Valentin J P, Qiu C B, Wiedemann E, Gardner D, Humphreys M H
Division of Nephrology, San Francisco General Hospital, California 94143.
Am J Hypertens. 1992 Feb;5(2):88-91. doi: 10.1093/ajh/5.2.88.
Neutral endopeptidase (EC 3.4.24.11) is a wide-spread enzyme that degrades atrial natriuretic peptide (ANP). We studied the effects of a potent neutral endopeptidase inhibitor, SQ 28,603, given intravenously (30 mg/kg over 45 min) to anesthetized, bilaterally nephrectomized Sprague-Dawley rats. Infusion of vehicle alone was accompanied by a modest increase, 3.2 +/- 2.2% (mean +/- SE), in mean arterial blood pressure (MAP) and a slight rise in hematocrit (Hct) of 0.9 +/- 0.7%. After administration of SQ 28,603, MAP fell 3.2 +/- 0.5%, and Hct rose 4.9 +/- 0.5%, both significantly different from the changes with vehicle alone; the lesser increase in plasma protein concentration (2.5 +/- 0.4%) suggested an increase in vascular permeability to both plasma protein and fluid similar to that caused by ANP. When SQ 28,603 was given to rats pretreated with rabbit antirat ANP antiserum, blood pressure rose by 3.8 +/- 0.5%, and Hct increased by 1.0 +/- 0.4%, values very similar to those observed with vehicle alone. Inhibition of neutral endopeptidase therefore amplifies the actions of endogenous ANP on blood pressure and fluid partition.
中性内肽酶（EC 3.4.24.11）是一种广泛存在的酶，可降解心房利钠肽（ANP）。我们研究了一种强效中性内肽酶抑制剂SQ 28,603对麻醉的、双侧肾切除的Sprague-Dawley大鼠静脉给药（45分钟内给予30 mg/kg）的效果。单独输注赋形剂时，平均动脉血压（MAP）适度升高3.2±2.2%（平均值±标准误），血细胞比容（Hct）略有升高0.9±0.7%。给予SQ 28,603后，MAP下降3.2±0.5%，Hct升高4.9±0.5%，两者均与单独使用赋形剂时的变化有显著差异；血浆蛋白浓度升高幅度较小（2.5±0.4%），提示血管对血浆蛋白和液体的通透性增加，类似于ANP引起的情况。当给用兔抗大鼠ANP抗血清预处理的大鼠给予SQ 28,603时，血压升高3.8±0.5%，Hct升高1.0±0.4%，这些值与单独使用赋形剂时观察到的值非常相似。因此，抑制中性内肽酶可增强内源性ANP对血压和液体分配的作用。
