Chronic estrogen alters contractile responsiveness to angiotensin II and norepinephrine in female rat aorta.
Sex hormones have been postulated to play an important role in the modulation of vascular responsiveness to endogenous vasoactive substances. This study was designed to establish the effects of chronic treatment with estrogen in vivo on subsequent contractile responsiveness of aortic rings to angiotensin II or norepinephrine in vitro. Concentration-response curves for angiotensin II were compared in aortic rings with or without endothelium isolated from ovariectomized rats (275-299 g) pretreated with 17 beta-estradiol (approximately 1 mg/kg per day) or placebo for 14 days and from normal prepubertal female rats (125-149 g) pretreated with 17 beta-estradiol (approximately 5 mg/kg per day) or placebo for 14 days. Whether or not endothelium was present, angiotensin II-induced contraction was significantly depressed in rings from 17 beta-estradiol-treated ovariectomized or prepubertal rats when compared to controls, and the pattern of the effects of 17 beta-estradiol-treatment on the concentration-response curves for angiotensin II was similar in the two models. In contrast to angiotensin II-induced contraction, norepinephrine-induced contraction was significantly enhanced in aortic rings with or without endothelium from ovariectomized rats pretreated with 17 beta-estradiol (approximately 1 mg/kg per day, 14 days) and from normal prepubertal female rats pretreated with 17 beta-estradiol (approximately 5 mg/kg per day, 14 days) when compared to controls. The results demonstrate that chronic treatment with 17 beta-estradiol selectively reduced and enhanced contractile responsiveness of aortic rings to angiotensin II and norepinephrine, respectively. Further, the results indicate that the normal prepubertal female rat is an efficient model to investigate modulation by estrogen of aortic responsiveness to vasoactive agents in vitro.
Cheng
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DY
Department of Pharmacology, Marshall University School of Medicine, Huntington, WV 25755-9310.
Gruetter
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CA
D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects
D004967:Estrogens; D000804:Angiotensin II; D004958:Estradiol; D009638:Norepinephrine