ENDOTHELIUM-INDEPENDENT RELAXATION OF HUMAN CORONARY-ARTERIES BY 17-BETA-ESTRADIOL IN-VITRO

Objective: There is accumulating evidence that oestrogen replacement therapy protects against the development of coronary atherosclerosis and myocardial infarction in postmenopausal women. The mechanism of this protective effect is uncertain. The aim of this study was to measure the effects of 17beta-oestradiol on human epicardial coronary artery tone. Methods: Coronary artery rings were obtained from explanted hearts during cardiac transplantation. The rings were suspended in organ baths for isometric tension measurements. The rings were precontracted with prostaglandin F2alpha, and were then exposed to either 17beta-oestradiol (0.3 nM-3 muM) or solvent control (0.2% ethanol v/v). In some rings, cyclic adenosine 3',5'-monophosphate and cyclic guanosine 3',5'-monophosphate content were measured by radioimmunoassay. Results: 17beta-Oestradiol induced a significant relaxation [maximum effect: 84(SD 18)%]. The onset of the relaxant effect occurred within 5 min, and was maximal within 40 min. The relaxation in response to 3 muM 17beta-oestradiol was of similar magnitude in rings with and without intact endothelium. The maximum relaxation induced by 3 muM 17beta-oestradiol was greater in arteries from hearts obtained from women than in those obtained from men [-100.0(3.0)% v -77.5(17.6)%, respectively]. The exposure of rings to 3 muM 17beta-oestradiol for 30 min resulted in a significant increase in both cyclic AMP and cyclic GMP content, by 88% and 182%, respectively. Conclusions: 17beta-Oestradiol produced an endothelium independent relaxation of precontracted human coronary arteries in vitro, and this effect was associated with an increase in both cyclic AMP and the cyclic GMP content. This direct relaxant effect of oestrogens on coronary arteries may contribute to the beneficial effects of oestrogen replacement therapy in postmenopausal women.