AJP - Regulatory, Integrative and Comparative Physiology, Vol 264, Issue 6 1089-R1094, Copyright © 1993 by American Physiological Society
Effects of a novel orally effective V1-receptor antagonist, OPC-21268, on AVP-induced sympathoinhibition
H. Masaki, T. Imaizumi, S. Harada, M. Momohara, Y. Hirooka and A. Takeshita
Research Institute of Angiocardiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
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)
