Local nitric oxide synthase inhibition reduces skeletal muscle glucose uptake but not capillary blood flow during in situ muscle contraction in rats

Diabetes. 2007 Dec;56(12):2885-92. doi: 10.2337/db07-0745. Epub 2007 Sep 19.


Objective: We have previously shown in humans that local infusion of a nitric oxide synthase (NOS) inhibitor into the femoral artery attenuates the increase in leg glucose uptake during exercise without influencing total leg blood flow. However, rodent studies examining the effect of NOS inhibition on contraction-stimulated skeletal muscle glucose uptake have yielded contradictory results. This study examined the effect of local infusion of an NOS inhibitor on skeletal muscle glucose uptake (2-deoxyglucose) and capillary blood flow (contrast-enhanced ultrasound) during in situ contractions in rats.

Research design and methods: Male hooded Wistar rats were anesthetized and one hindleg electrically stimulated to contract (2 Hz, 0.1 ms) for 30 min while the other leg rested. After 10 min, the NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) (arterial concentration of 5 micromol/l) or saline was infused into the epigastric artery of the contracting leg.

Results: Local NOS inhibition had no effect on blood pressure, heart rate, or muscle contraction force. Contractions increased (P < 0.05) skeletal muscle NOS activity, and this was prevented by L-NAME infusion. NOS inhibition caused a modest significant (P < 0.05) attenuation of the increase in femoral blood flow during contractions, but importantly there was no effect on capillary recruitment. NOS inhibition attenuated (P < 0.05) the increase in contraction-stimulated skeletal muscle glucose uptake by approximately 35%, without affecting AMP-activated protein kinase (AMPK) activation.

Conclusions: NOS inhibition attenuated increases in skeletal muscle glucose uptake during contraction without influencing capillary recruitment, suggesting that NO is critical for part of the normal increase in skeletal muscle fiber glucose uptake during contraction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Flow Velocity / physiology*
  • Capillaries / physiology*
  • Enzyme Inhibitors / pharmacology*
  • Glucose / metabolism*
  • Male
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology*
  • Muscle, Skeletal / blood supply*
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism*
  • NG-Nitroarginine Methyl Ester / pharmacology*
  • Nitric Oxide / physiology
  • Nitric Oxide Synthase Type III / antagonists & inhibitors*
  • Rats
  • Rats, Wistar


  • Enzyme Inhibitors
  • Nitric Oxide
  • Nitric Oxide Synthase Type III
  • Glucose
  • NG-Nitroarginine Methyl Ester