Published online before print August 17, 2006, doi: 10.1161/01.RES.0000241051.83067.62
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Submitted on July 6, 2006
Revised on July 24, 2006
Accepted on August 3, 2006
Increased Cyclooxygenase-2 Expression and Prostaglandin-Mediated Dilation in Coronary Arterioles of Patients With Diabetes Mellitus
Tamás Szerafin ;
From the Institute of Cardiology (T.S., N.E., T.F., E.T.P., I.E., Z.B.), University of Debrecen, Hungary; and the Department of Physiology (A.K.), New York Medical College, Valhalla.
* To whom correspondence should be addressed. 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 (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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