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首页> 外文期刊>American Journal of Physiology >Overexpression of kidney neutral endopeptidase (EC 3.4.24.11) and renal function in experimental cirrhosis.
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Overexpression of kidney neutral endopeptidase (EC 3.4.24.11) and renal function in experimental cirrhosis.

机译：实验性肝硬化中肾脏中性内肽酶的过表达（EC 3.4.24.11）和肾功能。

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Neutral endopeptidase degrades atrial natriuretic peptide (ANP) and bradykinin and may generate endothelin-1 from big-endothelin. In advanced cirrhosis, sodium retention is accompanied by elevated plasma ANP levels, and infusion of ANP causes hypotension, but in normal humans increasing the concentration of ANP through the inhibition of neutral endopeptidase, localized in renal proximal tubule cells, causes natriuresis without any arterial pressure drop. The purpose of this study was the assessment of kidney neutral endopeptidase expression and responses to candoxatrilat (a specific inhibitor of this enzyme) in rats with CCl4-induced cirrhosis. Two groups of control rats (n = 5) were injected with vehicle or 3 mg/kg candoxatrilat. Three groups of cirrhotic rats with ascites (n = 10) received vehicle alone or 3 or 10 mg/kg candoxatrilat. In cirrhotic rats, Western blot analysis revealed a 170% increase in renal neutral endopeptidase protein content (P < 0.03), mainly in the proximal nephron and macula densa, and both candoxatrilat dosages increased plasma ANP levels, urinary volume, and urinary excretion of sodium, ANP, and cGMP compared with vehicle alone (all P < 0.03). Candoxatrilat (10 mg/kg) also reduced tubular solute-free water reabsorption (P < 0.03) in cirrhotic rats, but renal blood flow, arterial pressure, and plasma renin activity were unaffected. Neutral endopeptidase inhibition has natriuretic and aquaretic actions in cirrhosis without any effect on blood pressure and kidney perfusion due to a significant overexpression of this enzyme in renal cortex.
机译：中性内肽酶降解心钠素和缓激肽，并可能从大内皮素生成内皮素-1。在晚期肝硬化中，钠retention留伴随着血浆ANP水平升高，而输注ANP会引起低血压，但在正常人中，通过抑制位于肾近端小管细胞中的内肽酶增加ANP的浓度，会导致钠尿而无任何动脉压下降。这项研究的目的是评估在CCl4诱导的肝硬化大鼠中肾中性内肽酶的表达和对candoxatrilat（该酶的特异性抑制剂）的反应。两组对照组大鼠（n = 5）注射媒介物或3 mg / kg的candoxatrilat。三组腹水性肝硬化大鼠（n = 10）单独接受溶媒或3或10 mg / kg的candoxatrilat。在肝硬化大鼠中，Western blot分析显示，肾脏中性内肽酶蛋白含量增加了170％（P <0.03），主要在近端肾和黄斑区，并且两种candoxatrilat剂量均可增加血浆ANP水平，尿液量和钠的尿排泄量，ANP和cGMP与单独的媒介相比（所有P <0.03）。 Candoxatrilat（10 mg / kg）还可减少肝硬化大鼠的肾小管内无溶质的水重吸收（P <0.03），但肾血流量，动脉压和血浆肾素活性未受影响。中性内肽酶抑制作用在肝硬化中具有利尿和水生作用，但由于该酶在肾皮质中的显着过表达而对血压和肾脏灌注没有任何影响。

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