Delayed anti-arrhythmic effect of nitroglycerin in anesthetized rats: Involvement of CGRP, PKC and mK_ATP channels☆

Abstract 

Delayed anti-infarct and anti-stunning effects of nitroglycerin (NTG) have well been established in some animal models. The main goals of this study in anesthetized rats were to determine whether NTG has a delayed anti-arrhythmic effect and if so, whether calcitonin gene-related peptide (CGRP), protein kinase C (PKC) and mitochondrial K_ATP channels (mK_ATP) are involved in triggering this response. For this purpose, on day 0, male Wistar rats received NTG (120 μg/kg, iv) with or without pre-administration of PKC inhibitor chelerythrine (CHE), capsaicin (CAP) to deplete CGRP from sensory nerves or mK_ATP channel blocker 5-hydroxydecaonic acid (5HD). On day 1, their hearts were subjected to 30 min ischemia and 120 min reperfusion. In rats pretreated with NTG, the incidence of ventricular tachycardia and ventricular fibrillation and the mortality rate significantly reduced (from 100%, 61% and 18.1% in the control group to 45.4%, 10% and 0% in the NTG group, respectively). Infarct size also reduced from 58±4.7% in the control group to 31±3.7% in the NTG group. These effects were abolished by CHE, CAP and 5HD, which none of them alone had any effect on infarct size or the incidence of myocardial arrhythmias. These results show that a low dose of NTG has a delayed anti-arrhythmic effect and this effect may share a common mechanism with anti-infarct effects of this drug, involving CGRP release and PKC and mK_ATP activation.

Keywords: Nitroglycerin, CGRP, PKC, mK_ATP, Arrhythmia