Effects of nitric oxide on the contraction of skeletal muscle

A review of the literature suggests that the effects of nitric oxide (NO) o n skeletal muscles fibers can be classified in two groups. In the first, th e effects of NO are direct, due to nitrosation or metal nitrosylation of ta rget proteins: depression of isometric force, shortening velocity of loaded or unloaded contractions, glycolysis and mitochondrial respiration. The ef fect on calcium release channels varies, being inhibitory at low and stimul atory at high NO concentrations. The general consequence of the direct effe cts of NO is to 'brake' the contraction and its associated metabolism. In t he second group, the effects of NO are mediated by cGMP: increase of the sh ortening velocity of loaded or unloaded contractions, maximal mechanical po wer, initial rate of force development, frequency of tetanic fusion, glucos e uptake, glycolysis and mitochondrial respiration; decreases of half relax ation time of tetanus and twitch, twitch time-to-peak, force maintained dur ing unfused tetanus and of stimulus-associated calcium release. There is ne gligible effect on maximal force of isometric twitch and tetanus. The gener al consequence of cGMP-mediated effects of NO is to improve mechanical and metabolic muscle power, similar to a transformation of slow-twitch to fast- twitch muscle, an effect that we may summarize as a 'slow-to-fast' shift.