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.