Interaction of fastigial pressor response and depressor response to nasal perfusion

Journal of the Autonemic Nervous System, 2 (1980) 269--280 © Elsevier/North-Holland Biomedical Press

269

INTERACTION O F FASTIGIAL PRESSOR RESPONSE A N D D E P R E S S O R RESPONSE T O N A S A L PERFUSION

K.J. DORMER and H.L. STONE Department of Physiology and Biophysics, P.O. Box 26901, ~Iniversity of Oklahoma Health Sciences Center, Oklahoma City, Okla. 73190 (U.S.A.) (Received December 3rd, 1979) (Accepted June 17th, 1980)

Keywords: cerebellum -- fas~.,igial nucleus -- trigeminal nerve -- dive response -- barozeceptor ~eflex -- bradycardia -- electrical stimulation -dP/dt -- hypertension

ABSTRACT

The fastigial nucleus pressor response (FPR) and the nasal-perfusion diving response were elicited alone and simultaneously to observe the net effect on cardiovascular variables. The fastigial nucleus was electrically stimulated in 14-chloralose--urethane anesthetized dogs and the FPR was characterized by a transient tachycardia'with sustained elevations in arterial pressure, left ventricular pressure and maximal dP/dt. T h e tachycardia was buffered b y baroreceptor reflexes during the elevated arterial pressure of the FPR. All variables of the FPR, however, were reduced by superimposition of the diving response upon the FPR. Heart rate was most sensitive to depression by the nasal perfusion which elicited a bmdycardia as much as 70 beats/rain below the control rate. The nasal~voked diving response was discussed with respect to the trigeminal depressor response which results from direct stimulation of the spinal trigemin~ complex. Algebraic cancellation of the FPR and dive responses is considered along with anatomical and electrophysiological evidence which suggests t h a t these two responses, as well as the baroreceptor reflex, could be integrated at a c o m m o n site. This site may be the medullary nucleus of the solitary tract which receives projections from trigeminal and glossopha~mgeal nerves and from the fastigial nucleus.

270 INTRODUCTION The cardiovascular response to electrical stimulation in rostro-medial portions of the cerebellar fastigial nucleus (FN) is a powerful sympathetically mediated response characterized by elevated he&~t rate, left ventricular and arterial pressures, left ventricular dP/dtmax and coronary blood flow [9,10, 22]. These changes which resemble barol~ceptor unloading are for the most part directly opposite to the physiological changes observed during diving in aquatic birds and mammal~ [2] and terrestrial vertebrates including man [5, 12]. It is not surprising that the fastigial pressor response (FPR) and the diving response are both elicited by afferent projections to medullary areas influencivg control of the cardiovascular system; however, both of these afferent projections innervate at least one nucleus in common, the nucleus of the solitary tract (NTS). The NTS is the primary afferent relay for carotid ~inus baroreceptoi" hffo~ma~ion ar,d may .~,.L~.c~onas an integrator of ascending information regarding heart rate and blood pressure [26]. The dog has been used a~ a model to study cardiorespiratory changes during the diving responses evoked by perfusion of the nas~ passages. Angell-James and Daly [3], using chloralose-~trethane anesthetized dogs, stimulated the nasal mucous membrane by perfusing the nasal passages with water and produced apnea, bradycardia and vasoconstriction in certain vascular beds. Gooden e t al. [12] also observed decreased coronary blood flow and myocardial oxygen consumption in awake dogs during voluntary head submersion. The present st~dy was designed to record the cardiovascular response to a simultaneously evoked dividing response and FPR in the anestheti'.:ed dog. It was reasoned that the net response would provide information about medullary areas svbserving cardiovascular function. The results indicate an algebraic summation of these two opposing responses and suggest a possible interaction of "~dferent neurons prior to the activation of descending autonomic pathways. MATERIALS AND METrlODS Experimen:~ were carried out on 14 mongrel dogs of either sex. An a-chloralose--urethane aqueous mixture (initial dose: chloralose 0.05 g/kg; urethane 0.5 g/kg i.v.) was used for anesthesia following premedication with .~_mg/kg morvhine sulfate. A sub-laryngeal tracheostomy was performed and respiration wP~ usually unassisted. Arterial pressure was monitored by a pressure transducer (Statham P23 Db) connected to a canntfla in the right femoral artery. Metaraminol (Aramine) was injected (1--5 mg i.v.) to elevate arterial pressure without electrical stimulation of the brain. Left ventricular pressure ~LVP) was obtained by retrogradely passing a solid-state catheter tip pressure transducer (Millar Instruments) from the left femoral artery into the left vent~cle. This LVP signal was differentiated to obtain maximal dP/dt which w~~ used as an index of myocardial contractility. The arterial pressure

