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Effects of direct-acting vasodilators on cardiac sympathetic nerve activity and heart rate in rats
J Mol
Cell
Cardiol21
(Supplement
II) (1989)
P.loTHE
EFFECT OF SK&F 64139 (A PNMT INHIBITOR) ON BLOOD PRESSURE, HEART RATE, SYMPATHETIC NERVE ACTIVITY AND MYOCAROIAL CATECHOLAMINE CONTENTS IN RAT. H. Sato, N. Hamaue, M. Nishikiori, M. Minami, H. Togashi? M. Yoshiokar H. Saito? Dept., of Pharmacol., Higashi-Nippon-Gakuen Univ., Ishikari-Tobetsu, Hokkaido, Facul. of Pharmac. Sci., First Dept. of Pharmacol.? Hokkaido Univ. Sch. of Med., Sapporo, Japan. , catalyzes norepinephrine (NE) to PNMT, Phenylethanolamine N-methyltransferase SK&F 64139 (SKF) is a epinephrine (Ep) in final steps of catecholamine synthesis. potent, reversible inhibitor of PNMT. The present study was undertaken to elucidate the effects of SKF on blood pressure (BP), heart rate (HR) and catecholamine (CA) contents of heart tissue in rats. Rats were anesthetized with chloralose and urethane BP and HR were recorded directly via the femoral artery with a pressure transducer. Myocardial CA contents were measured using HPLC-ECD. Myocardial protein contents were assayed by Lowry's method. Maximal BP reduction was shown after 15 minutes SKF administration (10 mg/kg, i.v.) and significant hypotensive phase continued for up to 60 minutes. The change in HR paralleled with that in BP. 15 minutes after SKF, HR was reduced by 90 beats per minutes. SKF-treated rats showed tendency to decrease in myocardial NE contents of right ventricle compared with those of vehicle treated rats. Forthermore, to elucidate the mechanism of negative chronotropic effect by SKF, sympathetic nerve activity was recorded. Sympathetic nerve activity paralleled with those in BP and HR. These results suggests that negative chronotropic effect induced by SKF might be mainly drived from central nervous system.
P.11
KETANSERIN ON CARDIAC SYMPATHETIC NERVE ACTIVITY AND EFFECTS OF 5-HT2 BLOCKER, HEART RATE IN RATS. H. Togashi, M. Matsumoto, M. Yoshioka, M. Minami*, H. Saito. First Department of Pharmacology Hokkaido University School Of Medicine, Sapporo, Japan. *Department of Pharmacology Higashi-Nippon-Gakuen University Faculty Pharmaceutical Sciences, Ishikari-Tobetsu, Japan. Present study was undertaken to elucidate the effects of 5-HT2 blocker, ketanserin on cardiac sympathetic nerve activity and heart rate in buffer nerveAn attempt was also made to clarify the effect of ketanserin on intact rats. postganglionic renal nerve activity and preganglionic adrenal Iler"e activity. Ketanserin produced bradycardia and a decrease in mean arterial pressure. Inferior cardiac nerve activity and renal nerve activity were also reduced by ketanserin. After i.v. ketanserin administration, baroreceptor afferent nerve activity did not increase, but actually decreased. Moreover. i-v. and i.c.v. administration of ketanserin caused a decrease in preganglionic adrenal nerve activity accompanied with hypotension and bradycardia. These findings suggest that ketanserin has a central sympathoinhibitory action and this central action may play a role in ketanserin-induced bradycardia.
p.12
EFFECTS OF DIRECT-ACTING VASODILATORS ON CARDIAC SYMPATHETIC NERVE ACTIVITY AND HEART RATE IN RATS. M. Yoshioka, H. Togashi, M. Minami*, Hideya Saito. First Department of Pharmacology Hokkaido University School of Medicine, Sapporo, Japan. *Department of Pharmacology Higashi-Nippon-Gakuen University Faculty Pharmaceutical Sciences, Ishikari-Tobetsu, Japan. It has been realized that a phthalazin derivative, hydralazine, produced a vasodilating action accompanied with reflex tachycardia. However, another phthalazin derivative, budralazine is also a direct-acting vasodilating agent but this drug does not produce marked tachycardia. Present study was designed to clarify this different heart rate changes induced by hydralazine and budralazine. The effects of these two drugs on inferior cardiac nerve activity (ICNA) and heart rate were studied in anesthetized rats. Hydralazine (lmg/kg,i.v.) produced a significant increase in ICNA accompanied with tachycardia and hypotension. On the other hand, budralazine (O.Smg/kg,i.v.) produced a decrease in ICNA and bradycardia in parallel with a significant decrease in blood pressure. These results suggest that increased ICNA induced by hydralazine may be mainly responsible for the reflex tachycardia. Although budralazine produced a significant reduction of blood pressure, central sympathoinhibitory action of budralazine may prevent from baroreceptor mediated reflex tachycardia.
