In the present study we tested the hypothesis that angiotensin II (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 NO synthase by 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. Acetylcholine, a NO-dependent relaxing hormone produced greater relaxation in the aortic rings of obese than lean rats, while sodium nitroprusside, an NO donor elicited similar relaxations in both rat strains. The expression of the AT₁ receptor protein and mRNA in the endothelium intact aorta was significantly greater in obese than lean rats, whereas the endothelium denuded rings express modest but not significantly greater levels of AT₁ receptors in obese than lean rats. The eNOS 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.