271

pulse also triggered a cardiotachometer to determine he~,~-trate. Respiratory rate was monitored by inserting a thermistor into the endotracheal tube and recording expiratory temperature fluctuations. All variables were recorded on a chart recorder (Beckman Dynagraph). The diving response was initiated by pumping either room temperature normal saline or tap water (100--500 ml/min) through the nasal passage and nasopharynx. A puisatile pump (Sarns) was connected to two balloon retention catheters (Bardex, 12 F) inserted into the nose for water circulation. The effluent was collected through a pair of balloon 16 F catheters orally inserted i n ~ the nasopharynx and the nasopharynx was evacuated in between diving responses. This modified technique of Angell-James and Daly [3] w ~ used ~o initiate the diving response at 30--50 rain intervals while the dogs were sufficiently but not deeply anesthetized. Concentric bipolar electrodes (Kopf SNE-100) were inserted into rostral portions of the FN using modified steleotaxic techniques for mongrels described elsewhere by Dormer and Stone [10]. Stimulus parameters consisted of 10--15 sec epochs of 80 square wave pulses/sec, 100/asec duration, 100--700/~A of constsnt current (WPI 800 series). The experimental procedure consisted of: (1) electrical activation of the FPR; (2) 5--10 rain later repetition of the FPR during the nasal perfusion diving response; and (3)repetition of the FPR or diving response alone, though not necessarily in the above order. Following each experiment the dogs were sacrificed by injection of KC1. The electrode ~ite was lesioned using DC current (20 V for 30 sec) and the cerebellum wa~ removed and placed in 10% buffered formalirl and 1% potassium ferricyanide. Sections of 30--75 #m were cut and stained with cresyl violet for verification of electrode site. Data were compared using a paired t-test and a P value of less than 0.05 was considered to indicate statistical significance. RESULTS

Stimulation in discrete portions of rostral fastigial nucleus (FN) in the dog initially evoked a sympathetically-mediated increase in heart rate, arterial pressure and left vent~icular dP/dt as describect previously [10]. The tachycardia alone was reduced by baroreceptor reflexes during FN stimulations greater than 3 sec (Fig. 1). After the initial ~achycardia, vagally-mediated reduction in heart rate persisted along with the elevated arterial pressure and dP/dt. Earlier studies have demonstrated a suslained tachycardia during FN stimulation when the carotid sinuses were ~ascularly isolated bilaterally [10]. The pressor response was also buffered t~ a minor degree by the baroreceptor reflex, but this was not readily discernible in the typical fastigial pressor re~ponse (FPR) employed during these experiments. Stiniulus threshold for the FPR was approximately 50/~A and heart rate and arterial pressure linearly increased as current was increased to 1.5 mA.

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Fig. 2. Initial changes in heart rate, mean arterial pressure, left ventricular pressure and d L V P / d t in response to stimulation o f the FN (A), FN stimulaticn plus nasal perfusion (B), and nasal perfusion alone (C). The per cent change in each of the parameters from the preceding control values is shown for the number of events. A two-tailed t-test was performed and the results indicated were significantly different (* P < 0.005; ** P < 0.001). The changes in contractility demonstrated for the first time a negative inotropic effect during the physiological adjustments to diving. Heart rate, however, was most sensitive to the nasal perfusion stimulus.

