of the fitness level ŽPlowman and Smith, 1997.. Post-training, previously untrained subjects showed a small Ž5%. but significant increase in fitness typical of 5-week training at the training intensity and frequency undertaken ŽPlowman and Smith, 1997. Žsee Table 1.. Both time to fatigue Ž16.5 "1.2 cf. 19.8 " 1.2 min, P 0.05. and the heart rate at lactate threshold Ž131 " 6 cf. 145 " 3 beat miny1 , P - 0.05. during the fitness test were also significantly improved by training. A small decrease in body mass was seen post-training, but there was no significant change in Body Mass Index. Resting heart rates and blood pressure after the initial rest period were lower in the trained than in the untrained population; however, before each stimulus was presented,
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there was no significant difference in the mean arterial pressure between both groups. Forearm vascular conductance was similar in all groups. Short-term training had no significant effect on the magnitude of any cardiovascular parameter. 3.2. Sustained handgrip There was no significant difference in time to fatigue between fit and unfit subjects Ž121 " 12 cf. 111 " 15 s.. Fig. 1A–C shows the cardiovascular responses of trained and untrained populations to the sustained handgrip test. In both groups, there were progressive elevation of heart rate and blood pressure. However, the magnitudes of these responses were significantly higher in the untrained group, with heart rate increasing by 34 beat miny1 compared with 19 beat miny1 in the trained group Ž P - 0.01, Fig. 1A. and mean arterial pressure rising by 45 mm Hg compared with 29 mm Hg Ž P - 0.05, Fig. 1B.. The reduced pressor
Fig. 2. Mean " S.E.M. systolic and diastolic blood pressure responses over time in fit Žopen circle. and unfit Žclosed square. subjects, and post-training Žclosed circle. during the sustained handgrip, mental arithmetic, and cold pressor test. Fit individuals tended to have lower diastolic pressure values during each test. Post-training, both the systolic and diastolic pressure responses to isometric exercise was reduced, but during mental stress, only systolic blood pressure was affected. ) Denotes a significant difference between groups.
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response of trained subjects involved, decreases in both diastolic and systolic limits ŽFig. 2A.. In the untrained population, sustained handgrip was accompanied by significant vasodilatation by 75% fatigue in the resting contralateral forearm, with a conductance increase from 0.032 " 0.004 to 0.05 " 0.007 Žml miny1 . 100 mly1 mm Hgy1 Ž P - 0.05. at 100% ŽFig. 1C.. By contrast, trained subjects showed no change in forearm vascular conductance Žrest 0.053 " 0.01, fatigue 0.052 " 0.01 Žml miny1 . 100 mly1 mm Hgy1 . at any stage during the isometric handgrip test. After a 5-week period of training, time to fatigue was not significantly changed Ž105 " 9 cf 111 " 15 s.. The previously untrained subjects showed a substantial degree of attenuation of both heart rate Žrest 75 " 4, fatigue 94 " 5.4 cf. rest 73 " 3.4, fatigue 107 " 3.9 beat miny1 , P - 0.05., and mean arterial blood pressure responses Žrest 92 " 3.2, fatigue 131 " 2.0 cf. rest, 96 " 1.6, fatigue 141 " 3.3 mm Hg, P - 0.05. relative to the pre-training situation ŽFig. 1D and E.. Training also abolished the vasodilator response that was previously seen in the resting limb
pre-training Žrest 0.062 " 0.02, fatigue 0.071 " 0.02 Žml miny1 . 100mly1 mm Hgy1, Fig. 1F.. 3.3. Mental arithmetic In response to mental arithmetic, trained subjects showed no significant increase in heart rate over time, and a 2-min value that was significantly lower than in the untrained group Žtrained 70 " 3.8 cf. untrained 85 " 5.0 beat miny1 , P - 0.05.. The blood pressure response tends to be decreased in the trained population, but reached significance only for diastolic pressure response at 1 min Ž P - 0.05, Fig. 2B.. Mental arithmetic was immediately accompanied by an increase in conductance by 30 s Ž0.028 " 0.003 to 0.006 " 0.015 Žml miny1 . 100mly1 mm Hgy1 , P - 0.05. and remained vasodilated until the end of the mental stress test Žfrom 0.028 " 0.003 to 0.04 " 0.006 Žml miny1 . 100mly1 mm Hgy1 , P - 0.05.. Again, no change was seen in the trained group in vascular conductance at any time during the mental arithmetic challenge ŽFig. 3C..
Fig. 3. Mean " S.E.M. mean arterial pressure, heart rate and forearm vascular conductance at rest and after 2-min mental arithmetic in fit Žopen circle. and unfit Žclosed square. subjects, and post-training Žclosed circle.. Both the fit and post-training group showed a significantly blunted response to mental arousal. Mental arousal was associated with forearm vasodilation in the unfit group, but not in the fit or post-training groups. ) Denotes a significant difference between groups. §Denotes a significant rise from rest.
