Alterations in aortic vascular reactivity to angiotensin 1-7 in 17-beta-estradiol-treated female SD rats.
Estrogen's suggested cardio-protective effects have come into question following the results of recent clinical trials. Two major components of the renin-angiotensin system (RAS) that are modulated by estrogen are angiotensin converting enzyme, and the angiotensin II type 1 receptor. Further research has revealed several new components of the RAS, including angiotensin converting enzyme 2, its peptide product angiotensin 1-7 (Ang 1-7), and that peptide's receptor, Mas. These components appear to oppose the classical effects of the RAS, and may act to buffer the RAS in vivo. Recent work has shown that during pregnancy, when estradiol levels are elevated, renal and urinary Ang 1-7 are greatly increased. This study examined the effects of estradiol on the efficacy of Ang 1-7 in the rat aorta. Female Sprague-Dawley rats were ovariectomized and a subgroup was chronically treated with subcutaneous pellets of estradiol for 3 weeks. Thoracic aortas were harvested for assessment of in vitro vascular reactivity to Ang 1-7. The results demonstrated that increased estradiol exposure attenuated the relaxation response to Ang 1-7 in a dose-dependent manner. These findings are in contrast to recent work showing potentiated responses to Ang 1-7 in mesenteric arteries from estrogen-manipulated rats, and may suggest a regional specificity in estradiol-mediated changes in the RAS.
Grobe
Justin L
JL
Department of Pharmacodynamics, University of Florida College of Pharmacy, JHMHSC, PO Box 100487, Gainesville, FL 32610, USA.
Katovich
Michael J
MJ
D000803:Angiotensin I / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000378:metabolism* / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D000959:Antihypertensive Agents; D010446:Peptide Fragments; D004958:Estradiol; D000803:Angiotensin I; C118790:angiotensin I (1-7)