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, A. Takeshita

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Arginine vasopressin (AVP) plays an 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. The effects of intravenous OPC-21268 at 30 mg/kg was similar to those of the Manning compound (a specific V1-receptor antagonist) at 10 mg/kg. OPC-21268 did not affect the phenylephrine-induced increases in blood pressure and reflex decreases in heart rate and RSNA. These results may suggest that OPC-21268 is a potent V1-receptor antagonist and that oral OPC-21268 is partially effective to antagonize the V1-receptor-mediated decreases in heart rate and RSNA.

Original languageEnglish
Pages (from-to)R1089-R1094
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume264
Issue number6 33-6
Publication statusPublished - Jan 1 1993

Fingerprint

OPC 21268
Vasopressin Receptors
Arginine Vasopressin
Heart Rate
Kidney

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

Cite this

Effects of a novel orally effective V1-receptor antagonist, OPC-21268, on AVP-induced sympathoinhibition. / Masaki, H.; Imaizumi, T.; Harada, S.; Momohara, M.; Hirooka, Y.; Takeshita, A.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 264, No. 6 33-6, 01.01.1993, p. R1089-R1094.

Research output: Contribution to journalArticle

Masaki, H, Imaizumi, T, Harada, S, Momohara, M, Hirooka, Y & Takeshita, A 1993, 'Effects of a novel orally effective V1-receptor antagonist, OPC-21268, on AVP-induced sympathoinhibition', American Journal of Physiology - Regulatory Integrative and Comparative Physiology, vol. 264, no. 6 33-6, pp. R1089-R1094.
Masaki, H. ; Imaizumi, T. ; Harada, S. ; Momohara, M. ; Hirooka, Y. ; Takeshita, A. / Effects of a novel orally effective V1-receptor antagonist, OPC-21268, on AVP-induced sympathoinhibition. In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. 1993 ; Vol. 264, No. 6 33-6. pp. R1089-R1094.
@article{2d7842af8e1340c1b56378a01f030f76,
title = "Effects of a novel orally effective V1-receptor antagonist, OPC-21268, on AVP-induced sympathoinhibition",
abstract = "Arginine vasopressin (AVP) plays an 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. The effects of intravenous OPC-21268 at 30 mg/kg was similar to those of the Manning compound (a specific V1-receptor antagonist) at 10 mg/kg. OPC-21268 did not affect the phenylephrine-induced increases in blood pressure and reflex decreases in heart rate and RSNA. These results may suggest that OPC-21268 is a potent V1-receptor antagonist and that oral OPC-21268 is partially effective to antagonize the V1-receptor-mediated decreases in heart rate and RSNA.",
author = "H. Masaki and T. Imaizumi and S. Harada and M. Momohara and Y. Hirooka and A. Takeshita",
year = "1993",
month = "1",
day = "1",
language = "English",
volume = "264",
pages = "R1089--R1094",
journal = "American Journal of Physiology",
issn = "0363-6119",
publisher = "American Physiological Society",
number = "6 33-6",

}

TY - JOUR

T1 - Effects of a novel orally effective V1-receptor antagonist, OPC-21268, on AVP-induced sympathoinhibition

AU - Masaki, H.

AU - Imaizumi, T.

AU - Harada, S.

AU - Momohara, M.

AU - Hirooka, Y.

AU - Takeshita, A.

PY - 1993/1/1

Y1 - 1993/1/1

N2 - Arginine vasopressin (AVP) plays an 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. The effects of intravenous OPC-21268 at 30 mg/kg was similar to those of the Manning compound (a specific V1-receptor antagonist) at 10 mg/kg. OPC-21268 did not affect the phenylephrine-induced increases in blood pressure and reflex decreases in heart rate and RSNA. These results may suggest that OPC-21268 is a potent V1-receptor antagonist and that oral OPC-21268 is partially effective to antagonize the V1-receptor-mediated decreases in heart rate and RSNA.

AB - Arginine vasopressin (AVP) plays an 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. The effects of intravenous OPC-21268 at 30 mg/kg was similar to those of the Manning compound (a specific V1-receptor antagonist) at 10 mg/kg. OPC-21268 did not affect the phenylephrine-induced increases in blood pressure and reflex decreases in heart rate and RSNA. These results may suggest that OPC-21268 is a potent V1-receptor antagonist and that oral OPC-21268 is partially effective to antagonize the V1-receptor-mediated decreases in heart rate and RSNA.

UR - http://www.scopus.com/inward/record.url?scp=0027158247&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027158247&partnerID=8YFLogxK

M3 - Article

C2 - 8391757

AN - SCOPUS:0027158247

VL - 264

SP - R1089-R1094

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6119

IS - 6 33-6

ER -