Effects of a novel orally effective V1-receptor antagonist, OPC-21268, on AVP-induced sympathoinhibition.
Arginine vasopressin (AVP) plays as important role in control of circulation and may be involved in pathophysiology of cardiovascular diseases. Recently a novel oral V1-receptor antagonist, OPC-21268, has been produced for possible human therapeutic use (Y. Yamamure et al. Science Wash. DC 252: 572-574, 1991). OPC-21268 is a nonpeptide antagonist and inhibits AVP-induced vasoconstriction in rats and humans. In this study, we examined the influence of OPC-21268 on the sympathoinhibitory and bradycardic effects of AVP in conscious rabbits. Before OPC-21268, AVP at doses of 1, 3, 10, and 30 mU/kg decreased renal sympathetic nerve activity (RSNA) by 24 +/- 5, 40 +/- 5, 65 +/- 6 and 86 +/- 5%, respectively, and decreased heart rate from 243 +/- 10 beats/min at control to 232 +/- 11, 221 +/- 10, 197 +/- 9, and 166 +/- 6 beats/min, respectively (n = 12). Oral OPC-21268 at 30 mg/kg (n = 12) and 90 mg/kg (n = 5) did not alter the baseline values of arterial pressure, heart rate, and RSNA. After oral OPC-21268 the decreases in RSNA and heart rate evoked with AVP at graded doses were partially but significantly attenuated (P < 0.01). The attenuation of the AVP-induced decreases in RSNA and heart rate was similar between the two doses of OPC-21268. In another group of rabbits (n = 6), intravenous OPC-21268 at 30 mg/kg almost completely abolished AVP-induced decreases in heart rate and RSNA.(ABSTRACT TRUNCATED AT 250 WORDS)
Research Institute of Angiocardiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
H
H
Masaki
T
T
Imaizumi
S
S
Harada
M
M
Momohara
Y
Y
Hirooka
A
A
Takeshita
D000284:Administration, Oral; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D007668:Kidney / Q000294:innervation; D008297:Male; D009433:Neural Inhibition; D010656:Phenylephrine / Q000494:pharmacology; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D015363:Quinolones / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014667:Vasopressins / Q000037:antagonists & inhibitors
D065092:Antidiuretic Hormone Receptor Antagonists; D010880:Piperidines; D015363:Quinolones; D014667:Vasopressins; D001127:Arginine Vasopressin; C068644:OPC 21268; D010656:Phenylephrine; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-