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

被引:71
作者
Thomas, GD
Hansen, J
Victor, RG
机构
[1] Department of Internal Medicine, Molecular Cardiology Laboratories, Univ. Texas Southwestern Med. Ctr., Dallas
[2] University of Texas, Southwestern Medical Center, Dallas, TX 75235-8573
关键词
sympathetic nervous system; alpha(2) adrenergic vasoconstriction; muscle contraction; muscle blood flow; glibenclamide;
D O I
10.1172/JCI119448
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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 alpha(2)-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 now responses to lumbar sympathetic nerve stimulation or intraarterial hindlimb infusion of the specific alpha(2)-adrenergic agonist UR 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.
引用
收藏
页码:2602 / 2609
页数:8
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