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Cardiovascular effects of nitric oxide in the nucleus tractus solitarii of rats
AlH-APRIL 1996-VOL. 9, NO.4, PART 2
POSTERS: Other Vasoactive Systems-Endothelin, NO, Vasopressin, etc
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ENDOGENOUS BETA-ENDORPHINS IN HYPERTENSION: CORRELATION WITH AMBULATORY BLOOD PRESSURE ~ Danerl A", Merlo B, Verga R, C.ttaneo R, GaUdio G, egaul MB', Gr.ndl AM', Baac.pe' YO, V.nco A. Dept. of Internal Med., Unlveralty of Pavia, II faculty .V.r...·, and Dept. of Pharmacol." IRCCS Pavia, Italy. Endogenoua oplolds are Involved In cardiovascular control m.chanlsms. However, only • few studies have Investigated beta..ndorphln plasma levels (BEPl) In hyp.rtenslve sUbJecta (pta) with controversl.1 resulta. Alms of this stUdy were:1) to show In a I.rge number of pta wh.ther BEPL were higher In hypertenslv. than In normotenslv. pltl and 2) to find possible correlations b.tween 24-hour (24·h) .mbulatory blood pr...ure (OP) and BEPL In 81 consecutlv. male pta (30-50 yrs), without treatment, blood samples for BEPL determination (RIA) were taken In the morning (9·11 am) .fter a 30'.,.st .nd before .mbulatory BP monitoring. Fourty..lght pte showed 24-h BP ~ 140 .nd/or 90 mmHg (hypertensives: 24-h systolic BP: 150±15, 24-h diastolic BP: 95±8 mmHg) whll. 33 pte were normotenslves (systolic BP: 123±8,diastollc BP: 77±8 mmHg). BEPL were hIgher In hypertensive than In normotensive pts (3.74~.31 vs 1.91±1.88 pg/ml p<.001). Positive correlations were found between BEPL .nd the following parametera: systolic 24-h .nd nocturnal BP (p<.05); diastolic 24-h, dIurnal .nd nocturnal BP (p<.005); diastolic lo.d (% of measures ~ 90mmHg/24-hl (p<.01); and diastolic BP m.asured before blood sampling (p<.05). A negative relationshIp was observed (star.dard between BEPL .nd coefficient of variation deviation/mean x 100) of 24-h diastolic BP (p<.005). This study shows an actlv.tlon of the .ndogenous oplold system In hypertension. Positive corr.latlons (the closest being with diastolic BP) were found between 24-h BP and baseline circulating endorphins while a negative relationship was observed between BEPL and coefficient of v.rlation of dIastoliC BP. These findings may account for a significant role of persistently high BP In the regulation of oplold tone.
RELATIONSHIP BETWEEN LEFT VENTRICULAR DIASTOLIC FUNCTION AND ATRIAL NATRIURETIC PEPTIDE IN HYPERTENSIVES. AM Grandi', G Gaudio, L Ceriani, A Bertolini, L Giovanella, P Zanzi, G Roncari, L Guasti, A Venco. Department of Internal Medicine-University of Pavia-Section of Varese-Italy High levels of atrial natriuretic peptide (ANP) in hypertension, found in many studies, have been ascribed to increased arterload, myocardial hypertrophy and / or ventricular diastolic impairment. Using digitized M-mode echocardiOl:rams, we have evaluated the relationship among a-ANP and morphologica. and functional characteristics of the left ventricle (LVI in %1 untreated hypertensive (H) men (mean age 4%±4 years) with normal renal function. Daytime (from 6 .m to 11 pm) BP was> t40 andlor 90 mmHg (systolic BP between t38 and 186 mmHg and diastolic BP between 89 snd 108 mmHg). For each subject we collected s blood sample for plasma aANP measurement (double antibody RIA kit, HANP-Eiken) and, immediately after, we recorded the LV echocardiogram. We evaluated: left atrial diameter (LAD), LV end-diastolic diameter (LVDD), LV mass indO's (LVMi), peak shortening (.dD/dt) and peak lengthenin!: rate (+dD/dt) of LV diameter, peak thinnin!: rate of LV posterior wall (-dW/dt), end-systolic wall stress (ESS). All the patients had normal LVDD « S6 10m) and LV systolic function (-dD/dt > t.9 sec-I); LV diastolic impairment (+dD/dt < 3.6 sec-I) was present In to H, 7 of whom had LV hypertrophy (LVMi > 130 J:/m2). ANP was not significantly different between H with normal LVMi (97±$3 pJ:/ml) .nd H with LV hypertrophy (11J±$7 pJ:/ml). ANP was significantly (p
