In:
Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 99, No. 5 ( 2006-09)
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
0009-7330
,
1524-4571
DOI:
10.1161/01.RES.0000241051.83067.62
Sprache:
Englisch
Verlag:
Ovid Technologies (Wolters Kluwer Health)
Publikationsdatum:
2006
ZDB Id:
1467838-X
