Enhanced AT^sub 1^ receptor-mediated vasocontractile response to ANG II in endothelium-denuded aorta of obese Zucker rats

• Published in: American journal of physiology. Heart and circulatory physiology 2007-04, Vol.292 (4), p.H1722
• Main Authors: Siddiqui, Athar H, Hussain, Tahir
• Format: Article
• Language: English
• Subjects: ACE inhibitors; Anatomy & physiology; Coronary vessels; Obesity; Protein synthesis; Rodents
• ISSN: 0363-6135; 1522-1539

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...-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... 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 pD... values. Endothelin-1 and KC1 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 (AT...) 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 AT... 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 AT... receptor-mediated NO production appears to counteract the increased ANG II-induced vasoconstriction, suggesting that arterial AT... receptor may not be a contributing factor to hypertension in this model of obesity. (ProQuest-CSA LLC: ... denotes formulae/symbols omitted.)