Submaximal stimuli produced peak tachycardia and pressure rises approaching 290 beats/min and 270 mm Hg respectively, which completely masked any changes resulting from the diving response. No cancellation of the heart rate, arterial pressure or dP/dt changes was observed when a submaximal F P R was evoked during diving. Consequently, only those fastigialresponses exhibiting heart, rate and pressor changes on the order of magnitude of those observed during the diving response were selected for comparison in this exp~ximent. The results of F N stimulation, nasal peffusion and both performed simultaneously are shown in Fig. 2. The initial peak tachycardia during the F P R averaged 31 beats/rain (+3 S.E.) or 27.7 + 2.9% above the mean control rate of 113 + 5 beats/rain in 14 dogs. Nasal perfvsion alone produced a 17 +- 2 % decrease in heart rate representing a 19 ± 2 beats/rain decrease. The largest nasal-evoked bradycazdia decreased the heart rate by 70 beats/rain. Finally, when both the diving and fastigial responses were elicited simultaneously

274

only a 14 -+ 4 % increase in heart rate (16 +- 4 beats/rain) could be elicited. This algebraic summation during both responses was most noticeable in the heart rate change and less so in the other variables observed. If the diving response was elicited first,then both the onset of the F N ~ v o k e d tachycardia and its rate of rise were delayed; however, the fastigialresponse was never comp'ctely supL0ressed. In addition, the bradycardia, which usually followed the b:def initial tachycardia anu which was due to the baroreceptor reflex secondarily evoked by the rise in arterial pressure, was augmented by the addition of a diving response. This augmentation occurred when the arterial pressure rise was relatively minor during the F P R alone. The powerful ,,,agal activation dmdng the diving response [3--5] was demonstrated by initially elevating the mean arterial pressure (MAP) by 40--50 m m Hg with metaraminol infusion. This reduced resting heart rate through baroreceptor reflexes from 150 to 60 beats/rain; nevertheless, nasal perfusion reduced heart rate

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Fig. 3. Fastigial pressor response alone and duri.lg the nasal perfusion diving response. The FN evoked increases in pulsatile and mean arterial pres.,;ure (AP, MAP), left ventricular pressure (LVP), myocardial contractility (dP/d.tmax) and heart rate (HR) are s h o w n for the initial 10 sec of FN stimulaUon at approximately 5x threshold. The relatively m i n o r changes in pressure were insufficient 1o evoke a vagal bradycardia during the latter phases o f FN stimulation, b u t w h e n the diving response was elicited simultaneously during FN stimulation the tachycardia, increased dP/(', ~:,~d .L~ressure rise were overridden. A r r h y t h mias were also n o t e d occasionally followmp .i. .,h :itation o f b o t h responses. ( t indicates the onset of nasal perfusion arid ~ indicates cc .~tion).

