APStracts 3:0532H, 1996.

Estrogen treatment attenuates proliferation and agonist-induced calcium responses in cultured coronary artery smooth muscle cells. Bhalla, Ramesh C., Karen F. Toth, Robert A. Bhatty, Loren P. Thompson, and Ram V. Sharma. Departments of Anatomy, Obstetrics and Gynecology, and the Cardiovascular Center, The University of Iowa College of Medicine, Iowa City, IA 52242

APStracts 3:0532H, 1996.

Epidemiological evidence and estrogen replacement studies suggest that estrogen has a protective effect on the cardiovascular system against coronary artery disease. Vascular smooth muscle (VSM) cell replication has been shown to play a causative role in the pathogenesis of atherosclerosis. Therefore, in this study, we have investigated the effect of chronic treatment of cultured guinea pig coronary artery smooth muscle (VSM) cells with physiological concentrations of 17 [beta]-estradiol (E2) on thymidine incorporation, cell proliferation and bradykinin-stimulated cytosolic calcium concentration ([Ca2+]i). Bradykinin at physiological concentrations causes contraction of endothelium denuded guinea pig coronary artery rings in a concentration dependent manner. VSM cells were first treated with low doses of E2 (10 pg/ml) for 1-2 days followed by treatment for 4-6 days with 50 pg/ml E2, a concentration similar to that found in pregnancy. Using these protocols, we consistently observed the presence of E2 receptor mRNA in VSM cells by RNase protection assay. Fetal calf serum (FCS)-stimulated [3H] -thymidine incorporation was significantly reduced (P&LT;0.05) in E2-treated cells compared to untreated control cells. Similarly, E2 treatment significantly (P&LT;0.05) inhibited FCS-stimulated VSM cell proliferation compared to untreated control cells. We also tested the hypothesis that E2 treatment attenuates agonist-stimulated [Ca2+]i in VSM cells, since acute E2 treatment has been shown to produce relaxation of pre-contracted isolated coronary artery preparations. E2-treatment of VSM cells resulted in a significant (P&LT;0.05) decrease in bradykinin-stimulated [Ca2+]i compared with untreated cells. In conclusion, our data demonstrate that estrogen at physiological concentrations directly regulates coronary VSM cell function.

Received 20 November 1995; accepted in final form 17 May 1996.
APS Manuscript Number H1090-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996