ADMA对交感神经损毁自发性高血压大鼠血压和肾功能的作用

目的:探讨不对称二甲基精氨酸(ADMA)对交感神经损毁自发性高血压大鼠(SHR)血压和肾功能的作用。方法:新生雄性SHR随机分成交感神经损毁组和对照组,采用单硫酸胍乙啶损毁新生SHR的交感神经。12周后测量常温下鼠尾血压;代谢笼法收集大鼠尿液,检测去甲肾上腺素(NE)排泄量;高效液相色谱法检测肾脏NE和ADMA含量;比色法检测大鼠肾脏一氧化氮(NO)含量;Western blot法测定内皮型一氧化氮合酶(e NOS)的表达;通过检测肾小球滤过率(GFR)评价肾脏功能。结果:与对照组相比,交感神经损毁组尿NE排泄量以及肾脏NE和ADMA含量均明显降低,肾脏NO含量和e NOS表达显著升高,收缩压和舒张压明显降低(P0.05),24 h尿微量白蛋白、尿钠量和GFR未见明显差异。结论:抑制交感神经系统可引起ADMA和NE释放减少,NO合成和e NOS表达升高,从而对血压产生调节作用;但交感神经系统对ADMA生成的调控并不是通过影响肾脏功能来实现的。

Effect of asymmetric dimethylarginine on blood pressure and renal function in sympathectomized spontaneously hypertensive rats

AIM: To investigate the effect of asymmetric dimethylarginine (ADMA) on blood pressure and renal function in sympathectomized spontaneously hypertensive rats (SHR). METHODS: The neonatal SHR were sympathectomized by guanethidine monosulfate. Systolic and diastolic blood pressure was monitored by tail-cuff method. Urine excretion of norepinephrine (NE) was measured by metabolic cage collection. The levels of ADMA and NE in the kidneys were analyzed by HPLC. Nitric oxide (NO) content in SHR kidney was detected by colorimetry. The protein expression of endothelial nitric oxide synthase (eNOS) was determined by Western blot. Glomerular filtration rate (GFR) was examined to evaluate the renal function. RESULTS: Neonatal chemical sympathectomy produced significant decreases in urinary NE excretion, renal NE and ADMA contents, and systolic and diastolic blood pressure compared with the sympathetically intact SHR (P<0.05). Moreover, the level of NO content and protein expression of eNOS in the kidneys were significantly increased (P<0.05). However, no significant difference was observed in microalbumin, urinary sodium excretion and GFR between the sympathetically intact SHR and the sympathectomized SHR. CONCLUSION: Inhibition of sympathetic nervous system affects blood pressure by reducing the release of ADMA and NE, and increasing NO synthesis and eNOS expression. The regulation of ADMA generation by sympathetic nervous system does not influence renal function.