275

by an additional 4--5 beats/win. Arterial pressure is a complex variable (dependent upon cardiac output and peripheral resistance) which was affected by both the F P R and diving responses. The M A P increased 23.1 -+ 1.9% during the F P R (Fig. 2). This represents a 33 -+ 3 m m H g increase over control for stimulus currents ranging from 0.5 to 1.2 m A . The diving responses included in this study reduced M A P by 6.8 + 1.4% (--7 -+ 2 m m Hg) and this occurred shnultaneously with the decrease in heart rate; however, rises in pressure as a result of nasal perfusion are included in thesc data. Increases in arterial pressure were frequently observed by Angell-James and Daly [4] and apparently are dependent upon the depth of anesthesia. W h e n both diving an@~FPR responses were elicited simultaneously, the M A P was increased by 16.5% (+1.8 S.E.) which corresponds to an increase of 22 -+ 2 m m Hg. Left ventricular pressure and the first derivative dP/dtmax were both reduced by the diving response but relatively not as m u c h as the heart rate (Fig. 2). L V P was reduced 9.2 + 1.4% representing 13 + 2 m m H g told F N stimulation increased left ventricular pressure 28.3 + 2.3% or 41 -+ 3 m m H g above control pressure. W h e n the diving and F N stimulation responses were elicited simultaneously the pressure increased by only 22.2 ± 2.7% oz 31.5 + 4 m m Hg. These ventricular changes were similar to those of arterialpressure. The changes in contractilitywere more remarkable and demonstrate, to our knowledge for the first time, a decrease in dP/dt associated with this type of diving response. Concomitant with the decreases in heart rate and pressure, dP/dt decreased by 9.5 + 3.4% (or 232 + 77 m m H g sec -I) during nasal perfusion. This adds a new dimension to the cardiac response, possibly decreased sympathetic activity as well as increased parasympathetic activity. This reduction in myocardial contractility,most likely a result of decreased sympathetic activity, partially cancelled the increase in contractility during the FPR. The 36.5 + 3.8% increase in dP/dt (902 ± 94 m m H g sec -I) was reduced to 22 + 3.4% above control levelsor 534 + 82 m m H g sec-~. A few comments can be made on the respiratory changes associated with both of these responses, although the apnea associated with nasal perfusion was not always elicited.Rapi:l, shallow, breathing was often observed during the FPR. This tachypnea increased the respiratory rate from 12/rain to 50 or 60/min so that the endotr~cheal thennister could not follow the rate (Fig. 1). Conversely, we also observed the apnea associated with the diving response [4]. The most dramatic apneic response observed lasted for 90 sec though the nasal perfusion lasted only 13 sec. In most cases, the apnea was short-lived or lasted as long as the nasal perfusion. Evidence suggests that the diving apnea was stronger than the rN-induced tachypnea, but there ~tre insufficient data on the interaction of these two respiratory responses to warrant firm conclusions at this time. Histological studies on the electrodes lesions confirmed the sites eliciting the F P R were located in rostralportion of F N and immediately surrounding white matter. These sites in the mongrel dog are comparable to those described earlier [10].

276

DISCUSSION These results have demonstrated ~he net response from evoking two opposing cardiovascular responses, one essentially physiological, and the other resulting from electrical activation of a fastigio--medullary pathway. Both individual responses were evoked on the same order of magnitude and the interaction between the two was found to be an algebraic summation. Our present knowledge concerning neural control oF the cardiovascular system is typically based on observations where a singlte pathway or reflex has been examined and the possible interaction from other homeostatic mechani:~m~ ignored or eliminated. Nevertheless, most reflex circulatory adjustments are integrated responses resulting from the input of multiple afferent subsystems and affecting the output of several efferent subsystems. The algebrvLic summation of heart rate, blood pressure and contzactility during the diving fastigial nucleus (FN) responses suggests integration may have occurred, particularly since baroreceptor reflexes were also operating during the elevated arterial pressure of the fastigial pressor respon~ (FPR). The site for this potential integration may be proposed based on correlative anatomical studies. Our observations on the diving response confirmed the cardiorespiratory ch~.nges obl~ined by nasal perfusion in earlier studies [3,4,17]. Changes in arterial pressure were variable but pressure usually fell at the onset of perfusion. This initial decline in pressure was compared with the pressor and heart rate changes of the FPR and although the diving depressor response was concomitant with the bradycardia it usually recovered to pressures above control values and wa~ nc,t strictly related to the heart rate changes. Overall, the Ilasal perfusion diving response was depressor and oxygenconserving in nature and thus qualitatively similar to the natural diving response [11]. The 17% reduction in heart rate we observed was probably effective in reducing myocardial oxygen consumption since in voluntarily diving dogs with a decrease in heart rate of 48% coronary blood flow velocity decreased and coronary oxygen, satm'atic,n increased [12]. The other means of oxygen conservation we observed has not been reported previously, and involved reduced myocardial contractility. A 9.5% decrease in dP/dt is noteworthy since heart rate and contractility ar,e two of the major determinants of myocardial oxygen consumption [7]. This decreased contractility may h3.ve been due to either withdrawal of sympathetic drive to the he.art or a vagaUy-mediated negative inotropic effect [15] or perhaps both. The trigeminal ~erve is responsible for eliciting the cardiovascular changes during perfusion of the nasal passages and for the actual diving response in aquatic mamm~ls [2,4,5]. Anderson [2] found that the ophth~hnic branch, in particular, carriPd sensory information during facial immersion which affected change in cardiovascular and re~p~atory activity. Re-section of the trigeminal nerve or application of local anesthetic to the nasal region abolished the divhlg response [3]. Recently, a depressor response has been described from stimulation of peripheral branches of the trigeminal nerve or

