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首页> 外文期刊>American Journal of Physiology >Enhanced oxidative stress in kidneys of salt-sensitive hypertension: role of sensory nerves.
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Enhanced oxidative stress in kidneys of salt-sensitive hypertension: role of sensory nerves.

机译：盐敏感性高血压肾脏中增强的氧化应激：感觉神经的作用。

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摘要

To determine the mechanism(s) underlying enhanced oxidative stress in kidneys of salt-sensitive hypertension, neonatal Wistar rats were given vehicle or capsaicin (CAP, 50 mg/kg sc) on the first and second days of life. After being weaned, male rats were assigned into four groups and treated for 2 wk with the following: vehicle + a normal sodium diet (NS, 0.4%, CON-NS), vehicle + a high-sodium diet (HS, 4%, CON-HS), CAP + NS (CAP-NS), and CAP + HS (CAP-HS). Systolic blood pressure was significantly increased in CAP-HS but not CAP-NS or CON-HS rats. Plasma and urinary 8-iso-prostaglandin F(2alpha) levels increased by approximately 40% in CON-HS and CAP-HS rats compared with their respective controls fed a NS diet (P < 0.05), and these parameters were higher in CAP-HS compared with CON-HS rats. Superoxide (O(2)(-)*) levels in the renal cortex and medulla increased by approximately 45% in CAP-HS compared with CON-HS, CON-NS, and CAP-NS rats (P < 0.05). Enhanced O(2)(-)* levels in the cortex and medulla inCAP-HS rats were prevented by preincubation of renal tissues with apocynin, a selective NAD(P)H oxidase inhibitor. Protein expression of NAD(P)H oxidase subunits, including p47(phox) and gp91(phox) in the renal cortex and medulla, was significantly increased in CAP-HS compared with CON-HS, CON-NS, and CAP-NS rats. In contrast, protein expression and activities of Cu/Zn SOD and Mn SOD were significantly increased in the renal medulla in both CAP-HS and CON-HS but in the cortex in CAP-HS rats only. Creatinine clearance decreased by approximately 45% in CAP-HS rats compared with CON-HS, CON-NS, and CAP-NS rats (P < 0.05). O(2)(-)* levels in the renal cortex of CAP-HS rats negatively correlated with creatinine clearance (r = -0.76; P < 0.001). Therefore, regardless of enhanced SOD activity to suppress oxidative stress, increased oxidative stress in the kidney of CAP-treated rats fed a HS diet is likely the result of increased expression and activities of NAD(P)H oxidase, which may contribute to decreased renal function and increased blood pressure in these rats. Our results suggest that sensory nerves may play a compensatory role in attenuating renal oxidative stress during HS intake.
机译：为了确定盐敏感性高血压肾脏中氧化应激增强的潜在机制，新生Wistar大鼠在生命的第一天和第二天就被给予了载体或辣椒素（CAP，50 mg / kg sc）。断奶后，将雄性大鼠分为四组，并用以下方法治疗2周：赋形剂+正常钠饮食（NS，0.4％，CON-NS），赋形剂+高钠饮食（HS，4％， CON-HS），CAP + NS（CAP-NS）和CAP + HS（CAP-HS）。 CAP-HS大鼠的收缩压显着升高，而CAP-NS或CON-HS大鼠则没有。 CON-HS和CAP-HS大鼠的血浆和尿中的8-iso-前列腺素F（2alpha）水平与其分别饲喂NS饮食的对照组相比增加了约40％（P <0.05），并且这些参数在CAP-HS中更高HS与CON-HS大鼠相比。与CON-HS，CON-NS和CAP-NS大鼠相比，CAP-HS中肾皮质和髓质中的超氧化物（O（2）（-）*）水平增加了约45％（P <0.05）。 CAP-HS大鼠皮层和髓质中增强的O（2）（-）*水平可通过将Apocynin（一种选择性的NAD（P）H氧化酶抑制剂）预先孵育肾组织来预防。与CON-HS，CON-NS和CAP-NS大鼠相比，CAP-HS中NAD（P）H氧化酶亚基（包括p47（phox）和gp91（phox））在肾皮质和髓质中的蛋白表达显着增加。 。相反，在CAP-HS和CON-HS中，肾髓质中的蛋白质表达和Cu / Zn SOD和Mn SOD活性均显着增加，而仅在CAP-HS大鼠中皮质中。与CON-HS，CON-NS和CAP-NS大鼠相比，CAP-HS大鼠的肌酐清除率降低了约45％（P <0.05）。 CAP-HS大鼠肾皮质中O（2）（-）*水平与肌酐清除率负相关（r = -0.76; P <0.001）。因此，无论增强SOD活性以抑制氧化应激，喂食HS饮食的CAP治疗的大鼠肾脏中氧化应激的增加很可能是NAD（P）H氧化酶表达和活性增加的结果，这可能导致肾脏减少这些大鼠的功能和血压升高。我们的研究结果表明，感觉神经可能在HS摄入期间在减轻肾脏氧化应激中起补偿作用。

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