Acute effect of 17 beta-estradiol on rabbit coronary artery contractile responses to endothelin-1.
We assessed the acute effect of 17 beta-estradiol on coronary artery constrictor responses to endothelin-1. 17 beta-Estradiol significantly shifted endothelin-1, calcium, or BAY K 8644 concentration-dependent contraction curves to the right in endothelium-denuded coronary arteries isolated from nonpregnant female rabbits. The -log 50% effective dose (ED50) of calcium in high KCl medium (100 mM) was 3.8 +/- 0.11 in control and 3.2 +/- 0.1 and 2.8 +/- 0.12 after incubation with 17 beta-estradiol (1 and 10 microM, respectively). The -log ED50 of BAY K 8644 (KCl 15 mM) was 7.8 +/- 0.1 in control and 7.4 +/- 0.08 and 7.2 +/- 0.05 in the presence of 17 beta-estradiol (1 and 10 microM, respectively). The -log ED50 of endothelin-1 was 9.2 +/- 0.08 in control and 8.8 +/- 0.1, 8.4 +/- 0.07, and 8.1 +/- 0.12 after incubation with 17 beta-estradiol (3, 10, and 30 microM, respectively). Similar results were obtained from coronary arteries of male rabbits. These increases of -log ED50 values were significant (P less than 0.05 or 0.01). 17 beta-Estradiol and verapamil induced dose-dependent relaxation in both endothelium-intact or -denuded coronary arteries submaximally precontracted by endothelin-1. NG-monomethyl-L-arginine had no effect on relaxation induced by 17 beta-estradiol, whereas it eliminated relaxation induced by acetylcholine in rings with an intact endothelium. These data suggest that 17 beta-estradiol attenuates the rabbit coronary artery contraction induced by endothelin-1 via an endothelium-independent mechanism, possibly by affecting calcium influx.
Jiang
C
C
Department of Cardiac Medicine, University of London, United Kingdom.
Sarrel
P M
PM
Poole-Wilson
P A
PA
Collins
P
P
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D016232:Endothelins / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D016232:Endothelins; D004958:Estradiol; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D014700:Verapamil; D002118:Calcium