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Abstract
Maximum velocity of shortening, V^sub 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^sub o^ by 18% and 22%, respectively. On removal of the inhibitor, V^sub 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^sub o^. A donor of nitric oxide, 0.1 mM nitroprusside, increased V^sub 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^sub o^ by 8%. An inhibitor of cGMP synthase, 0.01 mM Ly-83583, decreased V^sub o^ by 18%. An analogue of cGMP, 0.1 mM 8-bromo-cGMP, increased V^sub o^ by 17%. A general inhibitor of phosphodiesterases, 0.02 mM 3-isobutyl-1-methylxanthine (IBMX), increased V^sub o^ by 17%. An inhibitor specific of cGMP phosphodiesterase, 0.01 mM dipyridamole, increased V^sub o^ by 8%. The maximal isometric force (F^sub 0^) was not modified by the drugs, except by 7-nitroindazole and Ly-83583, which depressed F^sub 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^sub o^through thecGMP pathway.[PUBLICATION ABSTRACT]