Unmasking a role for nitric oxide in acetylcholine‐induced vasodilation in diseased human coronary arterioles.

Abstract

BackgroundAcetylcholine (ACH) dose‐dependently constricts human coronary atrial arterioles (HCA) but dilates ventricular arterioles in patients with coronary disease. Whether NO mechanisms participate in Ach‐induced dilation in atrial arterioles remains unclear. Since CAD and its risk factors generate ROS that can quench NO, we hypothesized that acetylcholine‐induced dilation can be restored in HCA by restoring redox balance and supporting exogenous NO synthesis.MethodsArterioles (~150 μm) from patients with coronary artery disease were prepared for videomicroscopy. HCA's were pre‐incubated with indomethacin (10‐5), sepiapterin (10‐4), L‐Arginine (10‐3), and Peg‐SOD (300units/ml) for 30 minutes. After preconstruction with endothelin‐1, vasomotor responses to exogenous ACH (10‐9 to 10‐4 M) were evaluated in control or in the presence and absence of N‐nitro‐L‐arginine methyl ester (L‐name; 10‐4)).ResultsACH dilated pretreated compared to control intact arterioles [%max dilation (MD): 80±8% vs. ‐36.4±7%]. Treatment with L‐name abolished dilation (MD:‐0.5±9%).ConclusionsReducing endogenous oxidative stress and providing NOS substrate converts an , ACH‐induced constriction to an NO ‐dependent vasodilation in HCA. There may be a greater sensitivity to ROS in endothelium of atrial vs. ventricular arterioles.