Inhibition of ANP clearance receptors and endopeptidase 24.11 in maturing rats.
Inhibition of ANP clearance receptors and endopeptidase 24.11 in maturing rats.
复制标题
成熟大鼠中 ANP 清除受体和内肽酶 24.11 的抑制。
DOI：
10.1152/ajpregu.1991.260.6.r1218
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Carey,RM
中科院分区：
文献类型：
--
作者：
Chevalier,RL;Garmey,M;Scarborough,RM;Linden,J;Gomez,RA;Peach,MJ;Carey,RM
在出生后的发育过程中，心房利钠肽（ANP）的全身清除率降低。为了确定ANP清除(C)受体和中性内肽酶24.11 （NEP; EC 3.4.24.11）在成熟过程中调节血浆ANP浓度（[ANP]）中的相对作用，将18 ~ 60日龄雄性sd大鼠麻醉并注入大鼠ANP （35 ng.kg-1.min-1）。在断奶和成年大鼠中，输注NEP抑制剂磷酰胺增加了[ANP]和尿中鸟苷3',5'-环单磷酸（cGMP）的排泄。C-ANP是一种选择性结合C受体的类似物，输注C-ANP导致断奶前大鼠的[ANP]高于成年大鼠，这表明C受体功能的成熟下降。然而，尽管[ANP]增加，与成年大鼠相比，断奶前大鼠的尿流量、cGMP和钠排泄并未增加。磷酰胺和C-ANP联合输注可显著增加断奶大鼠和成年大鼠[ANP]和cGMP的排泄量。这些结果表明，C受体和NEP都在生理范围内调节血浆[ANP]，当另一种途径被抑制时，两种途径相互补偿。肾脏对ANP清除抑制剂反应的年龄相关差异可能对发育过程中钠平衡的调节具有重要的生理意义。
Systemic clearance of atrial natriuretic peptide (ANP) decreases during postnatal development. To determine the relative contribution of ANP clearance (C) receptors and neutral endopeptidase 24.11 (NEP; EC 3.4.24.11) in regulation of plasma ANP concentration ([ANP]) during maturation, 18- to 60-day-old male Sprague-Dawley rats were anesthetized and infused with rat ANP (35 ng.kg-1.min-1). Infusion of the NEP inhibitor phosphoramidon increased [ANP] and urine guanosine 3',5'-cyclic monophosphate (cGMP) excretion in both weanling and adult rats. Infusion of C-ANP, an analogue that binds C receptors selectively, resulted in a greater rise in [ANP] in preweaned than in adult rats, suggesting a maturational decrease in function of C receptors. Despite the increase in [ANP], however, urine flow, cGMP, and sodium excretion failed to increase in preweaned compared with adult rats. Combined infusion of phosphoramidon and C-ANP resulted in a marked increase in [ANP] and cGMP excretion in weanling and adult rats. These results indicate that both C receptors and NEP modulate plasma [ANP] in the physiological range and that each pathway compensates when the other is inhibited. Age-related differences in the renal response to ANP clearance inhibitors may have important physiological implications in the regulation of sodium balance during development.