Gd. Thomas et al., ATP-SENSITIVE POTASSIUM CHANNELS MEDIATE CONTRACTION-INDUCED ATTENUATION OF SYMPATHETIC VASOCONSTRICTION IN RAT SKELETAL-MUSCLE, The Journal of clinical investigation, 99(11), 1997, pp. 2602-2609
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.