SUPERSENSITIVITY TO SEROTONIN-INDUCED AND HISTAMINE-INDUCED ARTERIAL CONTRACTION FOLLOWING OVARIECTOMY

The modulating role of estrogens and ovariectomy on coronary artery an d thoracic aortic rings was examined in female rabbits. Three treatmen t groups were studied: (1) control, (2) ovariectomy, and (3) ovariecto my + 17 beta-estradiol acetate (40 mu g/kg per day, i.m, for 7 days). Coronary artery reactivity was studied in the isolated retrogradely pe rfused heart. Aortic reactivity was studied using endothelium intact a nd 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-fo ld ina ease in sensitivity to 5-HT-induced contraction were observed i n the ovariectomy group compared to the control group for coronary art ery, 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 observ ed in the ovariectomy group compared to control group for coronary art ery, intact aortic, and denuded aortic preparations, respectively (P < 0.05 for each comparison). 17 beta-Estradiol administration reversed the supersensitivity to serotonin- and histamine-induced vascular cont raction observed following ovariectomy. No differences in ECS, or maxi mal 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 autac oid-induced nitrous oxide release following ovariectomy and (2) direct effects upon the vascular smooth muscle contractility, which are prob ably mediated by altered receptor sensitivity by ovariectomy and estro gen replacement therapy. The information obtained from this study prov ides additional information regarding possible beneficial actions of e strogen replacement therapy in post-menopausal women. (C) 1998 Elsevie r Science B.V. All rights reserved.