HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 289/3/H1258    most recent 00352.2005v1 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 Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Honoré, J.-C. Articles by D’Orleans-Juste, P. Search for Related Content PubMed PubMed Citation Articles by Honoré, J.-C. Articles by D’Orleans-Juste, P.

Concomitant antagonism of endothelial and vascular smooth muscle cell ET_B receptors for endothelin induces hypertension in the hamster

Departments of ¹Pharmacology and ²Anatomy and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec, Canada

Submitted 11 April 2005 ; accepted in final form 29 April 2005

In the vascular system, endothelin (ET) type B (ET_B) receptors for ET-1 are located on endothelial and on venous and arterial smooth muscle cells. In the present study, we investigated the hemodynamic effects of chronic ET_B receptor blockade at low and high doses in the Syrian Golden hamster. After 16 days of gavage with A-192621 (0.5 or 30 mg·kg^–1·day^–1), a selective ET_B receptor antagonist, hamsters were anesthetized with a mixture of ketamine and xylazine (87 and 13 mg/kg im, respectively), and basal mean arterial blood pressure (MAP) and pressor responses to exogenous ET-1 were evaluated. The lower dose of A-192621 (0.5 mg·kg^–1·day^–1) did not modify basal MAP, whereas the higher dose (30 mg·kg^–1·day^–1) increased MAP and plasma ET levels. Radio-telemetry recordings confirmed the increase in MAP induced by the higher dose of A-192621 in conscious hamsters. On the other hand, although the lower dose of A-192621 was devoid of intrinsic pressor effects, it markedly reduced the transient hypotensive phase induced by intravenously injected IRL-1620, a selective ET_B receptor agonist. Finally, A-192621 (0.5 mg·kg^–1·day^–1) alone or A-192621 (30 mg·kg^–1·day^–1) + atrasentan (6 mg·kg^–1·day^–1), a selective ET_A receptor antagonist, potentiated the pressor response to exogenous ET-1. Our results suggest that, in the hamster, ET_B receptors on vascular smooth muscle cells are importantly involved in the clearance of endogenous ET-1, whereas the same receptor type on the endothelium is solely involved in the vasodilatory responses to the pressor peptide. Blockade of endothelial and vascular smooth muscle cell ET_B receptors triggers a marked potentiation of ET_A-dependent increases in systemic resistance.

clearance; telemetry

This article has been cited by other articles:

				K. Sachidanandam, M. M. Elgebaly, A. K. Harris, J. R. Hutchinson, E. M. Mezzetti, V. Portik-Dobos, and A. Ergul Effect of chronic and selective endothelin receptor antagonism on microvascular function in Type 2 diabetes Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2743 - H2749. [Abstract] [Full Text] [PDF]

				A. E. Linder, J. Diaz, W. Ni, T. Szasz, R. Burnett, and S. W. Watts Vascular reactivity, 5-HT uptake, and blood pressure in the serotonin transporter knockout rat Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1745 - H1752. [Abstract] [Full Text] [PDF]

				Z. Abassi, B. Bishara, T. Karram, S. Khatib, J. Winaver, and A. Hoffman Adverse effects of pneumoperitoneum on renal function: involvement of the endothelin and nitric oxide systems Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2008; 294(3): R842 - R850. [Abstract] [Full Text] [PDF]

				G. Fink, M. Li, Y. Lau, J. Osborn, and S. Watts Chronic Activation of Endothelin B Receptors: New Model of Experimental Hypertension Hypertension, September 1, 2007; 50(3): 512 - 518. [Abstract] [Full Text] [PDF]