Nitric oxide: a trigger for classic preconditioning?

To determine whether nitric oxide (NO) is involved in classic preconditioni ng (PC), the effect of NO donors as well as inhibition of the L-arginine-NO -cGMP pathway were evaluated on 1) the functional recovery during reperfusi on of ischemic rat hearts and 2) cyclic nucleotides during both the PC prot ocol and sustained ischemia. Tissue cyclic nucleotides were manipulated wit h NO donors [S-nitroso-N-penicillamine (SNAP), sodium nitroprusside (SNP), or L-arginine] and inhibitors of nitric oxide synthase (N-nitro-L-arginine methyl ester or N-nitro-L-arginine) or guanylyl cyclase (1H-[1,2,4] oxadiaz olol-[4,3-a] quinoxaline-1-one). Pharmacological elevation in tissue cGMP l evels by SNAP or SNP before sustained ischemia elicited functional improvem ent during reperfusion comparable to that by PC. Administration of inhibito rs before and during the PC protocol partially attenuated functional recove ry, whereas they had no effect when given after the ischemic PC protocol an d before sustained ischemia only, indicating a role for NO as a trigger but not as a mediator. Ischemic PC, SNAP, or SNP caused a significant increase in cGMP and a reduction in cAMP levels after 25 min of sustained ischemia that may contribute to the protection obtained. The results obtained sugges t a role for NO (and cGMP) as a trigger in classic PC.