Inhibitory effect of glucocorticoid on coronary artery endothelial function.
Acute and chronic stresses are implicated in cardiovascular diseases including coronary artery disease. The present study was designed to examine the direct effects of the stress hormone cortisol on nitric oxide (NO) release and endothelial NO synthase (eNOS) expression in cultured bovine coronary artery endothelial cells (BCAEC). Nitrate, nitrite, and NO (NO(x)) were measured by the chemiluminescence method. At 24 h after treatment, cortisol (1 nM-10 microM) produced a dose-dependent decrease in NO(x) release, which was attenuated in the presence of the 11beta-hydroxysteroid dehydrogenase inhibitor carbenoxolone (3 microM). In accordance, eNOS protein levels were significantly decreased by cortisol in a dose-dependent manner. Cortisol pretreatment significantly increased the rate of eNOS protein degradation in the presence of cycloheximide. In addition, cortisol pretreatment decreased ATP-induced intracellular Ca(2+) elevation and NO(x) release in BCAEC. The presence of glucocorticoid receptors in BCAEC was demonstrated by Western blot. The results suggest that cortisol, through activation of glucocorticoid receptors, suppresses NO(x) release in BCAEC by downregulating eNOS proteins and inhibiting intracellular Ca(2+) mobilization. Decreased NO(x) is likely to result in an increase in contraction of coronary arteries, leading to a decrease in coronary blood flow.
Rogers
Kestrel M
KM
Department of Chemistry, California State University, San Bernardino, CA 92407, USA.
Bonar
Christi A
CA
Estrella
Jaymie L
JL
Yang
Shumei
S
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects*; D003600:Cytosol / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D006854:Hydrocortisone / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III
D000893:Anti-Inflammatory Agents; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D002118:Calcium; D006854:Hydrocortisone