ACUTE EFFECTS OF 17-BETA-ESTRADIOL ON THE CORONARY MICROCIRCULATION -OBSERVATIONS IN SEDATED, CLOSED-CHEST DOMESTIC SWINE

Objectives To test the hypotheses: that acute administration of 17 bet a-estradiol dilates normal coronary microvessels in vivo; that coronar y microvascular responses to acute estrogen stimulation exhibit sexual dimorphism; and that nitric oxide has a role in mediating these effec ts. Methods Measurements of hemodynamics, coronary flow velocity (Dopp ler), myocardial blood flow (microspheres) and oxygen consumption were made in closed-chest swine: group 1 consisted of castrated juvenile m ales, groups 2 and 3 of estrogen pretreated, castrated juvenile males, and group 4 of sexually mature females. 17 beta-Estradiol (2, 20 or 2 00 ng/kg) was given by intracoronary injection and data obtained 20-30 min later; additional measurements were made 1 h after the 200 ng/kg dose. The effect of L-N-G-monomethylarginine (L-NMMA) on 17 beta-estra diol responses was also tested. Tissue and blood concentrations of 17 beta-estradiol, and concentrations of estrogen receptor in myocardium and coronary vessels were obtained. Results In estrogen-naive castrate d males, 17 beta-estradiol had no effect on coronary flow velocity or myocardial blood flow, but 1 h after the 200 ng/kg dose there was an i ncrease in diastolic coronary resistance compared with baseline (48 +/ - 20 versus 41 +/- 17 mmHg/mkHz; P< 0.05), Estrogen pretreated castrat ed males also showed no change in myocardial blood flow after 17 beta- estradiol, but coronary flow velocity decreased (P< 0.05) compared wit h baseline 1 h after the 200 ng/kg dose (from 1.69 +/- 0.61 to 1.41 +/ - 0.42 kHz) and diastolic coronary resistance increased significantly (P < 0.01) compared with control at this time (51 +/- 15 compared with 39 +/- 14 mmHg/mkHz). In sexually mature females, 17 beta-estradiol h ad no effect on myocardial blood flow but did cause a significant (P< 0.05) decrease in diastolic coronary vascular resistance compared with baseline (51 +/- 9 mmHg/mkHz) at both the 20 ng/kg and the 200 ng/kg doses (both 43 +/- 11 mmHg/mkHz), Coronary flow velocity also increase d (P< 0.06) compared with baseline (1.34 +/- 0.26 mmHg/mkHz) after the 200 ng/kg dose (1.69 +/- 0.61 mmHg/mkHz). L-NMMA had no effect on flo w responses to 17 beta-estradiol in any group. Classical estrogen rece ptors were not present in myocardium or coronary arteries from male or female swine. Conclusions These results demonstrate that 17 beta-estr adiol exerts a mild constrictor effect on the coronary microvessels of normal castrated, juvenile males whether estrogen-naive or estrogen-p retreated. In contrast, sexually mature normal females exhibit mild di latation of the coronary microcirculation in response to acute estroge n stimulation. Nitric oxide does not appear to have a role in mediatin g the dilator response in females, and classical estrogen receptors ar e not involved. A direct membrane effect of the hormone (perhaps via a lteration in potassium conductance) seems likely, and demonstrates sex ual dimorphism. (C) Rapid Science Publishers.