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 microM) attenuated constriction to ET-1 of small arteries from both male (percent constriction at 10 microM control: 39 +/- 9%, estradiol: 3 +/- 2%; P < 0.05) and female (percent constriction at 10 microM control: 39 +/- 8%, estradiol: 6 +/- 3%; P < 0.05) dogs similarly. In contrast, testosterone (1 microM) had no effect on constriction to ET-1. Constrictions to ET-1 were completely abolished by BQ-123 (1 microM), a selective ETA-receptor antagonist, and enhanced by BQ-788 (1 microM), a selective ETB-receptor antagonist. Constrictions to ET-1 alone were not altered by indomethacin (Indo, 10 microM) or NG-nitro-L-arginine (L-NNA, 100 microM). 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 Taxation to 17 beta-estradiol (percent dilation at 1 microM 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.
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Department of Internal Medicine, College of Medicine, University of Iowa, Iowa City 52242, USA.
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D000818:Animals; D001808:Blood Vessels / Q000378:metabolism; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D019332:Endothelin-1 / Q000494:pharmacology*; D011464:Epoprostenol / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology; D017466:Receptors, Endothelin / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D019332:Endothelin-1; D012739:Gonadal Steroid Hormones; D017466:Receptors, Endothelin; D012503:Saponins; D009569:Nitric Oxide; D004958:Estradiol; D011464:Epoprostenol