Influence of endothelin-1 on clonidine-induced cardiovascular effects in anesthetized rabbits.
This study was designed to investigate the effect of endothelin-1 (ET-1) on clonidine-induced cardiovascular effects in urethane-anesthetized rabbits and to clarify the mechanism of its action. Clonidine (5, 10, and 20 micrograms/kg) given into a femoral vein (i.v.) produced a marked dose-dependent fall in arterial blood pressure and heart rate, but intracerebroventricular (i.c.v.) clonidine (2, 4, and 8 micrograms/kg) induced a slight depressor effect and bradycardia. Intravenous clonidine-induced hypotension was significantly enhanced by pretreatment with ET-1 or sarafotoxin, but the bradycardia was not affected. Intracerebroventricular clonidine-induced depressor responses were greatly inhibited by sarafotoxin pretreatment but not by ET-1. Both i.v. and i.c.v. ET-1 and sarafotoxin elicited marked hypotensive responses, with a slight decrease in heart rate. The depressor action evoked by i.v. ET-1 and sarafotoxin was significantly inhibited by nitroprusside but not by phentolamine or sodium acetylsalicylate. Furthermore, the weak bradycardia induced by ET-1 or sarafotoxin was not influenced by pretreatment with phentolamine, nitroprusside, or sodium acetylsalicylate. Taken together, these experimental data suggest that ET-1 potentiates clonidine-induced hypotensive responses in the urethane-anesthetized rabbit through facilitation of nitric oxide release, which appears to be associated with endothelin receptors.
Lim
D Y
DY
Department of Pharmacology, College of Medicine, Chosun University, Kwangju, Korea.
Heo
K
K
Choi
C H
CH
Lee
E W
EW
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000768:Anesthesia, General; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology*; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D011817:Rabbits
D000316:Adrenergic alpha-Agonists; D019332:Endothelin-1; D003000:Clonidine