Koba S, Watanabe R, Kano N, Watanabe T. Oxidative stress exaggerates skeletal muscle contraction-evoked reflex sympathoexcitation in rats with hypertension induced by angiotensin II. Muscle contraction stimulates thin fiber muscle afferents and evokes reflex sympathoexcitation. In hypertension, this reflex is exaggerated. ANG II, which is elevated in hypertension, has been reported to trigger the production of superoxide and other reactive oxygen species. In the present study, we tested the

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... thesis that increased ANG II in hypertension exaggerates skeletal muscle contraction-evoked reflex sympathoexcitation by inducing oxidative stress in the muscle. In rats, subcutaneous infusion of ANG II at 450 ng·kg Ϫ1 ·min Ϫ1 for 14 days significantly (P Ͻ 0.05) elevated blood pressure compared with shamoperated (sham) rats. Electrically induced 30-s hindlimb muscle contraction in decerebrate rats with hypertension evoked larger renal sympathoexcitatory and pressor responses [ϩ1,173 Ϯ 212 arbitrary units (AU) and ϩ35 Ϯ 5 mmHg, n ϭ 10] compared with sham normotensive rats (ϩ419 Ϯ 103 AU and ϩ13 Ϯ 2 mmHg, n ϭ 11). Tempol, a SOD mimetic, injected intra-arterially into the hindlimb circulation significantly reduced responses in hypertensive rats, whereas this compound had no effect on responses in sham rats. Tiron, another SOD mimetic, also significantly reduced reflex renal sympathetic and pressor responses in a subset of hypertensive rats (n ϭ 10). Generation of muscle superoxide, as evaluated by dihydroethidium staining, was increased in hypertensive rats. RT-PCR and immunoblot experiments showed that mRNA and protein for gp91 phox , a NADPH oxidase subunit, in skeletal muscle tissue were upregulated in hypertensive rats. Taken together, hese results suggest that increased ANG II in hypertension induces oxidative stress in skeletal muscle, thereby exaggerating the muscle reflex. muscle contraction; angiotensin II; oxidative stress; sympathetic nerve activity Address for reprint requests and other correspondence: S. Koba,