Impaired metabolic modulation of alpha-adrenergic vasoconstriction in dystrophin-deficient skeletal muscle

The neuronal isoform of nitric oxide synthase (nNOS) is highly expressed in mammalian skeletal muscle, but its functional role has not been defined. N O has been implicated in the local metabolic regulation of blood flow in co ntracting skeletal muscle in part by antagonizing sympathetic vasoconstrict ion. We therefore hypothesized that nNOS in skeletal muscle is the source o f the NO mediating the inhibition of sympathetic vasoconstriction in contra cting muscle. In the mdr mouse, a model of Duchenne muscular dystrophy in w hich dystrophin deficiency results in greatly reduced expression of nNOS in skeletal muscle, we found that the normal ability of skeletal muscle contr action to attenuate alpha-adrenergic vasoconstriction is defective. Similar results were obtained in mutant mice that lack the gene encoding nNOS. Tog ether these data suggest a specific role for nNOS in the local metabolic in hibition of cu-adrenergic vasoconstriction in active skeletal muscle.