Hofbauer K G, Wood J M, Gulati N, Heusser C, Ménard J
Hypertension. 1985 May-Jun;7(3 Pt 2):I61-5. doi: 10.1161/01.hyp.7.3_pt_2.i61.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
肾素释放对肾素抑制剂给药的反应无法用用于测量血浆肾素的传统酶法进行研究。在本实验中,一种用于检测人和灵长类肾素的新型多量程酶联免疫吸附测定法被用于研究肾素抑制后血浆免疫反应性肾素的变化。一种强效长效含他汀类肾素抑制剂CGP 29 287,在轻度或重度钠耗竭后注射到清醒的狨猴体内。在轻度钠耗竭的狨猴中,CGP 29 287(静脉注射0.1mg/kg)可降低平均动脉血压,并在长达30分钟内完全抑制血浆肾素活性。这种反应与血浆免疫反应性肾素浓度的短暂升高有关。静脉注射1.0mg/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。这些效应伴随着血浆免疫反应性肾素浓度的持续升高。在严重钠耗竭的狨猴中,CGP 29 287(静脉注射1.0mg/kg)在注射后30分钟内导致收缩压显著下降,并完全抑制血浆肾素活性。血浆免疫反应性肾素水平升至预处理值的257%。转换酶抑制剂依那普利拉(静脉注射2mg/kg)导致收缩压下降幅度相似,同时伴有血浆肾素活性增加。血浆免疫反应性肾素水平升至预处理值的210%。肼屈嗪(静脉注射0.2mg/kg)尽管有类似的降压作用,但并未增加血浆肾素活性或血浆免疫反应性肾素水平。(摘要截短于250字)