1. Sympathetic vasconstriction is attenuated by metabolic events in contracting rat skeletal muscle, in part by activation of ATP-sensitive potassium (K(ATP)) channels. However, the specific metabolites in contracting muscle that open K(ATP) channels are not known. We therefore asked if contraction-induced attenuation of sympathetic vasoconstriction is mediated by the endogenous vasodilators nitric oxide (NO), adenosine, or prostaglandins PGI2 or PGE2, all of which are putative K(ATP) channel openers. 2. In anaesthetizes rats, hindlimb contraction alone significantly attenuated the vasoconstrictor responses to lumbar sympathetic nerve stimulation. Inhibition of NO synthase with N-nitro-L-arginine methyl ester (L-NAME, 5 mg kg-1, I.V.) partially reversed this effect of contraction, resulting in enhanced sympathetic vasoconstriction in contracting hindlimb. Subsequent treatment with the K(ATP) channel blocker glibenclamide (20 mg kg-1, I.V.) had no further effect on sympathetic vasoconstriction in contracting hindlimb. 3. This effect of L-NAME to partially reverse contraction-induced attenuation of sympathetic 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 used as a hypertensive control. 4. Adenosine receptor blockade with 8-(p-sulphophenyl)theophylline (10 mg kg-1, I.V.) or cyclo-oxygenase inhibition with indomethacin (5 mg kg-1, I.V.) had no effect on contraction-induced attenuation of sympathetic vasoconstriction. 5. These results suggest that NO plays an important role in the precise regulation of blood flow in exercising skeletal muscles by opposing sympathetic vasoconstriction. Although the underlying mechanism is not known, it may involve NO-induced activation of vascular K(ATP) channels.
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