Increased cyclooxygenase-2 expression and prostaglandin-mediated dilation in coronary arterioles of patients with diabetes mellitus.
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 microm 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 micromol/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.
Szerafin
Tamás
T
Institute of Cardiology, University of Debrecen, Hungary.
Erdei
Nóra
N
Fülöp
Tibor
T
Pasztor
Eniko T
ET
Edes
István
I
Koller
Akos
A
Bagi
Zsolt
Z
D000368:Aged; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D001920:Bradykinin / Q000494:pharmacology; D016022:Case-Control Studies; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011453:Prostaglandins / Q000378:metabolism*; D014664:Vasodilation; D014666:Vasomotor System / Q000503:physiopathology
D011453:Prostaglandins; D051546:Cyclooxygenase 2; D001920:Bradykinin