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

Abstract

Maximum velocity of shortening, Vo, 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 degreesC. Blockers of nitric oxide synthase, 10 mM nitro-l-arginine or 1 mM 7-nitroindazole, reduced Vo by 18% and 22%, respectively. On removal of the inhibitor, Vo 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 Vo. A donor of nitric oxide, 0.1 mM nitroprusside, increased Vo by 15%. It removed the inhibition caused by nitro-l-arginine. Another donor of nitric oxide, 1 microM (+/-)-S-nitroso-N-acetylpenicillamine (SNAP), increased Vo by 8%. An inhibitor of cGMP synthase, 0.01 mM Ly-83583, decreased Vo by 18%. An analogue of cGMP, 0.1 mM 8-bromo-cGMP, increased Vo by 17%. A general inhibitor of phosphodiesterases, 0.02 mM 3-isobutyl-1-methylxanthine (IBMX), increased Vo by 17%. An inhibitor specific of cGMP phosphodiesterase, 0.01 mM dipyridamole, increased Vo by 8%. The maximal isometric force (F0) was not modified by the drugs, except by 7-nitroindazole and Ly-83583, which depressed F0 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 Vo through the cGMP pathway.

Non-Cholinergic Signaling Pathways at Vertebrate Neuromuscular Junctions

“…This did not happen, when the donor of NO was added together with the blocker of enzyme. Similar results were obtained also on mouse extensor digitorum longus [148]. Interesting data is presented in [149], where it is shown that L-arginine (the substrate for the NO synthesis) increases the amplitude of muscle contraction in response to nerve stimulation of isolated rat diaphragm, but it leads to a reduction at direct muscles stimulation.…”

Change in contractile properties of human muscle in relationship to the loss of power and slowing of relaxation seen with fatigue

“…Another possibility is a mechanism similar to that described by Maréchal & Beckers-Bleukx (1998) and Zhu et al (2003), associated with the production of NO.…”

Inorganic nitrate supplementation improves muscle oxygenation, O2uptake kinetics, and exercise tolerance at high but not low pedal rates

“…Importantly, increasing the intake of dietary inorganic nitrate (NO 3 Ϫ ), which passes into the enterosalivary circulation for subsequent reduction to NO 2 Ϫ by oral anaerobes (19), has been shown to positively impact NO biomarkers, exercise efficiency, and exercise tolerance in recreationally active subjects (3,4,12,42,43,58,61). Therefore, supplementation with NO 3 Ϫ appears to represent an effective dietary intervention to improve NO bioavailability, contractile efficiency, and fatigue resistance.Results from in vitro studies suggest that the influence of NO on mammalian skeletal muscle contractility is impacted by contraction frequency (5,20,46,49). Hernandez et al (34) harvested single flexor digitorum brevis (FDB) muscle fibers from NO 3 Ϫ -supplemented mice and reported increased in vitro contractile force up to 50 Hz stimulation and a more rapid rate of force development in the single FDB muscle fibers at 100 Hz stimulation.…”

“…Results from in vitro studies suggest that the influence of NO on mammalian skeletal muscle contractility is impacted by contraction frequency (5,20,46,49). Hernandez et al (34) harvested single flexor digitorum brevis (FDB) muscle fibers from NO 3 Ϫ -supplemented mice and reported increased in vitro contractile force up to 50 Hz stimulation and a more rapid rate of force development in the single FDB muscle fibers at 100 Hz stimulation.…”