Division of Integrative Physiology, Tottori University Faculty of Medicine, 86 Nishi-cho, Yonago, Tottori, Japan.
Am J Physiol Heart Circ Physiol. 2013 Jan 1;304(1):H142-53. doi: 10.1152/ajpheart.00423.2012. Epub 2012 Oct 19.
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 hypothesis 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(-1)·min(-1) for 14 days significantly (P < 0.05) elevated blood pressure compared with sham-operated (sham) rats. Electrically induced 30-s hindlimb muscle contraction in decerebrate rats with hypertension evoked larger renal sympathoexcitatory and pressor responses [+1,173 ± 212 arbitrary units (AU) and +35 ± 5 mmHg, n = 10] compared with sham normotensive rats (+419 ± 103 AU and +13 ± 2 mmHg, n = 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 = 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.
肌肉收缩刺激细纤维肌传入神经，并引起反射性交感兴奋。在高血压中，这种反射被夸大。已经报道，在高血压中升高的血管紧张素 II（ANG II）触发超氧化物和其他活性氧物质的产生。在本研究中，我们检验了以下假设：高血压中升高的 ANG II 通过在肌肉中诱导氧化应激，夸大了骨骼肌收缩引起的反射性交感兴奋。在大鼠中，皮下输注 ANG II 450 ng·kg(-1)·min(-1) 14 天，与假手术（sham）大鼠相比，显著（P < 0.05）升高血压。患有高血压的去大脑大鼠电刺激 30 秒后，后肢肌肉收缩引起的肾脏交感神经兴奋性和升压反应更大[+1,173 ± 212 个任意单位（AU）和+35 ± 5 mmHg，n = 10]，与 sham 正常血压大鼠[+419 ± 103 AU 和+13 ± 2 mmHg，n = 11]相比。Tempol，一种 SOD 模拟物，经股动脉内注射到后肢循环中，显著降低高血压大鼠的反应，而该化合物对 sham 大鼠的反应没有影响。另一种 SOD 模拟物 Tiron 也显著降低了一组高血压大鼠的反射性肾交感神经和升压反应（n = 10）。通过二氢乙啶染色评估，肌肉中超氧化物的产生增加。RT-PCR 和免疫印迹实验显示，骨骼肌组织中 gp91(phox)的 mRNA 和蛋白，一种 NADPH 氧化酶亚基，在高血压大鼠中上调。总之，这些结果表明，高血压中升高的 ANG II 诱导骨骼肌中的氧化应激，从而夸大了肌肉反射。
