Margulies K B, Cavero P G, Seymour A A, Delaney N G, Burnett J C
Mayo Clinic and Foundation, Rochester, Minnesota.
Kidney Int. 1990 Jul;38(1):67-72. doi: 10.1038/ki.1990.168.
Atrial natriuretic factor (ANF) is degraded by neutral endopeptidase. We hypothesized that neutral endopeptidase inhibition (NEP-I) increases sodium excretion and that this effect would be potentiated in the presence of an isolated increase in intrarenal ANF. In seven anesthetized dogs, ANF was infused into one renal artery to produce pathophysiologic concentrations in the supplemented kidney while the control kidney received physiologic circulating concentrations of ANF. In the control kidney, NEP-I (SQ 28,603) produced significant increases in urine flow, absolute sodium excretion and fractional sodium excretion while glomerular filtration rate (GFR) remained constant. These renal actions of NEP-I were associated with marked increases in urinary excretion of ANF and cyclic GMP consistent with decreased renal degradation and increased biologic activity of ANF. All of these effects were significantly greater in the supplemented kidney. The present study suggests that NEP-I produces natriuresis which appears to be independent of changes in GFR. In addition, while NEP-I mimics the renal action of pathophysiologic levels of ANF, NEP-I also potentiates the natriuretic effects of pathophysiologic concentrations of ANF as observed in congestive heart failure or hypertension.
心房利钠因子（ANF）可被中性内肽酶降解。我们推测，抑制中性内肽酶（NEP - I）可增加钠排泄，并且在肾内ANF单独升高的情况下，这种作用会增强。在7只麻醉犬中，将ANF注入一侧肾动脉，以使补充肾脏中产生病理生理浓度的ANF，而对照肾脏接受生理循环浓度的ANF。在对照肾脏中，NEP - I（SQ 28,603）使尿流量、绝对钠排泄量和钠排泄分数显著增加，而肾小球滤过率（GFR）保持恒定。NEP - I的这些肾脏作用与ANF和环磷酸鸟苷尿排泄量的显著增加相关，这与肾脏对ANF的降解减少和生物活性增加一致。在补充肾脏中，所有这些作用都显著更大。本研究表明，NEP - I产生利钠作用，这似乎与GFR的变化无关。此外，虽然NEP - I模拟了病理生理水平ANF的肾脏作用，但NEP - I也增强了在充血性心力衰竭或高血压中观察到的病理生理浓度ANF的利钠作用。
