Published online before print August 17, 2006, doi: 10.1161/01.RES.0000241051.83067.62
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© 2006 American Heart Association, Inc.
UltraRapid Communication |
Increased Cyclooxygenase-2 Expression and Prostaglandin-Mediated Dilation in Coronary Arterioles of Patients With Diabetes Mellitus
From the Institute of Cardiology (T.S., N.E., T.F., E.T.P., I.E., Z.B.), University of Debrecen, Hungary; the Department of Physiology (A.K.), New York Medical College, Valhalla; and the Department of Pathophysiology, Semmelweis University, Budapest, Hungary.
Correspondence to Zsolt Bagi MD, PhD, Division of Clinical Physiology, Institute of Cardiology, University of Debrecen, Medical and Health Science Center, Faculty of Medicine, H-4032 Debrecen, Moricz Zs. krt 22. Hungary. E-mail bagizs{at}jaguar.unideb.hu
Based on findings of experimental models of diabetes mellitus (DM) showing increased expression of vascular cyclooxygenase-2 (COX-2), we hypothesized that in patients with DM changes in COX-2–dependent prostaglandin synthesis affect vasomotor responses of coronary arterioles. Arterioles were dissected from the right atrial appendages obtained at the time of cardiac surgery of patient with DM(+) or without documented diabetes DM(–). Isolated arterioles (89±15 µm in diameter) were cannulated and pressurized (at 80 mm Hg), and changes in diameter were measured with video microscopy. After spontaneous tone developed [DM(–): 32±7%; DM(+): 37±5%; P=NS], arteriolar responses to bradykinin were investigated. Dilations to bradykinin (0.1 nmol/L to 1 µmol/L) were significantly (P<0.05) greater in DM(+) than DM(–) patients (10 nmol/L: 77±10% versus 38±14%). In both groups, dilations were similar to the NO-donor, sodium nitroprusside. In arterioles of DM(+), but not those of DM(–), patients’ bradykinin-induced dilations were reduced by the nonselective COX inhibitor indomethacin or by the selective COX-2 inhibitor NS-398 (DM(+) at 10 nmol/L: to 20±4% and 29±7%, respectively). Correspondingly, a marked COX-2 immunostaining was detected in coronary arterioles of DM(+), but not in those of DM(–) patients. We conclude that in coronary arterioles of diabetic patients bradykinin induces enhanced COX-2–derived prostaglandin-mediated dilation. These findings are the first to show that in humans diabetes mellitus increases COX-2 expression and dilator prostaglandin synthesis in coronary arterioles, which may serve to increase dilator capacity and maintain adequate perfusion of cardiac tissues.
Key Words: diabetes mellitus • human coronary arteriole • endothelium • bradykinin • cyclooxygenase 2 • prostacyclin
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