Effect of nitric oxide on the maximal velocity of shortening of a mouse skeletal muscle

Abstract

 Maximum velocity of shortening, V _o, was measured by the method of Edman [J Physiol (Lond) 291:143–159, 1979] on extensor digitorum longus muscles of a mouse in vitro at 20°C. Blockers of nitric oxide synthase, 10 mM nitro-l-arginine or 1 mM 7-nitroindazole, reduced V _o by 18% and 22%, respectively. On removal of the inhibitor, V _o returned to the control value. It was found that 10 mM nitro-d-arginine, an enantiomer of nitro-l-arginine inactive against nitric oxide synthase, did not affect V _o. A donor of nitric oxide, 0.1 mM nitroprusside, increased V _o by 15%. It removed the inhibition caused by nitro-l-arginine. Another donor of nitric oxide, 1 µM (±)-S-nitroso-N-acetylpenicillamine (SNAP), increased V _o by 8%. An inhibitor of cGMP synthase, 0.01 mM Ly-83583, decreased V _o by 18%. An analogue of cGMP, 0.1 mM 8-bromo-cGMP, increased V _o by 17%. A general inhibitor of phosphodiesterases, 0.02 mM 3-isobutyl-1-methylxanthine (IBMX), increased V _o by 17%. An inhibitor specific of cGMP phosphodiesterase, 0.01 mM dipyridamole, increased V _o by 8%. The maximal isometric force (F ₀) was not modified by the drugs, except by 7-nitroindazole and Ly-83583, which depressed F ₀ by 12%. The cGMP level in tetanized muscles decreased by 12–27% in the presence of blockers of nitric oxide synthase. We conclude that the level of intracellular nitric oxide modulates V _o through thecGMP pathway.