Endothelium-independent relaxation by 17-α-estradiol of pig coronary arteries

We have studied the effects of 17-α-estradiol, a non-estrogenic steroid, on pig coronary arteries contracted by K +, Ca 2+ or serotonin. Experiments were performed on helicoidal strips and rings of left circumflex coronary arteries from freshly slaughtered white pigs and on helicoidal strips of rat thoracic aorta. The strips and rings were suspended inside a water-jacketed muscle chamber in an oxygenated Krebs solution at 37°C. From the initial K +-evoked contraction, 17-α-estradiol caused a relaxation with an IC 50 (15 μM) which was in the range of the IC 50s obtained for nitroglycerin (1.3 μM) and nicorandil (50 μM). Contractions evoked by Ca 2+ were inhibited by 17-α-estradiol, but full blockade could not be achieved. Serotonin-evoked contractions were also blocked by 17-α-estradiol with an IC 50 of 2.1 μM; 17-β-estradiol also inhibited the serotonin-evoked contractions. In the presence of 100 μM of the nitric oxide synthase inhibitor N- nitro- L - arginine methyl ester, the relaxing properties of 17-α-estradiol in pig coronary arteries and rat thoracic aorta were unaffected, suggesting that endothelial NO release was unrelated to these effects. 17-α-Estradiol also relaxed denuded pig coronary artery strips, suggesting that other endothelial-derived relaxing factors were not involved in its vascular effects. The results are compatible with the idea that 17-α-estradiol causes relaxation of coronary vessels by acting directly on the cell membrane of smooth muscle cells; these effects seem to be unrelated to the genomic physiological effects of estrogens. These acute vasorelaxant effects can best be explained by blockade of voltage-dependent Ca 2+ channels and the ensuing restriction of extracellular Ca 2+ availability to the contractile machinery. This is in line with the recent hypothesis that estrogens behave as ‘endogenous Ca 2+ channel antagonists’.