MacFadyen R J, Elliott H L, Meredith P A, Reid J L
University Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary, Glasgow.
Br J Clin Pharmacol. 1993 Mar;35(3):299-301. doi: 10.1111/j.1365-2125.1993.tb05697.x.
A combination of dietary sodium restriction (40 mmol day-1) and frusemide pretreatment has been used to activate the renin angiotensin system (RAS) in order to characterise the haemodynamic and hormonal responses to enalapril in young normotensives. Enalapril significantly reduced supine blood pressure with a mean maximum fall of 19 +/- 7.6, compared with 6.5 +/- 6.8 mm Hg with placebo. Similar but greater responses were seen in erect blood pressure. Mean maximal plasma ACE inhibition (78 +/- 5.7%) was associated with a significant increase in PRA from 5.2 +/- 2.1 ngAI ml-1 h-1 to a peak of 29.1 +/- 6 ngAI ml-1 h-1. This simple well tolerated regimen produced consistent RAS activation and gave readily measurable falls in blood pressure following enalapril. This model may be used to undertake detailed assessments of ACE inhibition, renin inhibition and angiotensin receptor blockade.
采用饮食限钠(40 mmol/天)与速尿预处理相结合的方法激活肾素血管紧张素系统(RAS),以研究年轻血压正常者对依那普利的血流动力学和激素反应。与安慰剂组平均最大血压下降6.5±6.8 mmHg相比,依那普利显著降低仰卧位血压,平均最大降幅为19±7.6 mmHg。立位血压出现类似但更大的反应。平均最大血浆ACE抑制率为(78±5.7%),同时PRA从5.2±2.1 ngAI/ml·h-1显著升高至峰值29.1±6 ngAI/ml·h-1。这种简单且耐受性良好的方案可产生持续的RAS激活,并使依那普利给药后血压出现易于测量的下降。该模型可用于对ACE抑制、肾素抑制和血管紧张素受体阻断进行详细评估。