Ryndin Igor, Gulmi Frederick A, Chou Shyan-Yih, Mooppan Unni M M, Kim Hong
Department of Urology, Brookdale University Hospital and Medical Center, Brooklyn, New York, USA.
J Urol. 2005 Feb;173(2):651-6. doi: 10.1097/01.ju.0000150532.61780.1f.
Atrial natriuretic peptide (ANP) contributes to post-obstructive diuresis in bilateral ureteral obstruction (BUO). In this study we examined the activity of neutral endopeptidase (NEP), an enzyme responsible for degradation of ANP, in the kidney in rats subjected to BUO for 24 hours.
Renal function was examined by the clearance method in sham operated rats and BUO rats after obstruction release. Renal responses to an intravenous bolus injection of ANP (5 microg/kg) were studied in sham operated and BUO rats with or without pretreatment with intravenous phosphoramidon (100 microg/kg per minute), a NEP inhibitor.
In BUO rats natriuresis and diuresis occurred despite a marked decrease in the glomerular filtration rate (GFR). ANP administration increased GFR and induced marked natriuresis and diuresis in sham operated and BUO rats. Inhibition of ANP degradation by phosphoramidon induced natriuresis and diuresis, and accentuated these renal responses to ANP.
Renal responses to ANP and renal NEP activity were preserved in 24-hour BUO. NEP inhibition to attenuate ANP degradation augmented responses to ANP in increasing GFR, natriuresis and diuresis. These findings provide the theoretical potential for facilitating the recovery of GFR after BUO release by inhibiting ANP degradation by pharmacological means.
心房利钠肽（ANP）有助于双侧输尿管梗阻（BUO）后的梗阻解除后利尿。在本研究中，我们检测了在经历24小时BUO的大鼠肾脏中，负责降解ANP的中性内肽酶（NEP）的活性。
通过清除率法检测假手术大鼠和梗阻解除后的BUO大鼠的肾功能。在假手术大鼠和BUO大鼠中，研究静脉推注ANP（5微克/千克）后的肾脏反应，其中部分大鼠在注射前静脉给予NEP抑制剂磷酰胺素（每分钟100微克/千克）进行预处理。
在BUO大鼠中，尽管肾小球滤过率（GFR）显著降低，但仍出现了利钠和利尿现象。给予ANP可增加GFR，并在假手术大鼠和BUO大鼠中诱导显著的利钠和利尿。磷酰胺素抑制ANP降解可诱导利钠和利尿，并增强这些肾脏对ANP的反应。
在24小时BUO中，肾脏对ANP的反应和肾脏NEP活性得以保留。抑制NEP以减弱ANP降解可增强对ANP在增加GFR、利钠和利尿方面的反应。这些发现为通过药理学手段抑制ANP降解来促进BUO解除后GFR的恢复提供了理论潜力。
