OP4 - Nitroglycerin-induced cardioprotection is endothelial nitric oxide synthase- dependent

Abstract

Purpose We sought to evaluate the contribution of the endogenous NO pathway to the cardioprotective action of nitroglycerin (NTG). Methods and Results Anesthetized rabbits were subjected to 30-min myocardial ischemia (isc) and 3-h reperfusion (rep) and randomized into: Control group (no further intervention); PostC group (application of 8 cycles 30-sec isc/rep) and NTG treated group (2 μg/kg-1/min-1 IV bolus) for 65 min starting 10 min prior to rep. In additional groups, pharmacological inhibitors of NOS, nNOS, iNOS, PI3K, adenosine receptors and PKG were administrated with or without NTG. The infarcted (I) to risk (R) ratio was estimated. In a second experimental series tissue samples were collected from Control, PostC, NTG and NTG L-NAME groups in the 10th min of rep for determination of eNOS and Akt and of myocardial ROS-RNS by DHE staining, and nitrotyrosine and MDA levels evaluation. Inhibition of NOS or PI3K along with NTG eliminated the effect of NTG on %I/R (37.9±2.0%, and 38.3±2.6% respectively vs 23.0±3.2%, p