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: 292/4/H1722    most recent 00612.2006v1 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 ISI 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 ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Siddiqui, A. H. Articles by Hussain, T. Search for Related Content PubMed PubMed Citation Articles by Siddiqui, A. H. Articles by Hussain, T.

Enhanced AT₁ receptor-mediated vasocontractile response to ANG II in endothelium-denuded aorta of obese Zucker rats

Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, Texas

Submitted 9 June 2006 ; accepted in final form 22 November 2006

In the present study, we tested the hypothesis that ANG II causes a greater vasoconstriction in obese Zucker rats, a model of type 2 diabetes, with mild hypertension. Measurement of isometric tension in isolated aortic rings with intact endothelium revealed a modest but not significantly greater ANG II-induced contraction in obese than lean rats. Removal of endothelium or inhibition of nitric oxide (NO) synthase by N^G-nitro-L-arginine methyl ester (L-NAME) enhanced 1) ANG II-induced contraction in both lean and obese rats, being significantly greater in obese rats (E_max g/g tissue, denuded: lean 572 ± 40 vs. obese 664 ± 16; L-NAME: lean 535 ± 14 vs. obese 818 ± 23) and 2) ANG II sensitivity in obese compared with lean rats, as revealed by the pD₂ values. Endothelin-1 and KCl elicited similar contractions in the aortic rings of lean and obese rats. ACh, a NO-dependent relaxing hormone, produced greater relaxation in the aortic rings of obese than lean rats, whereas sodium nitroprusside, an NO donor, elicited similar relaxations in both rat strains. The expression of the ANG type 1 (AT₁) receptor protein and mRNA in the endothelium-intact aorta was significantly greater in obese than lean rats, whereas the endothelium-denuded rings expressed modest but not significantly greater levels of AT₁ receptors in obese than lean rats. The endothelial NO synthase protein and mRNA expression levels were higher in the aorta of obese than lean animals. We conclude that, although ANG II produces greater vasoconstriction in obese rat aortic rings, enhanced endothelial AT₁ receptor-mediated NO production appears to counteract the increased ANG II-induced vasoconstriction, suggesting that arterial AT₁ receptor may not be a contributing factor to hypertension in this model of obesity.

angiotensin II; endothelium; thoracic aorta; N^G-nitro-L-arginine methyl ester; angiotensin II type 1 receptor messenger ribonucleic acid

This article has been cited by other articles:

				J. H. Lee, S. Xia, and L. Ragolia Upregulation of AT2 receptor and iNOS impairs angiotensin II-induced contraction without endothelium influence in young normotensive diabetic rats Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2008; 295(1): R144 - R154. [Abstract] [Full Text] [PDF]