Ischemic tolerance in skeletal muscle: role of nitric oxide.

We tested the hypothesis that ischemic preconditioning (PC) of skeletal muscle provided tolerance to a subsequent ischemic event 24 h later, and that such protection was due to nitric oxide (NO). Male Wistar rats, anesthetized with halothane, were randomly assigned to groups: ischemic (no PC;n = 11), PC (n = 11), PC +N-nitro-l-arginine methyl ester (l-NAME; 100 μmol/l; n = 5), PC +N-nitro-d-arginine methyl ester (100 μmol/l; n= 4), PC + aminoguanidine (AMG; 100 μmol/l;n = 4), ischemic +l-NAME (n= 4), or ischemic + AMG (n = 4). PC consisted of 5× 10 min of ischemia and reperfusion, and, 24 h later, 2 h of ischemia were induced by a tourniquet applied to the limb. With the use of intravital microscopy, the number of perfused capillaries (N pc) in the extensor digitorum longus (EDL) muscle was measured over a 90-min reperfusion period. The ratio of ethidium bromide- to bisbenzimide-labeled nuclei was used to estimate tissue injury. PC preserved N pc(23.6 ± 2.5) following 2 h of ischemia compared with sham mu...