Selective inhibition of inducible nitric oxide synthase attenuates renal ischemia and damage in experimental heatstroke
Selective inhibition of inducible nitric oxide synthase attenuates renal ischemia and damage in experimental heatstroke
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DOI：
10.1254/jphs.fp0050300
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发表时间：
2005-09-01
影响因子：
3.5
通讯作者：
Lin, MT
中科院分区：
文献类型：
--
作者：
Lee, CC;Lee, YY;Lin, MT
本研究旨在探讨预先给予选择性诱导型一氧化氮合酶(INOS)抑制剂(L)-N6(1-亚氨基乙基)赖氨酸(L-NIL)能否抑制中暑时可能发生的肾脏缺血和损伤。乌拉坦麻醉大鼠暴露于热应激(43℃)诱导中暑。对照组大鼠暴露在24摄氏度的温度下，中暑开始后，平均动脉压和肾脏血流量在接受药物治疗的中暑大鼠中都显着低于常温对照组。然而，与常温对照组相比，接受交通工具治疗的中暑大鼠的体温和肾脏损害评分都更高。治疗后中暑大鼠血浆一氧化氮(NO)、肌酐、血尿素氮(BUN)、肾组织iNOS和过氧亚硝酸盐免疫反应性均显著高于正常对照组。预先给予(L)-NIL(3 mg/kg，在热应激开始时立即静脉注射)可显著减轻中暑引起的体温升高、动脉低血压、肾脏缺血和损伤，增加肾组织诱导型一氧化氮合酶和过氧化亚硝酸根的免疫反应水平，增加血浆一氧化氮、肌酐和尿素氮的水平。因此，预处理-。服用L-Nil可显著提高中暑患者的存活率。结果提示，选择性抑制iNOS依赖的NO和过氧亚硝酸盐的形成，可通过减少高热和动脉低血压来保护中暑时的肾脏缺血和损伤。
The aim of the present study was to determine whether the possible occurrence of renal ischemia and damage during heatstroke can be suppressed by prior administration of (L)-N6(1-iminoethyl) lysine (L-NIL), a selective inducible nitric oxide synthase (iNOS) inhibitor. Urethane-anesthetized rats were exposed to heat stress (43 C degrees) to induce heatstroke. Control rats were exposed to 24 degrees C. Mean arterial pressure and renal blood flow after the onset of heatstroke both were significantly lower in vehicle-treated heatstroke rats than in normothermic controls. However, both the body temperature and renal damage scores were greater in vehicle-treated heatstroke rats compared with normothermic controls. Plasma nitric oxide (NO), creatinine, and blood urea nitrogen (BUN), as well as the renal immunoreactivity of iNOS and peroxynitrite all were significantly higher in vehicle-treated heatstroke rats compared with their normothermic controls. Pretreatment with (L)-NIL (3 mg/kg, administered intravenously and immediately at the onset of heat stress) significantly attenuated heatstroke-induced hyperthermia, arterial hypotension, renal ischemia and damage, increased renal levels of immunoreactivity of iNOS and peroxynitrite, and increased plasma levels of NO, creatinine, and BUN. Accordingly, pretreat-. ment with L-NIL significantly improved survival during heatstroke. The results suggest that selective inhibition of iNOS-dependent NO and peroxynitrite formation protects against renal ischemia and damage during heatstroke by reducing hyperthermia and arterial hypotension.