Key Words: beta-endorphln, ambUlatory blood pressur., hypertension-essentlal·
KeyWords:
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H8
DIFFERENCES IN THE ROLE OF NITRIC OXIDE IN ACUTE AND CHRONIC AORTIC COARCTATION HYPERTENSION. E.J:!Qng and F Larios. CINVESTAV-IPN Mexico City, Mexico ' Pressor responses induced by inhibition of nitric oxide synthesis or by sympathetic electrical stimulation in acute and chronic aortic coarctation hypertension (60 minutes and 14-17 days, respectively) were investigated in pithed rats. Male wistar rats (300 to 350 g) were subjected to sham surgery or aortic coarctation by partial ligation of the abdominal aorta above the renal arteries Rats were anesthetized with ether and pithed through one orbit with a steel rod and immediatly ventilated. Mean blood pressure (MBP) was recorded from a carotid artery. Nitric oxide Inhibition was achieved by intravenous cumulative administration of N"·nitro-L-arginine methyl ester (L-NAME) at doses ranging from 0.1 to 31 mg/kg. MaXimal increases in MBP were obtained in sham operated rats with 10 mg/kg of L-NAME. However, pressor responses to L-NAME were much larger after acute coarctation, while a minimal change on MBP was observed In chronic coarctated rats In additional expenments, pressor responses to sympathetic electrical stimulation were elicited by means of an electrode placed into the spinal canal. Ten msec trains of square pulses of 0.5 msec duration and of supramaximal intensity at variable frequencies of stimulation were obtained in control, acute, and chronic hypertensive rats. Pressor responses were higher In chronic than 10 sham operated rats, while acute coarctated animals had attenuated responses. These results suggest that dunng the acute phase of hypertension there IS an increase in nitnc OXide syntheSiS, while the opposite occurs in the chronic established hypertension. This research was supported by grant 4379M from Conacyt Key Words: 't . 'd nl nc OXI e, L-NAME, aorta coarctation hypertension, sympathetiC stimUlation, pithed rat
CARDIOVASCULAR EFFECTS OF NITRIC OXIDE IN TIlE NUCLEUS TRACTUS SOLITARII OF RATS. CJ Tseng, WJ Ln, HC Lm and CS Tung. Dept. of Medical Education & Research, Veterans
Atrial natriuretic peptide, myocardial hypertrophy, lert ventricular diastolic function.
General Hospital-Kaohsiung. and Dept. of Pharmacology. National Defense Medical Center, TaIpei, Taiwan, Republtc of China. We preVIOusly reported that NO was involved in central cardiovascular regulation The purposes of the present study were to mvestlgate the poSSible involvement of NO in baroreflex regulation and other endogenous mechanlSlns that could contnbute to the final hemodynamiC response to NO m the nucleus tractus solttam (NTS) of rats In normotensive Sprague-Dawley rats, baroreflex response were eliCited by mcreasmg doses of phenylephrine before and after mtra· NTS admmistrallon of NO synthase mhlbltor N"-methyl-L-argmine (L-NMMA) or normal saltne. The reflex bradycardia eliCited by phenylephnne 'Yas Significantly inhibited by the pretreatment of LNMMA. Furthermore, the depressor and bradycardia eliCited by Largmme effects were blocked by pnor admlmstration of L-NMMA and by NMDA receptor antagonist MK-801 Similarly. pnor admmlstration of L-NMMA Significantly auenuated the depressor and bradycardlc elfect of glutamate or NMDA. The specifiCity of the NO·NMDA interaction 10 the NTS was demonstrated wtlh adrenergic and angIOtensin receptor antagomst that did not affect the L-argInme response in the NTS. These results demonstrated that endogenous NO IS Involved in barorenex regulation and a reciprocal allenuallon of NO synthase mhlbltor and NMDA receptor antagomst on NMDA and Larginme response was noted 10 the brainstem. and suggest that NO and NMDA may mteract in central cardiovascular regulation.
