title: nNOS and eNOS modulate cGMP formation and vascular response in contracting fast-twitch skeletal muscle.
abstract: Nitric oxide (NO) from Ca(2+)-dependent neuronal nitric oxide synthase (nNOS) in skeletal muscle fibers may modulate vascular tone by a cGMP-dependent pathway similar to NO derived from NOS in endothelial cells (eNOS). In isolated fast-twitch extensor digitorum longus (EDL) muscles from control mice, cGMP formation increased approximately 166% with electrical stimulation (30 Hz, 15 s). cGMP levels were not altered in slow-twitch soleus muscles. The NOS inhibitor N(omega)-nitro-l-arginine abolished the contraction-induced increase in cGMP content in EDL muscles, and the NO donor sodium nitroprusside (SNP) increased cGMP content approximately 167% in noncontracting EDL muscles. SNP treatment but not electrical stimulation increased cGMP formation in muscles from nNOS(-/-) mice. cGMP formation in control and stimulated EDL muscles from eNOS(-/-) mice was less than that obtained with similarly treated muscles from control mice. Arteriolar relaxation in contracting fast-twitch mouse cremaster muscle was attenuated in muscles from mice lacking either nNOS or eNOS. These findings suggest that increases in cGMP and NO-dependent vascular relaxation in contracting fast-twitch skeletal muscle may require both nNOS and eNOS.
authors.affiliation: Department of Physiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75235-9040, USA. klau@mednet.swmed.edu
authors.forename: K S
authors.initials: KS
authors.lastname: Lau
authors.forename: R W
authors.initials: RW
authors.lastname: Grange
authors.forename: E
authors.initials: E
authors.lastname: Isotani
authors.forename: I H
authors.initials: IH
authors.lastname: Sarelius
authors.forename: K E
authors.initials: KE
authors.lastname: Kamm
authors.forename: P L
authors.initials: PL
authors.lastname: Huang
authors.forename: J T
authors.initials: JT
authors.lastname: Stull
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000502:physiology; D015153:Blotting, Western; D006152:Cyclic GMP / Q000096:biosynthesis*; D004558:Electric Stimulation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000502:physiology*; D018656:Muscle Fibers, Fast-Twitch / Q000502:physiology; D018657:Muscle Fibers, Slow-Twitch / Q000502:physiology; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III
chemical_list: D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496321:Nos1 protein, mouse; C496315:Nos3 protein, mouse; D006152:Cyclic GMP