Endothelial Dysfunction and Increased Responses to Renal Nerve Stimulation in Rat Kidneys during Rhabdomyolysis-Induced Acute Renal Failure: Role of Hydroxyl Radical
Endothelial Dysfunction and Increased Responses to Renal Nerve Stimulation in Rat Kidneys during Rhabdomyolysis-Induced Acute Renal Failure: Role of Hydroxyl Radical
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DOI：
10.3109/0886022x.2011.643389
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发表时间：
2012-01-01
期刊：
影响因子：
3
通讯作者：
Onur, Rustu
中科院分区：
文献类型：
--
作者：
Cil, Onur;Ertunc, Mert;Onur, Rustu
横纹肌溶解是急性肾功能衰竭（ARF）的重要病因，肾血管收缩是ARF发病的主要机制。羟基自由基引起的脂质过氧化。OH)的形成和肌红蛋白的氧化还原循环也起作用。我们研究了肾血管反应性的紊乱，以揭示导致ARF的机制。雌性Wistar大鼠（n = 7）肌内注射甘油（10 mL/kg， 50%生理盐水）诱导横纹肌溶解，然后分离肾脏并灌注。我们研究了乙酰胆碱（ACh）诱导的内皮依赖性和罂粟碱（PAP）诱导的内皮依赖性血管舒张反应和肾神经刺激（RNS）诱导的血管收缩。在接受任何一种治疗的大鼠中也进行了研究。OH清除剂二甲基硫脲（DMTU：注射甘油前500 mg/kg，注射甘油后8 h 125 mg/kg， n = 7）或肌红蛋白氧化还原循环抑制剂对乙酰氨基酚（ApAP：注射甘油前2 h 100 mg/kg，注射甘油后4 h 100 mg/kg，注射甘油后22 h， n = 7）。甘油组乙酰胆碱诱导的反应降低（p < 0.001），但pap诱导的血管舒张无变化。甘油组各肾血管收缩更大（p < 0.001）。DMTU恢复内皮依赖性血管舒张和rns诱导的血管收缩。ApAP对血管反应无影响。DMTU和ApAP对肾组织有部分保护作用，但不恢复血清肌酐和血尿素氮（BUN）水平或肌酐清除率。这项研究表明，在横纹肌溶解过程中，内皮功能障碍和血管收缩增加。OH在这些血管反应的发展中起着重要作用。这些研究结果表明，在横纹肌溶解诱发的ARF期间，内皮依赖性血管舒张的减少和肾交感神经张力的增强有助于肾血管收缩的发展。
Rhabdomyolysis is an important cause of acute renal failure (ARF) and renal vasoconstriction is the main mechanism in the pathogenesis of ARF. Lipid peroxidation due to hydroxyl radical (. OH) formation and redox cycling of myoglobin also have a role. We investigated the disturbance in renal vascular reactivity to reveal the mechanisms leading to ARF. Female Wistar rats (n = 7) were injected with glycerol (10 mL/kg, 50% in saline) intramuscularly to induce rhabdomyolysis, and then the kidneys were isolated and perfused. We investigated acetylcholine (ACh)-induced endothelium-dependent and papaverine (PAP)-induced endothelium-independent vasodilation responses and renal nerve stimulation (RNS)-induced vasoconstrictions. These were also investigated both in rats which received either. OH scavenger, dimethylthiourea (DMTU: 500 mg/kg before glycerol injection and 125 mg/kg 8 h after glycerol injection, n = 7), or myoglobin redox cycling inhibitor, acetaminophen (ApAP: 100 mg/kg 2 h before glycerol injection and 100 mg/kg each 4 h, and 22 h after glycerol injection, n = 7). ACh-induced responses in glycerol group were decreased (p < 0.001), but PAP-induced vasodilation did not change. RNS-induced vasoconstriction in all kidneys was greater (p < 0.001) in glycerol group. DMTU restored both endothelium-dependent vasodilation and RNS-induced vasoconstriction. ApAP had no effect on vascular responses. Both DMTU and ApAP exerted a partial protective effect in renal histology without restoring serum creatinine and blood urea nitrogen (BUN) levels or creatinine clearance. This study showed that endothelial dysfunction and increased vasoconstriction developed during rhabdomyolysis.. OH plays an important role in the development of these vascular responses. These findings suggest that decreased endothelium-dependent vasodilation and augmented renal sympathetic tonus contribute to the development of renal vasoconstriction during rhabdomyolysis-induced ARF.