Nitric oxide-induced cardioprotection in cultured rat ventricular myocytes

The aim of this study was to investigate the role of nitric oxide (NO) in a cellular model of early preconditioning (PC) in cultured neonatal rat vent ricular myocytes. Cardiomyocytes "preconditioned" with 90 min of stimulated ischemia (SI) followed by 30 min reoxygenation in normal culture condition s were protected against subsequent 6 h of SI. PC was blocked by NG-monomet hyl-L-arginine monoacetate but not by dexamethasone pretreatment. Inducible nitric oxide synthase (NOS) protein expression was not detected during PC ischemia. Pretreatment (90 min) with the NO donor S-nitroso-Nacetyl-L,L-pen icillamine (SNAP) mimicked PC, resulting in significant protection. SNAP-tr iggered protection was completely abolished by 1H-[1,2,4] oxadiazolo[4,3-a] quinoxalin-1-one (ODQ) but was unaffected by chelerythrine or the presence of glibenclamide and 5-hydroxydecanoate. With the use of RIA, SNAP treatme nt increased cGMP levels, which were blocked by ODQ. Hence, NO is implicate d as a trigger in this model of early PC via activation of a constitutive N OS isoform. After exposure to SNAP, the mechanism of cardioprotection is cG MP dependent but independent of protein kinase C or ATP-sensitive K+ channe ls. This differs from the proposed mechanism of NO-induced cardioprotection in late PC.