8.189
Cell
Cardiol21
(Supplement
II) (1989)
P.loTHE
EFFECT OF SK&F 64139 (A PNMT INHIBITOR) ON BLOOD PRESSURE, HEART RATE, SYMPATHETIC NERVE ACTIVITY AND MYOCAROIAL CATECHOLAMINE CONTENTS IN RAT. H. Sato, N. Hamaue, M. Nishikiori, M. Minami, H. Togashi? M. Yoshiokar H. Saito? Dept., of Pharmacol., Higashi-Nippon-Gakuen Univ., Ishikari-Tobetsu, Hokkaido, Facul. of Pharmac. Sci., First Dept. of Pharmacol.? Hokkaido Univ. Sch. of Med., Sapporo, Japan. , catalyzes norepinephrine (NE) to PNMT, Phenylethanolamine N-methyltransferase SK&F 64139 (SKF) is a epinephrine (Ep) in final steps of catecholamine synthesis. potent, reversible inhibitor of PNMT. The present study was undertaken to elucidate the effects of SKF on blood pressure (BP), heart rate (HR) and catecholamine (CA) contents of heart tissue in rats. Rats were anesthetized with chloralose and urethane BP and HR were recorded directly via the femoral artery with a pressure transducer. Myocardial CA contents were measured using HPLC-ECD. Myocardial protein contents were assayed by Lowry's method. Maximal BP reduction was shown after 15 minutes SKF administration (10 mg/kg, i.v.) and significant hypotensive phase continued for up to 60 minutes. The change in HR paralleled with that in BP. 15 minutes after SKF, HR was reduced by 90 beats per minutes. SKF-treated rats showed tendency to decrease in myocardial NE contents of right ventricle compared with those of vehicle treated rats. Forthermore, to elucidate the mechanism of negative chronotropic effect by SKF, sympathetic nerve activity was recorded. Sympathetic nerve activity paralleled with those in BP and HR. These results suggests that negative chronotropic effect induced by SKF might be mainly drived from central nervous system.
P.11
KETANSERIN ON CARDIAC SYMPATHETIC NERVE ACTIVITY AND EFFECTS OF 5-HT2 BLOCKER, HEART RATE IN RATS. H. Togashi, M. Matsumoto, M. Yoshioka, M. Minami*, H. Saito. First Department of Pharmacology Hokkaido University School Of Medicine, Sapporo, Japan. *Department of Pharmacology Higashi-Nippon-Gakuen University Faculty Pharmaceutical Sciences, Ishikari-Tobetsu, Japan. Present study was undertaken to elucidate the effects of 5-HT2 blocker, ketanserin on cardiac sympathetic nerve activity and heart rate in buffer nerveAn attempt was also made to clarify the effect of ketanserin on intact rats. postganglionic renal nerve activity and preganglionic adrenal Iler"e activity. Ketanserin produced bradycardia and a decrease in mean arterial pressure. Inferior cardiac nerve activity and renal nerve activity were also reduced by ketanserin. After i.v. ketanserin administration, baroreceptor afferent nerve activity did not increase, but actually decreased. Moreover. i-v. and i.c.v. administration of ketanserin caused a decrease in preganglionic adrenal nerve activity accompanied with hypotension and bradycardia. These findings suggest that ketanserin has a central sympathoinhibitory action and this central action may play a role in ketanserin-induced bradycardia.
p.12
EFFECTS OF DIRECT-ACTING VASODILATORS ON CARDIAC SYMPATHETIC NERVE ACTIVITY AND HEART RATE IN RATS. M. Yoshioka, H. Togashi, M. Minami*, Hideya Saito. First Department of Pharmacology Hokkaido University School of Medicine, Sapporo, Japan. *Department of Pharmacology Higashi-Nippon-Gakuen University Faculty Pharmaceutical Sciences, Ishikari-Tobetsu, Japan. It has been realized that a phthalazin derivative, hydralazine, produced a vasodilating action accompanied with reflex tachycardia. However, another phthalazin derivative, budralazine is also a direct-acting vasodilating agent but this drug does not produce marked tachycardia. Present study was designed to clarify this different heart rate changes induced by hydralazine and budralazine. The effects of these two drugs on inferior cardiac nerve activity (ICNA) and heart rate were studied in anesthetized rats. Hydralazine (lmg/kg,i.v.) produced a significant increase in ICNA accompanied with tachycardia and hypotension. On the other hand, budralazine (O.Smg/kg,i.v.) produced a decrease in ICNA and bradycardia in parallel with a significant decrease in blood pressure. These results suggest that increased ICNA induced by hydralazine may be mainly responsible for the reflex tachycardia. Although budralazine produced a significant reduction of blood pressure, central sympathoinhibitory action of budralazine may prevent from baroreceptor mediated reflex tachycardia.
8.189