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Fig. 4. Mean " S.E.M. mean arterial pressure, heart rate and forearm vascular conductance at rest and after 2-min cold exposure in fit Žopen circle. and unfit Žclosed square. subjects, and post-training Žclosed circle.. Fit subjects had a reduced blood pressure response to the cold pressor test. Short-term training had no effect on cold pressor responses. ) Denotes a significant difference between groups. §Denotes a significant rise from rest.
After 5 weeks of training, as with the trained population, mental arithmetic was not accompanied by a significant increase in heart rate, although individual variation in the magnitude of responses meant that the end value reached was not significantly lower than pre-training ŽFig. 3E.. The mean arterial pressure response was significantly reduced Žrest 93 " 3.2, 2 min 105 " 3.2 cf. rest 93 " 1.7, 2 min 114 " 2.8 mm Hg, P - 0.05., and this was due mainly to a reduced systolic pressure ŽFig. 2E, P - 0.05.. As with the sustained handgrip test, the forearm vasodilator response previously noted in untrained subjects, was absent after short-term training ŽFig. 3F.. 3.4. Cold pressor test Two-minute exposure of one foot to iced water had no significant effect on heart rate in either trained or untrained groups, but did cause a significant rise in mean arterial blood pressure. This rise in blood pressure was significantly blunted in the trained population Žuntrained 24 mm Hg increase, trained 13 mm Hg increase, P - 0.05, Fig. 4A.. and was due to a reduced elevation of diastolic pressure ŽFig. 2C, P - 0.05.. Despite this attenuated pres-
sor response, the degree of forearm vasoconstriction in response to cold was similar for both groups ŽFig. 4C.. In contrast to the previous tests, there was no change in the cardiovascular responses to cold exposure after training ŽFig. 4D and E.. 4. Discussion This study evaluated cardiovascular responses to several stressors in chronically trained and untrained men and compared the differences with those produced by a shortterm training programme. We found that subjects with a high degree of pre-existing fitness exhibited reduced tachycardic and pressor responses to handgrip exercise, mental arithmetic and the cold pressor test when compared with age-matched untrained subjects. Additionally, trained subjects showed reduced forearm dilator responses during handgrip exercise and mental stress. After short-term training of the previously untrained population, heart rate, blood pressure and forearm dilator responses were reduced to a similar extent as was seen with chronic training. The pressor and tachycardic responses to isometric exercise are thought to be initiated both from muscle
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chemoreceptors and by central command ŽLind et al., 1964.. Several studies have reported reduced pressor responses to isometric exercise following training involving the same muscle groups as used to initiate the response ŽFleck and Dean, 1987; Somers et al., 1992. and it has been suggested that the effect of training is to reduce muscle chemoreceptor activation ŽSomers et al., 1992.. However, previous studies by our group ŽO’Sullivan and Bell, 2000. and from other laboratories ŽLonghurst et al., 1980. have also shown a blunted heart rate response to handgrip exercise in endurance-trained subjects. In addition, this present study demonstrates blunting of both cardiac and pressor components after only a short programme of cycle ergometry training at a moderate workload. This suggests that training-induced alterations of the exercise pressor reflex need not involve the same muscle groups that undertake the test contraction. In agreement with this, Fisher and White Ž1999. recently reported that after one-legged training, there is similar attenuation of pressor responses to isometric exercise performed in either the trained or untrained limb. It seems likely, therefore, that the blunting effect of training occurs at a higher level than the peripheral sensory inputs. In line with our data, several studies employing microneurography have reported that increased aerobic and forearm exercise training can be associated with reduced muscle sympathetic nerve activity ŽMSNA. responses to isometric exercise ŽRay and Hume, 1998.. In contrast, Seals Ž1991. found no difference in either the pressor or MSNA response to sustained forearm contraction between fit and unfit subjects. The Seals study utilised only 30% maximum voluntary contraction and the small pressor responses produced with this low intensity exercise may not have been sufficient to reveal any group difference. Furthermore, since no information was given on the duration of contraction, this might not have been sufficient to elicit a maximal sympathetic response. In our experience, differences in pressor effects of handgrip between fit and unfit subjects become most pronounced as the fatigue stage is reached. In agreement with our hypothesis that training decreases pressor responses non-specifically, a similar degree of blunting of blood pressure and heart rate responses to mental arithmetic as to sustained handgrip was seen in trained subjects. Nonetheless, there does appear to be some differences between exercise-linked and exercise-independent stimuli, since short-term training did not affect responses to mental arousal to the same extent as in the chronically trained group, while both training duration were equally effective in blunting responses to handgrip. Somewhat similar findings have been reported elsewhere. de Gues et al. Ž1990. found some relationship between fitness levels and diastolic blood pressure responses to coping tasks, but reported no effect on these after 7-week training. Similarly, Steptoe et al. Ž1990. noted a tendency for reduced heart rate reactivity in fitter individuals, but
