Effects of 17 beta-estradiol on coronary microvascular responses to endothelin-1

The objective of this study was to examine the effects of 17 beta-estradiol on responses of coronary microvessels to endothelin-1 (ET-1). With the use of isolated pressurized coronary microvessels from the left ventricle of male or female dogs, constrictions to ET-1 were similar in vessels from male and female dogs. 17 beta-Estradiol (1 mu M) attenuated constriction to ET-1 of small arteries from both male (percent constriction at 10 mu M control: 39 +/- 9%, estradiol: 3 +/- 2%; P < 0.05) and female (percent constriction at 10 mu M control: 39 +/- 8%, estradiol: 6 +/- 3%; P < 0.05) dogs similarly. In contrast, testosterone (1 mu M) had no effect on constriction to ET-1. Constrictions to ET-1 were completely abolished by BQ-123 (1 mu M), a selective ET(A)-receptor antagonist, and enhanced by BQ-788 (1 mu M), a selective ET(B)-receptor antagonist. Constrictions to ET-1 alone were not altered by indomethacin (Indo, 10 mu M) or N-G-nitro-L-arginine (L-NNA, 100 mu M). 17 beta-Estradiol produced dose-dependent relaxation of coronary microvessels preconstricted with ET-1 that was similar to the response to testosterone and progesterone. Indo or L-NNA alone had no effect on relaxation to 17 beta-estradiol. However, the combination of Indo and L-NNA attenuated relaxation to 17 beta-estradiol (percent dilation at 1 mu M control: 64 +/- 13%; Indo plus L-NNA: 21 +/- 6%; P < 0.05) but did not affect relaxation to testosterone. Thus 17 beta-estradiol attenuated constrictions of coronary microvessels to ET-1 more than did similar concentrations of testosterone. The ability of 17 beta-estradiol to modulate responses to endothelin may involve release of vasodilator prostaglandins and/or nitric oxide by 17 beta-estradiol.