Key Words:
nitric oxide, nucleus tractus solitaril, cardIovascular. NMDA, baroreflex
51A
POSTERS: Other Vasoactive Systems-Endothelin, NO, Vasopressin, etc
H5
H6
ENDOGENOUS BETA-ENDORPHINS IN HYPERTENSION: CORRELATION WITH AMBULATORY BLOOD PRESSURE ~ Danerl A", Merlo B, Verga R, C.ttaneo R, GaUdio G, egaul MB', Gr.ndl AM', Baac.pe' YO, V.nco A. Dept. of Internal Med., Unlveralty of Pavia, II faculty .V.r...·, and Dept. of Pharmacol." IRCCS Pavia, Italy. Endogenoua oplolds are Involved In cardiovascular control m.chanlsms. However, only • few studies have Investigated beta..ndorphln plasma levels (BEPl) In hyp.rtenslve sUbJecta (pta) with controversl.1 resulta. Alms of this stUdy were:1) to show In a I.rge number of pta wh.ther BEPL were higher In hypertenslv. than In normotenslv. pltl and 2) to find possible correlations b.tween 24-hour (24·h) .mbulatory blood pr...ure (OP) and BEPL In 81 consecutlv. male pta (30-50 yrs), without treatment, blood samples for BEPL determination (RIA) were taken In the morning (9·11 am) .fter a 30'.,.st .nd before .mbulatory BP monitoring. Fourty..lght pte showed 24-h BP ~ 140 .nd/or 90 mmHg (hypertensives: 24-h systolic BP: 150±15, 24-h diastolic BP: 95±8 mmHg) whll. 33 pte were normotenslves (systolic BP: 123±8,diastollc BP: 77±8 mmHg). BEPL were hIgher In hypertensive than In normotensive pts (3.74~.31 vs 1.91±1.88 pg/ml p<.001). Positive correlations were found between BEPL .nd the following parametera: systolic 24-h .nd nocturnal BP (p<.05); diastolic 24-h, dIurnal .nd nocturnal BP (p<.005); diastolic lo.d (% of measures ~ 90mmHg/24-hl (p<.01); and diastolic BP m.asured before blood sampling (p<.05). A negative relationshIp was observed (star.dard between BEPL .nd coefficient of variation deviation/mean x 100) of 24-h diastolic BP (p<.005). This study shows an actlv.tlon of the .ndogenous oplold system In hypertension. Positive corr.latlons (the closest being with diastolic BP) were found between 24-h BP and baseline circulating endorphins while a negative relationship was observed between BEPL and coefficient of v.rlation of dIastoliC BP. These findings may account for a significant role of persistently high BP In the regulation of oplold tone.
RELATIONSHIP BETWEEN LEFT VENTRICULAR DIASTOLIC FUNCTION AND ATRIAL NATRIURETIC PEPTIDE IN HYPERTENSIVES. AM Grandi', G Gaudio, L Ceriani, A Bertolini, L Giovanella, P Zanzi, G Roncari, L Guasti, A Venco. Department of Internal Medicine-University of Pavia-Section of Varese-Italy High levels of atrial natriuretic peptide (ANP) in hypertension, found in many studies, have been ascribed to increased arterload, myocardial hypertrophy and / or ventricular diastolic impairment. Using digitized M-mode echocardiOl:rams, we have evaluated the relationship among a-ANP and morphologica. and functional characteristics of the left ventricle (LVI in %1 untreated hypertensive (H) men (mean age 4%±4 years) with normal renal function. Daytime (from 6 .m to 11 pm) BP was> t40 andlor 90 mmHg (systolic BP between t38 and 186 mmHg and diastolic BP between 89 snd 108 mmHg). For each subject we collected s blood sample for plasma aANP measurement (double antibody RIA kit, HANP-Eiken) and, immediately after, we recorded the LV echocardiogram. We evaluated: left atrial diameter (LAD), LV end-diastolic diameter (LVDD), LV mass indO's (LVMi), peak shortening (.dD/dt) and peak lengthenin!: rate (+dD/dt) of LV diameter, peak thinnin!: rate of LV posterior wall (-dW/dt), end-systolic wall stress (ESS). All the patients had normal LVDD « S6 10m) and LV systolic function (-dD/dt > t.9 sec-I); LV diastolic impairment (+dD/dt < 3.6 sec-I) was present In to H, 7 of whom had LV hypertrophy (LVMi > 130 J:/m2). ANP was not significantly different between H with normal LVMi (97±$3 pJ:/ml) .nd H with LV hypertrophy (11J±$7 pJ:/ml). ANP was significantly (p