277 spinal trigeminal complex [19,20]. This trigeminal depressor response (TDR) revolved a decrease in arterial pressure, bradycardia with apnea, and was remarkably similar to the diving response in that: (1) inhibition of sympathetic nervous system activity caused the depressor response; and (2) bradycardia resulted from both cardiovagal excitation azld sympathetic inhibition. The decrease in dP/dtmax observed in this study during nasal perfusion is also indicative of decreased sympathetic drive to the heart and/or increased parasympathetic actJwity [13]. Kumada et al. [19,20] compared the TDR with the aortic depressor reflex (ADR) and found no significant differences between the two using linear regression analysis. Their evidence suggests that the diving response, aortic depressor response and trigeminal depressor response are utilizing the same efferent cardiac pathways even though the peripheral vascular pathways may differ slightly. The origin of tile efferent cardiac limb of the nasal-evoked diving response is of major interest to us since the heart rate response is opposite during FPR. If the diving response, TDR and ADR vasodepressor responses utilize a common sympathoinhibitory site in the medullary reticular formation and if this site aJso receives projections from FN then this site is a candidate for integration of the FPR and diving responses. This site for possible integration between the cerebellar pressor and nasalevoked depressor responses may also be the site where the b~roreceptor reflex is inhibited during the FPR. Arterial pressure remains elev. ~ted during the FPR as long as baroreceptor pathways remain b~tact [10,22). Such FN interaction would be analogous to hypothalamo--n,edullaxy interaction where the sympathoinhibitory effects of carotid sinus stimulation are inhibited by stimulation within the hypothalamic defense area [8]. As early as 1940 Moruzzi reported anterovermal stimulation inhibited normal baroreceptor f~mction [24] and since then several other studies h~ve confirmed that the cerebellum has autonomic functions as well as motor [1,15,16]. Huang et al. found an unexpected augmentation of the rise in arterial pressure during carotid artery occlusion when FN was lesioned bilaterally in cats. Hence, interaction between the FPR and diving responses may occur at fastigiomedullary projection sites subserving both baroreceptor reflex (carotid sinus nerve) and diving response (trigeminal nerve) afferents. One medullary site which could function as an intet,~ator of the above cardiovascular responses is the nucleus of the solitary tract (NTS). Bilateral lesions of NTS produce a permanent neurogenic hyp~rtension [21] and anatomica~ evidence fl'ora cat and man has implied NTS involvement in the diving, FPP~ and baroreceptor reflex responses. The FN projects to parasolitary regions of NTS (see ref. 10) and receives collateral ~ffferent projections from NTS [27 I. Furthermore, the first relay nucleus of the carotid s.mus and aortic depressor baroreflexes (which axe partially inhibited during the FPR) is the NTS [14,22,26]. In addition to projecting to associated principal and spinal nuclei ~3d to the rostral ventrolateral NTS ~18,28] trigemir~al nerve afferents al,,~o project to the medial ventrolateral pL~rtion of NTS. B~;ckstead and Norgren [6] using autoradiographic techniques in the monkey have

