To test the hypotheses: that acute administration of 17β-estradiol dilates normal coronary microvessels in vivo; that coronary microvascular responses to acute estrogen stimulation exhibit sexual dimorphism; and that nitric oxide has a role in mediating these effects.
Measurements of hemodynamics, coronary flow velocity (Doppler), myocardial blood flow (microspheres) and oxygen consumption were made in closed-chest swine: group 1 consisted of castrated juvenile males, groups 2 and 3 of estrogen pretreated, castrated juvenile males, and group 4 of sexually mature females. 17β-Estradiol (2, 20 or 200 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-Ng-monomethylarginine (L-NMMA) on 17β-estradiol responses was also tested. Tissue and blood concentrations of 17β-estradiol, and concentrations of estrogen receptor in myocardium and coronary vessels were obtained.
In estrogen-naive castrated males, 17β-estradiol had no effect on coronary flow velocity or myocardial blood flow, but 1 h after the 200 ng/kg dose there was an increase in diastolic coronary resistance compared with baseline (48 ± 20 versus 41 ± 17 mmHg/mkHz; P<0.05). Estrogen pretreated castrated males also showed no change in myocardial blood flow after 17β-estradiol, but coronary flow velocity decreased (P<0.05) compared with 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, 17β-estradiol had 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 increased (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 flow responses to 17β-estradiol in any group. Classical estrogen receptors were not present in myocardium or coronary arteries from male or female swine.
These results demonstrate that 17β-estradiol exerts a mild constrictor effect on the coronary microvessels of normal castrated, juvenile males whether estrogen-naive or estrogen-pretreated. In contrast, sexually mature normal females exhibit mild dilatation of the coronary microcirculation in response to acute estrogen stimulation. Nitric oxide does not appear to have a role in mediating the dilator response in females, and classical estrogen receptors are not involved. A direct membrane effect of the hormone (perhaps via alteration in potassium conductance) seems likely, and demonstrates sexual dimorphism.
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