Webb D J, Manhem P J, Ball S G, Inglis G, Leckie B J, Lever A F, Morton J J, Robertson J I, Murray G D, Ménard J
J Hypertens. 1985 Dec;3(6):653-8. doi: 10.1097/00004872-198512000-00013.
The inhibitor of human renin, H142, was studied in nine male volunteers. On three occasions, in random order, volunteers were infused with 5% dextrose or with H142 at 1.0 or 2.5 mg/kg per h for 30 min while supine and thereafter with dextrose for 1 1/2 h. There was a marked reduction in plasma active renin concentration as assayed by an enzyme-kinetic method, with parallel falls in the circulating concentrations of angiotensins (ANG) I and II, all of which rebounded transiently to values above basal after the H142 infusion was stopped. In contrast, total renin concentration as measured by radio-immunoassay rose while ANG I and II fell, subsiding when H142 was discontinued. There was a slight but significant increase in plasma noradrenaline as renin became inhibited; plasma adrenaline was unchanged. H142 produced a slight fall in systolic blood pressure (SBP) and a clearer, highly significant, dose-related fall in diastolic blood pressure (DBP). There was a modest but significant increase in the heart rate. These studies confirm H142 as an effective inhibitor of human renin in vivo.
在9名男性志愿者身上对人肾素抑制剂H142进行了研究。志愿者按随机顺序接受3次输注，分别为输注5%葡萄糖，或以1.0或2.5毫克/千克每小时的剂量输注H142，每种情况持续30分钟，输注时志愿者为仰卧位，之后再输注1个半小时葡萄糖。采用酶动力学方法测定发现，血浆活性肾素浓度显著降低，同时循环中的血管紧张素（ANG）I和II浓度也随之下降，在停止输注H142后，所有这些指标均短暂反弹至高于基础值。相比之下，通过放射免疫测定法测得的总肾素浓度在ANG I和II下降时升高，在停止使用H142后回落。随着肾素受到抑制，血浆去甲肾上腺素略有但显著升高；血浆肾上腺素则无变化。H142使收缩压（SBP）略有下降，使舒张压（DBP）出现更明显、高度显著的剂量相关下降。心率有适度但显著的增加。这些研究证实H142在体内是人肾素的有效抑制剂。
