Estrogen augments cyclopiazonic acid-mediated, endothelium-dependent vasodilation

Document Type

Article

Publication Title

European Journal of Pharmacology

ISSN

0014-2999

Volume

327

Issue

2-3

DOI

10.1016/S0014-2999(97)89653-7

First Page

143

Last Page

149

Publication Date

5-30-1997

Abstract

The modulatory effects of chronic estrogen treatment on the responses to cyclopiazonic acid, an endoplasmic reticulum Ca -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 to 3 X 10 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 < 0.05, one-way analysis of variance (ANOVA)). These relaxation responses of cyclopiazonic acid were converted to contractions by pre-treatment with an inhibitor of nitric oxide (NO) synthase, Nω-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 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 entry into the endothelial cells. 2+ -7 -5 -5 2+

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