Key Words: beta-endorphln, ambUlatory blood pressur., hypertension-essentlal·
KeyWords:
H7
H8
DIFFERENCES IN THE ROLE OF NITRIC OXIDE IN ACUTE AND CHRONIC AORTIC COARCTATION HYPERTENSION. E.J:!Qng and F Larios. CINVESTAV-IPN Mexico City, Mexico ' Pressor responses induced by inhibition of nitric oxide synthesis or by sympathetic electrical stimulation in acute and chronic aortic coarctation hypertension (60 minutes and 14-17 days, respectively) were investigated in pithed rats. Male wistar rats (300 to 350 g) were subjected to sham surgery or aortic coarctation by partial ligation of the abdominal aorta above the renal arteries Rats were anesthetized with ether and pithed through one orbit with a steel rod and immediatly ventilated. Mean blood pressure (MBP) was recorded from a carotid artery. Nitric oxide Inhibition was achieved by intravenous cumulative administration of N"·nitro-L-arginine methyl ester (L-NAME) at doses ranging from 0.1 to 31 mg/kg. MaXimal increases in MBP were obtained in sham operated rats with 10 mg/kg of L-NAME. However, pressor responses to L-NAME were much larger after acute coarctation, while a minimal change on MBP was observed In chronic coarctated rats In additional expenments, pressor responses to sympathetic electrical stimulation were elicited by means of an electrode placed into the spinal canal. Ten msec trains of square pulses of 0.5 msec duration and of supramaximal intensity at variable frequencies of stimulation were obtained in control, acute, and chronic hypertensive rats. Pressor responses were higher In chronic than 10 sham operated rats, while acute coarctated animals had attenuated responses. These results suggest that dunng the acute phase of hypertension there IS an increase in nitnc OXide syntheSiS, while the opposite occurs in the chronic established hypertension. This research was supported by grant 4379M from Conacyt Key Words: 't . 'd nl nc OXI e, L-NAME, aorta coarctation hypertension, sympathetiC stimUlation, pithed rat
CARDIOVASCULAR EFFECTS OF NITRIC OXIDE IN TIlE NUCLEUS TRACTUS SOLITARII OF RATS. CJ Tseng, WJ Ln, HC Lm and CS Tung. Dept. of Medical Education & Research, Veterans
Atrial natriuretic peptide, myocardial hypertrophy, lert ventricular diastolic function.
General Hospital-Kaohsiung. and Dept. of Pharmacology. National Defense Medical Center, TaIpei, Taiwan, Republtc of China. We preVIOusly reported that NO was involved in central cardiovascular regulation The purposes of the present study were to mvestlgate the poSSible involvement of NO in baroreflex regulation and other endogenous mechanlSlns that could contnbute to the final hemodynamiC response to NO m the nucleus tractus solttam (NTS) of rats In normotensive Sprague-Dawley rats, baroreflex response were eliCited by mcreasmg doses of phenylephrine before and after mtra· NTS admmistrallon of NO synthase mhlbltor N"-methyl-L-argmine (L-NMMA) or normal saltne. The reflex bradycardia eliCited by phenylephnne 'Yas Significantly inhibited by the pretreatment of LNMMA. Furthermore, the depressor and bradycardia eliCited by Largmme effects were blocked by pnor admlmstration of L-NMMA and by NMDA receptor antagonist MK-801 Similarly. pnor admmlstration of L-NMMA Significantly auenuated the depressor and bradycardlc elfect of glutamate or NMDA. The specifiCity of the NO·NMDA interaction 10 the NTS was demonstrated wtlh adrenergic and angIOtensin receptor antagomst that did not affect the L-argInme response in the NTS. These results demonstrated that endogenous NO IS Involved in barorenex regulation and a reciprocal allenuallon of NO synthase mhlbltor and NMDA receptor antagomst on NMDA and Larginme response was noted 10 the brainstem. and suggest that NO and NMDA may mteract in central cardiovascular regulation.
Key Words:
nitric oxide, nucleus tractus solitaril, cardIovascular. NMDA, baroreflex
51A