nNOS and eNOS modulate cGMP formation and vascular response in contracting fast-twitch skeletal muscle

Kim S. Lau, Robert W. Grange, Eiji Isotani, Ingrid H. Sarelius, Kristine E. Kamm, Paul L. Huang, James T. Stull

Research output: Contribution to journalArticlepeer-review

131 Scopus citations


Nitric oxide (NO) from Ca2+-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 ∼166% with electrical stimulation (30 Hz, 15 s). cGMP levels were not altered in slow-twitch soleus muscles. The NOS inhibitor Nω-nitro-L-arginine abolished the contraction-induced increase in cGMP content in EDL muscles, and the NO donor sodium nitroprusside (SNP) increased cGMP content ∼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.

Original languageEnglish (US)
Pages (from-to)21-27
Number of pages7
JournalPhysiological genomics
Issue number2
StatePublished - May 2000


  • Arteriolar relaxation
  • Endothelial nitric oxide synthase
  • Neuronal nitric oxide synthase

ASJC Scopus subject areas

  • Physiology
  • Genetics


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