Oxidative stress and the muscle reflex in heart failure
Oxidative stress and the muscle reflex in heart failure
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DOI：
10.1113/jphysiol.2009.177071
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发表时间：
2009-11-01
影响因子：
5.5
通讯作者：
Sinoway, Lawrence I.
中科院分区：
文献类型：
--
作者：
Koba, Satoshi;Gao, Zhaohui;Sinoway, Lawrence I.
肌肉收缩刺激细纤维肌肉传入并引起血压反射性升高。在心力衰竭 (HF) 中，这种反射会加剧。值得注意的是，HF 中的超氧化物和其他活性氧物质会增加。在这份报告中，我们测试了这样的假设：过量的超氧化物会导致心力衰竭时肌肉反射过度。通过冠状动脉结扎诱发大鼠心力衰竭。与对照大鼠（FS = 47 +/- 1%；n = 14）相比，电诱导去脑心肌梗死（MI）大鼠的 30 秒后肢肌肉收缩（左心室缩短分数（FS）= 24 +/- 1%；n = 15）引起平均动脉压（MAP）和肾交感神经活动（RSNA）更大（P < 0.05）增加。在 MI 大鼠中，通过动脉内注射 tempol（10 mg）（一种超氧化物歧化酶模拟物）后肢循环，可降低升压和 RSNA 对收缩的反应（δ MAP：22 +/- 2 与 11 +/- 1 mmHg；积分 δ RSNA：1032 +/- 204 与 431 +/- 73 任意单位 (a.u.)；tempol 之前与之后；P < 0.05）。 Tempol 还减弱了 MI 大鼠中 1 分钟间歇性（1-4 秒刺激至放松）静态收缩的 RSNA 反应（116 +/- 17 vs. 72 +/- 11 a.u.；P < 0.05；n = 16）。在对照大鼠中，tempol 对这些反应没有影响。这些结果表明，高频中过量的超氧化物会使收缩过程中参与的机械敏感肌肉传入变得敏感。我们假设氧化应激导致心力衰竭时肌肉反射过度。
Muscle contraction stimulates thin fibre muscle afferents and evokes a reflex increase in blood pressure. In heart failure (HF) this reflex is accentuated. Of note, superoxide and other reactive oxygen species are increased in HF. In this report, we tested the hypothesis that excess superoxide contributes to the exaggerated muscle reflex in HF. HF was induced in rats by coronary artery ligation. Electrically induced 30 s hindlimb muscle contraction in decerebrate rats with myocardial infarction (MI) (left ventricular fractional shortening (FS) = 24 +/- 1%; n = 15) evoked larger (P < 0.05) increases in mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) as compared to control rats (FS = 47 +/- 1%; n = 14). In the MI rats, the pressor and RSNA responses to contraction were reduced by intra-arterial injection into the hindlimb circulation of tempol (10 mg), a superoxide dismutase mimetic (delta MAP: 22 +/- 2 vs. 11 +/- 1 mmHg; integral delta RSNA: 1032 +/- 204 vs. 431 +/- 73 arbitrary units (a.u.); before vs. after tempol; P < 0.05). Tempol also attenuated the RSNA response to 1 min intermittent (1-4 s stimulation to relaxation) bouts of static contraction in the MI rats (116 +/- 17 vs. 72 +/- 11 a.u.; P < 0.05; n = 16). In the control rats, tempol had no effect on these responses. These results suggest that excess superoxide in HF sensitizes mechanically sensitive muscle afferents engaged during contraction. We hypothesize that oxidative stress contributes to the exaggerated muscle reflex in HF.