NITRIC-OXIDE MEDIATES CONTRACTION-INDUCED ATTENUATION OF SYMPATHETIC VASOCONSTRICTION IN RAT SKELETAL-MUSCLE

1. Sympathetic vasoconstriction is attenuated by metabolic events in c ontracting rat skeletal muscle, in part by activation of ATP-sensitive potassium (K-ATP) channels. However, the specific metabolites in cont racting muscle that open K-ATP channels are not known. We therefore as ked if contraction-induced attenuation of sympathetic vasoconstriction is mediated by the endogenous vasodilators nitric oxide (NO), adenosi ne, or prostaglandins PGI(2) or PGE(2), all of which are putative K-AT P channel openers. 2. In anaesthetized rats, hindlimb contraction alon e significantly attenuated the vasoconstrictor responses to lumbar sym pathetic nerve stimulation. Inhibition of NO synthase with N-nitro-L-a rginine methyl ester (L-NAME, 5 mg kg(-1), I.V.) partially reversed th is effect of contraction, resulting in enhanced sympathetic vasoconstr iction in contracting hindlimb. Subsequent treatment with the K-ATP ch annel blocker glibenclamide (20 mg kg(-1), I.V.) had no further effect on sympathetic vasoconstriction in contracting hindlimb. 3. This effe ct of L-NAME to partially reverse contraction-induced attenuation of s ympathetic vasoconstriction was not replicated by D-NAME (5 mg kg(-1), I.V.) or angiotensin II (12.5 ng kg(-1) min(-1), I.V.), the latter us ed as a hypertensive control. 4. Adenosine receptor blockade with 8-(p -sulphophenyl)theophylline (10 mg kg(-1), I.V.) or cyclooxygenase inhi bition with indomethacin (5 mg kg(-1), I.V.) had no effect on contract ion-induced attenuation of sympathetic vasoconstriction. 5. These resu lts suggest that NO plays an important role in the precise regulation of blood flow in exercising skeletal muscles by opposing sympathetic v asoconstriction. Although the underlying mechanism is not known, it ma y involve NO-induced activation of vascular K-ATP channels.