Increased Plasma Renin During Renin Inhibition: Studies with a Novel Immunoassay
Increased Plasma Renin During Renin Inhibition: Studies with a Novel Immunoassay
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肾素抑制期间血浆肾素增加：采用新型免疫测定法的研究
作者：
K. Hofbauer;J. Wood;N. Gulati;C. Heusser
不能用测量血浆肾素的常规酶法研究肾素释放对给予肾素抑制剂的反应。在本实验中，一种新的多范围酶联免疫吸附测定人和灵长类动物的肾素被用来研究血浆中的免疫反应性肾素抑制后的变化。一种有效的和长效的含他汀类药物的肾素抑制剂，CGP 29 287，注射在清醒的绒猴后，轻度或严重的钠耗竭。在轻度钠缺乏的绒猴中，CGP 29 287（0.1 mg/kg i. v.）降低平均动脉血压并完全抑制血浆肾素活性长达30分钟。这种反应与血浆免疫反应性凝乳酶浓度的短暂增加有关。静脉注射1.0 mg/kg剂量后，平均动脉压的降低和血浆肾素活性的完全抑制持续长达120分钟。这些影响伴随着血浆免疫反应性肾素浓度的持续增加。在严重钠缺乏的绒猴中，CGP 29 287（1.0 mg/kg i. v.）在注射后30分钟内诱导收缩压显著下降，并完全抑制血浆肾素活性。血浆免疫反应性肾素水平增加到治疗前值的257%。转化酶抑制剂依那普利拉（2 mg/kg静脉注射）引起收缩压下降相似的幅度，这是伴随着血浆肾素活性的增加。血浆免疫反应性肾素水平增加到治疗前值的210%。肼苯哒嗪（0.2 mg/kg i. v.）不增加血浆肾素活性或血浆免疫反应性肾素水平，尽管有相当的消肿作用。这些结果表明，抑制肾素或转换酶诱导类似的增加，可能是由一个共同的机制介导的肾素释放-撤销负反馈抑制循环血管紧张素II。
The response of renin release to the administration of renin inhibitors cannot be studied with conventional enzymatic methods used to measure plasma renin. In the present experiments, a novel multirange enzyme-linked immunosorbent assay for human and primate renin was used to investigate the changes in plasma immunoreactive renin after renin inhibition. A potent and long-acting statine-containing renin inhibitor, CGP 29 287, was injected in conscious marmosets after mild or severe sodium depletion. In mildly sodium-depleted marmosets, CGP 29 287 (0.1 mg/kg i.v.) reduced mean arterial blood pressure and completely inhibited plasma renin activity for up to 30 minutes. This response was associated with a transient increase in plasma immunoreactive renin concentration. After a dose of 1.0 mg/kg i.v., the reduction of mean arterial pressure and the complete inhibition of plasma renin activity persisted for up to 120 minutes. These effects were accompanied by a sustained increase in plasma immunoreactive renin concentration. In severely sodium-depleted marmosets, CGP 29 287 (1.0 mg/kg i.v.) induced a marked fall in systolic blood pressure and complete inhibition of plasma renin activity within 30 minutes of injection. Plasma immunoreactive renin levels increased to 257% of pretreatment values. The converting-enzyme inhibitor enalaprilat (2 mg/kg i.v.) induced a fall in systolic blood pressure of similar magnitude, which was accompanied by an increase in plasma renin activity. Levels of plasma immunoreactive renin increased to 210% of pretreatment values. Hydralazine (0.2 mg/kg i.v.) did not increase plasma renin activity or plasma immunoreactive renin levels despite a comparable hypotensive effect. These results indicate that inhibition of renin or converting enzyme induces a similar increase in renin release that probably is mediated by a common mechanism — the withdrawal of the negative feedback suppression by circulating angiotensin II.