ATP-SENSITIVE POTASSIUM CHANNELS MEDIATE CONTRACTION-INDUCED ATTENUATION OF SYMPATHETIC VASOCONSTRICTION IN RAT SKELETAL-MUSCLE

Sympathetic vasoconstriction is sensitive to inhibition by metabolic e vents in contracting rat and human skeletal muscle, but the underlying cellular mechanisms are unknown. In rats, this inhibition involves ma inly alpha(2)-adrenergic vasoconstriction, which relies heavily on Ca2 + influx through voltage-dependent Ca2+ channels. We therefore hypothe sized that contraction-induced inhibition of sympathetic vasoconstrict ion is mediated by ATP-sensitive potassium (K-ATP) channels, a hyperpo larizing vasodilator mechanism that could be activated by some metabol ic product(s) of skeletal muscle contraction. We tested this hypothesi s in anesthetized rats by measuring femoral artery blood now responses to lumbar sympathetic nerve stimulation or intraarterial hindlimb inf usion of the specific alpha(2)-adrenergic agonist UR 14,304 during K-A TP channel activation with diazoxide in resting hindlimb and during K- ATP channel block with glibenclamide in contracting hindlimb. The majo r new findings are twofold. First, like muscle contraction, pharmacolo gic activation of K-ATP channels with diazoxide in resting hindlimb do se dependently attenuated the vasoconstrictor responses to either symp athetic nerve stimulation or intraarterial UK 14,304. Second, the larg e contraction-induced attenuation in sympathetic vasoconstriction elic ited by nerve stimulation or UK 14,304 was partially reversed when the physiologic activation of K-ATP channels produced by muscle contracti on was prevented with glibenclamide. We conclude that contraction-indu ced activation of K-ATP channels is a major mechanism underlying metab olic inhibition of sympathetic vasoconstriction in exercising skeletal muscle.