Sex hormone modulation of serotonin-induced coronary vasodilation in isolated heart

The present study was designed to evaluate the differences in the coronary vasodilator actions of serotonin (5-HT) in isolated heart obtained from nai ve or castrated male and female rats that were treated with either estrogen or testosterone, Hearts from 12 groups of rats were used: male and female naive animals, castrated, castrated and treated with 17 beta -estradiol (0. 5 mug kg(-1) day(-1)) for 7 or 30 days, and castrated and treated with test osterone (0.5 mg kg(-1) day(-1)) for 7 or 3 days. After treatment, the vasc ular reactivity of the coronary bed was evaluated. Baseline coronary perfus ion pre-sure (CPP) was determined and dose-response curves to 5-HT were gen erated. Baseline CPP differed between male (70 +/- 6 mmHg, N = 10) and fema le (115 +/- 6mmHg, N = 12) naive rats. Maximal 5-HT-induced coronary vasodi lation was higher (P < 0.05) in naive female than in naive male rats. In bo th sexes. 5-HT produced endothelium-dependent coronary vasodilation. After castration, there was no significant difference in baseline CPP between hea rts obtained from male and female rats (75 +/- 7 mmHg, N = 8, and 83 +/- 5 mmHg, N = 8, respectively). Castration reduced the 5-HT-induced maximal vas odilation in female and male rats (P < 0.05). Estrogen treatment of castrat ed female rats restored (P < 0.05) the vascular reactivity. In castrated ma le rats, 30 days of estrogen treatment increased (P < 0.05) the responsiven ess to 5-HT. The endothelium-dependent coronary vasodilator actions of 5-HT are greater in female rats and are modulated by estrogen. A knowledge of t he mechanism of action of estrogen on coronary arteries could aid in the de velopment of new therapeutic strategies and potentially decrease the incide nce of cardiovascular disease in both sexes.