278

shown primary trigeminal, glossopharyngeal and to a lesser extent vagal projections to medial NTS and parasolitary zegions where convergence occurs. The .recent anatomical description of NTS subdivisions confirmed that NTS projections to the lateral reticular formation emanate from the caudal half or two-thirds o~[the NTS [23,25]. Presumably the caudal two-thirds of the NTS are involved in cardiovascular control mechanisms and the rostral third of the nucleus ser~es as a gustatory feeding center. Since the nasal-evoked, trigeminal-mediated depressor response accentuates the bradycardia following FN stimulation and since the depressor--dive response algebraically cancels part of the initial tachycard~a caused by FN stimulation, it is both physiologically and anatomically feasible that the site of integration of these ,3 responses is the NTS. Integration of the diving, FPR and baroreceptor reflex responses would likely occur prior to the subsequent NTS actiwtion of descendhlg ~ardiovagal and depressor pathways in the dorsal and lateral medullary reticular formatic,n. The mode of afferent interaction in the NTS is uwknown at the present time but may be at st~ond order neurons within NTS. The cmdiovascular interactions recorded in this study involved: (1) fastigiomedullary (presser) projections which activated generalized sympathetic nervous system activity; (2) trigeminal afferent projections which were depressor in function; and (3) baroreceptor afferents activated as a result of the FPR, which were depressor in function. The secondarily activated barereceptor reflexes caused vagally~mediated bradycardia during the latter stages of FN stimulation and elevated arterial pressures. Consequently, when the FPR was elicited during a nasal evoked diving response the net response 1--3 sec into the FPR was the integrated effect of trigeminal afferen~s on FN-medullary sympathoexcitatory efferents. At approximately 5--10 sec into tile FPR and the diving response the net effect on the heart also involved meduUary baroreceptor ai'ferents since in the dog the cardiac portion of the FPR was buffered by the baroreceptor reflexes. When the diving depressor and FN presser responses were evoked simultaneously and were relatively equal in magnitude the responses mutually algebraically cancelled. The sugge,,~tion that these two responses were integrated within the NTS is supported by ,~natomical and electrophysiological studies but the presence of trigeminal and baroreceptor afferents and FN efferents within cardiovascular portions of NTS is insuficient evidence to conclude integration has occurred. Another possibility for the site of interaction with hear~ rate responses is the sinoatrial node itself. The net cancellation between the initial tachyc,~"dia of the FPR and diving bradycardia could take place at the sinoatrial node where a combi~,~d v~al--sympathetic effect would mutually cancel. New.~rtheless, since the nasal-evoked div~rAgresponse both cancelled the FN symF.athetic activation and added to the baroreceptor-induced bradycardia durillg the latter stages of the FPR, we conclude that medullary integrative centers were utilized during FN and trigeminal nerve activation.

