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

¹ Menzies Research Institute, University of Tasmania, Hobart, Tasmania, 7001, Australia
² Department of Physiology, The University of Melbourne, Parkville, Victoria, 3010, Australia

Objective: We have shown previously 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, studies in rodents 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 a 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, then one hindleg electrically stimulated to contract (2Hz, 0.1ms) 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 5µM) 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 35%, without affecting AMPK activation.

Conclusions: NOS inhibition attenuated increases in skeletal muscle glucose uptake during contraction without influencing capillary recruitment suggesting that nitric oxide is critical for part of the normal increase in skeletal muscle fiber glucose uptake during contraction.

Key Words: Nitric oxide • AMPK • blood flow • glucose uptake

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