Gd. Thomas et Rg. Victor, NITRIC-OXIDE MEDIATES CONTRACTION-INDUCED ATTENUATION OF SYMPATHETIC VASOCONSTRICTION IN RAT SKELETAL-MUSCLE, Journal of physiology, 506(3), 1998, pp. 817-826
1. Sympathetic vasoconstriction is attenuated by metabolic events in c
ontracting rat skeletal muscle, in part by activation of ATP-sensitive
potassium (K-ATP) channels. However, the specific metabolites in cont
racting muscle that open K-ATP channels are not known. We therefore as
ked if contraction-induced attenuation of sympathetic vasoconstriction
is mediated by the endogenous vasodilators nitric oxide (NO), adenosi
ne, or prostaglandins PGI(2) or PGE(2), all of which are putative K-AT
P channel openers. 2. In anaesthetized rats, hindlimb contraction alon
e significantly attenuated the vasoconstrictor responses to lumbar sym
pathetic nerve stimulation. Inhibition of NO synthase with N-nitro-L-a
rginine methyl ester (L-NAME, 5 mg kg(-1), I.V.) partially reversed th
is effect of contraction, resulting in enhanced sympathetic vasoconstr
iction in contracting hindlimb. Subsequent treatment with the K-ATP ch
annel blocker glibenclamide (20 mg kg(-1), I.V.) had no further effect
on sympathetic vasoconstriction in contracting hindlimb. 3. This effe
ct of L-NAME to partially reverse contraction-induced attenuation of s
ympathetic 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 us
ed as a hypertensive control. 4. Adenosine receptor blockade with 8-(p
-sulphophenyl)theophylline (10 mg kg(-1), I.V.) or cyclooxygenase inhi
bition with indomethacin (5 mg kg(-1), I.V.) had no effect on contract
ion-induced attenuation of sympathetic vasoconstriction. 5. These resu
lts suggest that NO plays an important role in the precise regulation
of blood flow in exercising skeletal muscles by opposing sympathetic v
asoconstriction. Although the underlying mechanism is not known, it ma
y involve NO-induced activation of vascular K-ATP channels.