Acute hyperglycemia impairs NO‐mediated endothelial function of coronary arterioles by reducing L‐arginine availability independent of superoxide

Abstract

Diabetes is associated with oxidative stress leading to impaired coronary flow regulation. However, the impact of acute elevation of glucose on coronary arteriolar function remains unclear. Herein, we examined the direct influence of high glucose on endothelium‐dependent nitric oxide (NO)‐mediated dilation of coronary arterioles and the role of superoxide in the high glucose‐mediated effect. Porcine coronary arterioles were isolated and pressurized without flow for in vitro study. In the presence of normal intraluminal physiological level of glucose (5 mM), coronary arterioles dilated dose‐dependently to endothelium‐dependent NO‐mediated agonist serotonin. In another group of vessels, the vasodilation to serotonin, but not to sodium nitroprusside, was reduced by an acute (90 min) elevation of intraluminal glucose in a concentration‐dependent manner (25 and 50 mM). Subsequent exposure of vessels to excess of NO precursor L‐arginine (3 mM), but not to superoxide dismutase mimetic TEMPOL, restored the normal dilation to serotonin. Our data show that acute exposure to high glucose can specifically impair endothelium‐dependent NO‐mediated dilation of coronary arterioles. It appears that reduction in L‐arginine availability, rather than increase in superoxide production, contributes to the endothelial dysfunction induced by an acute elevation of glucose. Support: HL‐71761 to LK.