This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Burrell, L. M. Articles by Johnston, C. I. Search for Related Content PubMed PubMed Citation Articles by Burrell, L. M. Articles by Johnston, C. I.

Hypertension, Vol 23, 737-743, Copyright © 1994 by American Heart Association

ARTICLES

Blood pressure-lowering effect of an orally active vasopressin V1 receptor antagonist in mineralocorticoid hypertension in the rat

LM Burrell, PA Phillips, JM Stephenson, J Risvanis, KA Rolls and CI Johnston
University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia.

We studied the contribution of vasopressin to the maintenance of high blood pressure in deoxycorticosterone acetate (DOCA)-salt hypertension in the rat using the nonpeptide orally effective vasopressin V1 receptor antagonist OPC-21268. Binding kinetic studies demonstrated that oral OPC-21268 (30 mg/kg) acted as a competitive antagonist at the vasopressin V1 receptor in DOCA-salt and salt control rats. Basal mean intra-arterial blood pressure was 140 +/- 4 mm Hg (n = 12) in DOCA-salt rats compared with 111 +/- 2 mm Hg in salt control rats (n = 18). Acute oral OPC-21268 (30 mg/kg) significantly (P < .01) reduced mean intra- arterial pressure in DOCA-salt hypertension, with an average maximal decrease of 24 +/- 3 mm Hg occurring at 2.5 +/- 0.7 hours after dosing. Systolic blood pressure (tail-cuff) in DOCA-salt rats was 178 +/- 2 mm Hg. Chronic oral OPC-21268 (30 mg/kg) twice daily for 7 days significantly (P < .01) reduced systolic blood pressure in DOCA-salt hypertension, with an average maximal decrease of 27 +/- 5 mm Hg. The antihypertensive effect was reversed 5 days after treatment with OPC- 21268 was stopped. In water control rats basal systolic pressure (120 +/- 1 mm Hg, n = 20) was unchanged by chronic oral OPC-21268 (30 mg/kg twice daily for 7 days), and this was confirmed by direct measurement of mean intra-arterial pressure. After chronic oral OPC-21268 (30 mg/kg twice daily for 7 days) hepatic V1 receptor binding was significantly reduced for up to 10 hours (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				G. M. Pavan de Arruda Camargo, W. Abrao Saad, and L. A. de Arruda Camargo Vasopressin and angiotensin receptors of the medial septal area in the control of mean arterial pressure induced by vasopressin Journal of Renin-Angiotensin-Aldosterone System, September 1, 2008; 9(3): 133 - 138. [Abstract] [PDF]

				T.-a. Koshimizu, Y. Nasa, A. Tanoue, R. Oikawa, Y. Kawahara, Y. Kiyono, T. Adachi, T. Tanaka, T. Kuwaki, T. Mori, et al. From the Cover: V1a vasopressin receptors maintain normal blood pressure by regulating circulating blood volume and baroreflex sensitivity PNAS, May 16, 2006; 103(20): 7807 - 7812. [Abstract] [Full Text] [PDF]

				O. B. Vagnes, F. H. Hansen, J. J. Feng, B. M. Iversen, and W. J. Arendshorst Enhanced Ca2+ response to AVP in preglomerular vessels from rats with genetic hypertension during different hydration states Am J Physiol Renal Physiol, June 1, 2005; 288(6): F1249 - F1256. [Abstract] [Full Text] [PDF]

				C. Tahtaoui, M.-N. Balestre, P. Klotz, D. Rognan, C. Barberis, B. Mouillac, and M. Hibert Identification of the Binding Sites of the SR49059 Nonpeptide Antagonist into the V1a Vasopressin Receptor Using Sulfydryl-reactive Ligands and Cysteine Mutants as Chemical Sensors J. Biol. Chem., October 10, 2003; 278(41): 40010 - 40019. [Abstract] [Full Text] [PDF]

				L. Li, J. J. Galligan, G. D. Fink, and A. F. Chen Vasopressin Induces Vascular Superoxide Via Endothelin-1 in Mineralocorticoid Hypertension Hypertension, March 1, 2003; 41(3): 663 - 668. [Abstract] [Full Text] [PDF]

				H. E. De Wardener The Hypothalamus and Hypertension Physiol Rev, October 1, 2001; 81(4): 1599 - 1658. [Abstract] [Full Text] [PDF]

				M. Thibonnier, A. Kilani, M. Rahman, T. P. DiBlasi, K. Warner, M. C. Smith, A. F. Leenhardt, and R. Brouard Effects of the Nonpeptide V1 Vasopressin Receptor Antagonist SR49059 in Hypertensive Patients Hypertension, December 1, 1999; 34(6): 1293 - 1300. [Abstract] [Full Text] [PDF]

				H. D. Intengan, J. B. Park, and E. L. Schiffrin Blood Pressure and Small Arteries in DOCA-Salt-Treated Genetically AVP-Deficient Rats : Role of Endothelin Hypertension, October 1, 1999; 34(4): 907 - 913. [Abstract] [Full Text] [PDF]

				M. E Ullian The role of corticosteroids in the regulation of vascular tone Cardiovasc Res, January 1, 1999; 41(1): 55 - 64. [Full Text] [PDF]

				H. D. Intengan, G. He, and E. L. Schiffrin Effect of Vasopressin Antagonism on Structure and Mechanics of Small Arteries and Vascular Expression of Endothelin-1 in Deoxycorticosterone Acetate–Salt Hypertensive Rats Hypertension, October 1, 1998; 32(4): 770 - 777. [Abstract] [Full Text] [PDF]

				L. M. Burrell, P. A. Phillips, J. Risvanis, R. K. Chan, K. L. Aldred, and C. I. Johnston Long-term effects of nonpeptide vasopressin V2 antagonist OPC-31260 in heart failure in the rat Am J Physiol Heart Circ Physiol, July 1, 1998; 275(1): H176 - H182. [Abstract] [Full Text] [PDF]

				M. Nishimura, K. Ohtsuka, A. Nanbu, H. Takahashi, and M. Yoshimura Benzamil blockade of brain Na+ channels averts Na+-induced hypertension in rats Am J Physiol Regulatory Integrative Comp Physiol, March 1, 1998; 274(3): R635 - R644. [Abstract] [Full Text] [PDF]

				L. M. Burrell, P. A. Phillips, J. Risvanis, K. L. Aldred, A.-M. Hutchins, and C. I. Johnston Attenuation of Genetic Hypertension After Short-term Vasopressin V1A Receptor Antagonism Hypertension, November 1, 1995; 26(5): 828 - 834. [Abstract] [Full Text]