ATP-sensitive potassium channels mediate contraction-induced attenuation of sympathetic vasoconstriction in rat skeletal muscle

Gail D. Thomas, Jim Hansen, Ronald G. Victor

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76 Scopus citations

Abstract

Sympathetic vasoconstriction is sensitive to inhibition by metabolic events in contracting rat and human skeletal muscle, but the underlying cellular mechanisms are unknown. In rats, this inhibition involves mainly α2-adrenergic vasoconstriction, which relies heavily on Ca2+ influx through voltage-dependent Ca2+ channels. We therefore hypothesized that contraction-induced inhibition of sympathetic vasoconstriction is mediated by ATP-sensitive potassium (K(ATP)) channels, a hyperpolarizing vasodilator mechanism that could be activated by some metabolic product(s) of skeletal muscle contraction. We tested this hypothesis in anesthetized rats by measuring femoral artery blood flow responses to lumbar sympathetic nerve stimulation or intraarterial hindlimb infusion of the specific α2- adrenergic agonist UK 14,304 during K(ATP) channel activation with diazoxide in resting hindlimb and during K(ATP) channel block with glibenclamide in contracting hindlimb. The major new findings are twofold. First, like muscle contraction, pharmacologic activation of K(ATP) channels with diazoxide in resting hindlimb dose dependently attenuated the vasoconstrictor responses to either sympathetic nerve stimulation or intraarterial UK 14,304. Second, the large contraction-induced attenuation in sympathetic vasoconstriction elicited by nerve stimulation or UK 14,304 was partially reversed when the physiologic activation of K(ATP) channels produced by muscle contraction was prevented with glibenclamide. We conclude that contraction-induced activation of K(ATP) channels is a major mechanism underlying metabolic inhibition of sympathetic vasoconstriction in exercising skeletal muscle.

Original languageEnglish (US)
Pages (from-to)2602-2609
Number of pages8
JournalJournal of Clinical Investigation
Volume99
Issue number11
DOIs
StatePublished - Jun 1 1997

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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