Supersensitivity to serotonin- and histamine-induced arterial contraction following ovariectomy.

The modulating role of estrogens and ovariectomy on coronary artery and thoracic aortic rings was examined in female rabbits. Three treatment groups were studied: (1) control, (2) ovariectomy, and (3) ovariectomy + 17beta-estradiol acetate (40 microg/kg per day, i.m. for 7 days). Coronary artery reactivity was studied in the isolated retrogradely perfused heart. Aortic reactivity was studied using endothelium intact and denuded aortic rings. Concentration-response curves were performed to serotonin (5-HT) and histamine. A 21-fold, a 4.7-fold, and a 5.2-fold increase in sensitivity to 5-HT-induced contraction were observed in the ovariectomy group compared to the control group for coronary artery, intact aortic, and denuded aortic preparations, respectively (P < 0.05 for each comparison). Similarly, 34-fold, 4.9-fold, and 5.0-fold increases in sensitivity to histamine-induced contraction were observed in the ovariectomy group compared to control group for coronary artery, intact aortic, and denuded aortic preparations, respectively (P < 0.05 for each comparison). 17beta-Estradiol administration reversed the supersensitivity to serotonin- and histamine-induced vascular contraction observed following ovariectomy. No differences in EC50 or maximal contraction were noted between control and ovariectomy + estrogen groups. Baseline nitric oxide release and maximal 5-HT- and histamine-induced nitric oxide release from the perfused heart were decreased (P < 0.05) in ovariectomy rabbits compared to control and ovariectomy + estrogen treatment groups. The data demonstrate that (1) reduced autacoid-induced nitrous oxide release following ovariectomy and (2) direct effects upon the vascular smooth muscle contractility, which are probably mediated by altered receptor sensitivity by ovariectomy and estrogen replacement therapy. The information obtained from this study provides additional information regarding possible beneficial actions of estrogen replacement therapy in post-menopausal women.