Estrogen augments cyclopiazonic acid-mediated, endothelium-dependent vasodilation

Abstract The modulatory effects of chronic estrogen treatment on the responses to cyclopiazonic acid, an endoplasmic reticulum Ca 2+ -ATPase inhibitor, were studied in rings of aorta and the isolated perfused kidney of the rat. Rings of aorta were obtained from the following groups of age-matched rats (i) male, (ii) female, and two groups of rats implanted with a subcutaneous pellet (iii) ovariectomized, placebo-treated, (iv) ovariectomized, 17β-estradiol-treated (0.5 mg/pellet/21 days). In phenylephrine (2 μM) pre-contracted rings with intact endothelium, cyclopiazonic acid (10 −7 to 3×10 −5 M) produced endothelium-dependent relaxations in a concentration-dependent manner. The cyclopiazonic acid dilation as a percentage loss of phenylephrine tone was greater in aortic rings from female (72.9±2.4%) and estrogen-treated rats (65.5±4.8%) compared to those from male (51.5±3.4%) or ovariectomized rats (40.8±3.9%) ( P N ω -nitro- l -arginine methyl ester ( l -NAME, 200 μM; 30 min). There were no differences in cyclopiazonic acid-induced contractions of aortas excised from either estrogen-treated or untreated-ovariectomized rats. In perfused kidneys, cyclopiazonic acid (10 −5 M) caused a larger decrease in perfusion pressure in kidneys from female rats (110±0.4 mmHg) than it did in kidneys from male rats (80±0.6 mmHg). These results demonstrate that cyclopiazonic acid causes a greater endothelium-dependent dilation in estrogen-treated ovariectomized and control female rats, possibly due to unmasking of estrogen-enhanced Ca 2+ entry into the endothelial cells.