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Our studies in the mRen2. Lewis female rat, an angiotensin II-and estrogen-dependent model of hypertension, revealed that chronic activation of estrogen receptor GPR30 markedly reduces blood pressure in ovariectomized females. The present studies measured acute vasodilation to the selective GPR30 agonist G-1 and 17-β-estradiol (10− 9-10− 5.5 M) in isolated aortic rings and mesenteric arteries from intact mRen2. Lewis females. Maximal relaxation was greater in mesenteric vessels versus the aorta for both G-1 (47%±8% vs 80%±5% of phenylephrine preconstriction, P< 0.001) and estradiol (42%±7% vs 83%±4% of phenylephrine preconstriction, P< 0.001). The GPR30 antagonist G15 attenuated the response to both estradiol and G-1. Removal of the endothelium or pretreatment with Nitro-L-arginine methyl ester (L-NAME) partially attenuated vasorelaxation. Responses were not altered in mesenteric …