SKELETAL-MUSCLE CONTRACTIONS STIMULATE CGMP FORMATION AND ATTENUATE VASCULAR SMOOTH-MUSCLE MYOSIN PHOSPHORYLATION VIA NITRIC-OXIDE

Nitric oxide generated by neuronal nitric oxide synthase in contractin g skeletal muscle fibers may regulate vascular relaxation via a cGMP-m ediated pathway. Neuronal nitric oxide synthase content is greatly red uced in skeletal muscles from mdx mice. cGMP formation increased in co ntracting extensor digitorum longus muscles in vitro from C57 control, but not mdx mice. The increase in cGMP content was abolished with NG- nitro-L-arginine. Sodium nitroprusside treatment increased cGMP levels in muscles from both C57 and mdx mice. Skeletal muscle contractions a lso inhibited phenylephrine-induced phosphorylation of smooth muscle m yosin regulatory light chain. Arteriolar dilation was attenuated in co ntracting muscles from mdx but not C57 mice. NO generated in contracti ng skeletal muscle may contribute to vasodilation in response to exerc ise. (C) 1998 Federation of European Biochemical Societies.