279 ACKNOWLEDGEMENTS

This work was support~,~lin part by NIH Grants HL05~.45 (Post-Doctoral Fellowship), HS22747 (Young InvestigatorsAward) and b!ASA NSG-2282. W e thank Dr. F.R. Cala~:esufor helpful comments and Miss Sondra Anderson for typing the manuscript. REFERENCES 1 AI-Senawi, D.A.E.-H. and Downman, C.B.B., Cardiac dysrhythmia of fastigialnuclear origin, J. Physiol. (Lond.), 284 (1978) 8 7 - 8 8 P . 2 An derson, H.T., The reflex nature of the physiological adjustments to diving and their afferent pathway, Acta physiol, scand., 58 (1963) 268.--273. 3 Angell-James, J.E. and Dab r, M. deB., Nasal reflexes, Pro.,'. roy. Soc. Med., 62 (1969) 1287--1293. 4 Angell-James, J.E. and Daly, M. deB., Reflex respiratory and caxdiovascalar effects of stimulation of receptors in the nose of the dog, J. Physiol. (Lond.), 220 ( 1 9 7 2 ) 6 7 3 - 696. 5 Angell-James, J.E. and Daly, M. deB., Some mechanisms involved in the cardiovascular adaptations~o diving, Syrup. Soc. exp. Biol., 26 (1972) 313--341. 6 Beckstead, R.M. and Norgven, R., Central distribution of cranial nerves, V, VII, IX and X in the monkey, Neurosci. Abstr., 4 (1978) 85. 7 Braunwald, E., Control of myocardial oxygen consuml~tion, Amer. J. Cardiol., 27 (1971) 416--432. 8 Coote, H., Hilton, S.M. and Perez-Gonzalez, J.F., Inhibition of the baroreceptor reflex on stimulation in the brain stem defense centre, J. Physiol. (Lond.), 288 (1979) 549--560. 9 Dormer, K.J. and Stone, H.L., The effect of clonidine on the fastigial pressor response in dogs. J. Pharm. exp. Ther., 205 (1978) 212--220, 10 Dormer, K.J and Stone, H.L., Cerebellar pressure response in the dog, J. appl. Physiol., 41 (19i :) 574--580. 11 Eisner, R., l~ranklin, D.L., can Citters, R.L. and Kenney, D.W., Cardiovascular defense against asphyxia, Science, 153 (1966) 941--949. 12 Gooden, B.A., Stone, H.L. and Young, S., Cardiac response to snout immersion in trained dogs. J. Physiol. (Lond.), 242 (1974) 405--414. 13 Higgins, C.B., Vatner, S.F. and Braunwald, E., Parasympathetic control of the heart, Pharmacol. Rev. 25 (1973) 120--142. 14 Hilton, S.M., Supramedullary organization of vasomotor control. In W. de Jong, A.P. Provoost and A.P. Shapiro (Eds.), Hypertension and Brain Mechanisms, Progress in Brain Research, Voi. 47, Elsevier, Amsterdam, 1977, pp. 77--84. ~'5 Huang, T.F., Cardiac arrhythmia induced by electrical stimulation of the fastigial nucleus in cats, Jap. J. Physiol., 27 (1977) 565--576. 1~5 Huang, T.F., Carl~,enter, M.B. and Wang, S.C., Fastigial nucleus and orthostatic reflex in the cat and monkey, Amer. J. Physiol., 232 (1977) H676--H681. 17 Kawakami, Y., Natelson, B.H. and Dubois, A.B., Cardiovascular effects of face immersion and factors affecting diving reflex in man, J. appl. Physiol., 23 (1967) 964. 18 Kerr, F.W.L.. Struct:ural relation of the trigeminal spinal tract to upper cervical roots and the solitary nucleus in the cat, Exp. Neurol., 4 (1961) 134--148. 19 Kumada, M., Dampno.y, R.A.L. and Reis, D.J., The trigeminal deprersor response: a novel vasodepressor response orig;nating from the trigemina] system, Brain Res.. 119 (1977) 305--326. 20 Kumada, M., Dampnt.,y, R.A.L., Whitnall, N.H. and Reis, D.J., Hemocynamic similarities between the trigeminal and aortic vasodepressor responses, Ar~ter. J. Physiol., 23~/ (1978) H67--H73.

280 21 Laubie~ M. av,d SchmitL H., Destruction of the nucleus tractus solitarii in the dog: cor:,parison with sino-aortic d~.nervation, Amer. J. Physiol., 336 (1979)I~736--H743. 22 Llsander, B. and Martner, J., Interaction between the fastigial pre~or response and the baroreceptor reflex, Acta physiol, stand., 83 (1971) 505-~514. 23 Loewy, A. an,~ Burton, H., Nuclei of the solitary tract: efferent projections to the lower brain sterr~ and spinal cord of the cat, J. comp. Neurol., 181 (1978) 421--450. 24 ~oruzzi, G, ~'~'., c ~ b c ; l a r inhibition c( vasomotor and respiratory carotid sinus reflexes, J. Nel~-~..hysiol., 3 (1940) 20--32. 25 Norgren, B., .P~'~jections from the nucleus of the solitary tract in the rat, Neuroscience, 3 (197B) 207--218. 26 Pa]kovits, M. and Zabroszky, L., Neuroanatomy of central cardiovascular control. Nucleus tractus solitarii: afferent and efferent neuronal connections in relatior,~ to the baroreceptor refle.~ arc. In W. deJong, A.P. Provoost and A.P. Shapiro (Eds.), ~ttypertension and Brain Mechanisms, Progress in Brain Research, Vol. 47, Elsevier, . ~ s t e r clam, 1977, pp. 9--~4. 27 Somana, R. and "~'alberg, ~'., Cerebellar afferer~ts from the nucleus of the solitary tract, Neurosci. Lett., 11 (1979)41--47. 28 Wailenberg, A., Das dorsal? Gebiet der spinalen Trigeminuswurzel und Beziehungen zum solitaren B u n ~ ! beim ~enschen, Dtsch. Z. Nervenheilk. 11 (1897) 391--405.