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Oxygen radicals impair sympathetic vasoregulation in skeletal muscle in a rat model of renovascular hypertension

Sympathetic vasoconstriction in contracting muscles normally is blunted by locally generated vasoactive substances, including muscle‐derived nitric oxide (NO). Skeletal muscle also produces reactive oxygen species (ROS), such as superoxide (O2−), which can inactivate NO. We therefore hypothesized that in conditions associated with oxidative stress, increased ROS in skeletal muscle would impair the normal contraction‐induced attenuation of sympathetic vasoconstriction. To test this, we performed experiments in rats with unilateral renal artery stenosis (2‐kidney 1‐clip model, 2K1C), which increases circulating angiotensin II and is associated with NAD(P)H oxidase‐dependent O2− production. At rest, graded lumbar sympathetic nerve stimulation decreased femoral vascular conductance (FVC) similarly in anesthetized 2K1C (n=8) and Sham (n=5) rats (ΔFVC, −33% to −77%). During hindlimb contraction, these vasoconstrictor responses were markedly attenuated, but the degree of attenuation was significantly less in the 2K1C rats (ΔFVC, −16% to −45%) versus the Sham rats (ΔFVC, −3% to −26%). In muscle from 2K1C rats, ROS were elevated and the NAD(P)H oxidase subunit gp91phox was upregulated. The O2− scavenger tempol had no effect in Sham rats, whereas it restored the normal attenuation of sympathetic vasoconstriction in the contracting hindlimbs of the 2K1C rats. Taken together, these data indicate that oxidative stress impairs sympathetic vasoregulation in contracting skeletal muscle.