Estrogen pretreatment directly potentiates endothelium-dependent vasorelaxation of porcine coronary arteries.
We tested whether vasorelaxation of coronary arteries is altered after overnight (18-22 h) exposure to physiological levels of 17 beta-estradiol. Ring segments of left circumflex coronary artery from six female and six castrated male pigs were incubated in vials of sterile Dulbecco's modified Eagle's medium with 1 nM 17 beta-estradiol, 1 nM 17 beta-estradiol + 10 nM tamoxifen, 1 nM 17 alpha-estradiol, or estrogen vehicle (ethanol) under normoxic conditions in an O2-CO2 incubator at 37 degrees C for 18-22 h. Coronary rings, with and without endothelium, were then suspended in vessel baths for measurement of isometric force. Vasorelaxation responses to the calcium ionophore A-23187, ADP, and nitroglycerin were examined in the rings after prostaglandin synthesis blockade and precontraction with U-46619. Sensitivity to A-23187 (-log M concentration required for 50% of maximal relaxation) was significantly enhanced in coronary rings with endothelium from females and castrated males when rings were incubated with 17 beta-estradiol but not when they were incubated with 17 alpha-estradiol or 17 beta-estradiol+tamoxifen. Acute (2h) exposure of coronary arteries to 1 nM 17 beta-estradiol did not alter responses to A-23187. 17 beta-Estradiol (1 nM) was not itself directly vasoactive in coronary arteries with or without prior incubation with the steroid. Vasorelaxation of rings with and without endothelium to ADP and nitroglycerin was not significantly different among the treatment groups. Relaxation to A-23187, but not ADP, was abolished by removal of the endothelium or exposure to 100 microM NO2-L-arginine.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Physiology and Biophysics, School of Medicine, Indiana University, Fort Wayne 46805.
D R
DR
Bell
H J
HJ
Rensberger
D R
DR
Koritnik
A
A
Koshy
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D019335:Nitroarginine; D005996:Nitroglycerin / Q000494:pharmacology; D009919:Orchiectomy; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D012016:Reference Values; D012727:Sex Characteristics; D013552:Swine; D013629:Tamoxifen / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D013629:Tamoxifen; D019335:Nitroarginine; D000001:Calcimycin; D004958:Estradiol; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D001120:Arginine; D005996:Nitroglycerin