failed to find any effect of 10-week training on stress reactions. Interestingly, we found that the cold pressor reflex response was less affected by training than either of the other stressors studied. Although the trained group showed a reduced pressor effect of cold exposure relative to that of the untrained subjects, similar blunting of this response was not seen after short-term training. It may be that the degree of adaptation is less after 5 weeks of training than in the chronically trained individuals and that this adaptation may be overridden by a high-intensity sensory input. Alternatively, since sympathetic activation during both exercise and mental arithmetic is initiated from the cerebral cortex, while afferent information from cutaneous cold receptors enters the hypothalamus directly, another interpretation of our findings could be that the adaptive effects of training on sympathetic drive occur preferentially at a supra-hypothalamic level. Bilateral vasodilatation in limb skeletal muscle is well documented as occurring during cerebral arousal ŽBlair et al., 1959; Allwood et al., 1959; Fencl et al., 1959; Dietz et al., 1994.. More recently, a vasodilator response has also been shown to occur in the contralateral forearm musculature during isometric handgrip exercise ŽEklund and Kaijser, 1976; Dietz et al., 1997.. It has been suggested that the dilatation occurring in a resting limb is due to unintended muscle contractions ŽCotzias and Marshall, 1993; Jacobsen et al., 1994.. In the present study, however, we do not believe this to have been a factor, since we observed no movement artefacts on the venous plethysmography record Ždata not shown.. Thus, we believe that the blood flow increases we observed were independent of local metabolic factors. Substantial controversy exists as to whether the increased blood flow seen during handgrip exercise and mental arousal is due to active neural sympathetically mediated vasodilation Žsee Joyner and Halliwill, 2000.. In both situations, studies using b-adrenoceptor blockade have suggested that adrenomedullary activation may be involved ŽBarcroft et al., 1960; Eklund and Kaijser, 1976; Halliwill et al., 1997; Joyner and Halliwill, 2000.. The involvement of sympathetic neural activation was demonstrated by the absence of vasodilation in patients who had undergone sympathectomy ŽBlair et al., 1959.. Furthermore, atropine has been found to abolish the vasodilator response in a number of studies, supporting the involvement of cholinergic fibres ŽBlair et al., 1959; Fencl et al., 1959; Sanders et al., 1989; Dietz et al., 1994, 1997.. The most recent of these are also found inhibitors of endothelial nitric oxide production to reduce the dilator response ŽDietz et al., 1994, 1997.. Despite this, recent findings suggest that the release of nitric oxide may be locally induced, rather than in response to cholinergic stimulation ŽReed et al., 2000; Joyner and Halliwill, 2000.. In the present study, we have found for the first time that trained subjects showed no change in forearm vascular
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resistance during either mental arousal or sustained handgrip exercise. Similarly, both dilator responses were abolished post-training in the previously untrained population. While our data shed no light on the mechanisms involved, this suggests that training is associated with reduced sympathetic vasodilation in situations that are both related and unrelated to exercise. This finding is of considerable interest in relation to control of muscle perfusion during exercise. The dilator response to mental arousal has been interpreted widely as being in anticipation of motor movement; and suggested to optimise intramuscular blood delivery during the first seconds of contraction, prior to the onset of metabolic dilatation Žsee Folkow and Neil, 1971; Bell, 1983.. By contrast, our observations of an inverse relationship between dilator responsiveness and fitness casts, doubt on dilator processes being important for optimal muscle blood flow either during exercise or at its onset, at least in trained individuals. Interestingly, despite the attenuated pressor response to cold in trained individuals, the magnitude of forearm vasoconstriction was similar in trained and untrained groups. It is possible that the central pathway involved in the sympathetic outflow to forelimb skin is separate from the mediating changes in total peripheral resistance. Animal studies have shown that sympathetic vasoconstrictor outflows to different vascular beds have distinct patterns of coupling to specific afferent pathways. For instance, systemic hypercapnea and activation of visceral nociceptors both excite muscle constrictor neurons but inhibit those supplying cutaneous vessels, while vasoconstriction in response to arterial baroreflex withdrawal is powerful in muscle but almost absent in skin Žsee Janig, 1982.. Nevertheless, it is ¨ difficult to see how such a pattern of specificity could explain the lack of blunting of skin vasoconstriction in the presence of a blunted pressor response, since the increase of total peripheral resistance associated with cold exposure is accepted as being primarily localised to the cutaneous vasculature. In summary, we have demonstrated that sympathetic arousal in response to both exercise-related and -unrelated stimuli is blunted in trained, normotensive individuals and that a similar degree of blunting can be induced in untrained subjects by a programme of moderate exercise lasting only a few weeks. We have also shown that training blunts the muscle vasodilator response that normally accompanies isometric exercise and mental arousal, suggesting that this response may not be important in optimising muscle perfusion during or in anticipation of exercise.
Acknowledgements We would like to thank Dr. Susanna Gaynor for her assistance with medical screening, and all our subjects for
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their participation in the study. S.E. O’Sullivan acknowledges the financial support of the Ussher Fellowship postgraduate award.
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