Differing Early Blood Pressure and Renin-Angiotensin System Responses to the First Dose of Angiotensin-Converting Enzyme Inhibitors in Congestive Heart Failure

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Abstract
We previously demonstrated differing blood pressure (BP) responses to the first dose of angiotensin-converting enzyme (ACE) inhibitors in congestive heart failure (CHF). We wished to confirm the disparate responses to the first dose of these agents, study the response to repeated dosing, and explore possible explanations (slow, tight binding, and steric hindrance) for the phenomenon. Forty-eight elderly patients (aged 51-85 years) with stable CHF were studied for 48 hours. Groups (n = 12) received one of the following: (a) perindopril 2 mg orally (p.o.) + placebo intravenously (i.v.) (day 1) and perindopril 2 mg p.o. (day 2); (b) enalapril 2.5 mg p.o. + placebo i.v. (day 1) and enalapril 2.5 mg p.o. (day 2); (c) placebo p.o. + perindopril at 0.167 mg i.v. (day 1) and perindopril 2 mg p.o. (day 2); or (d) placebo p.o. + placebo i.v. (day 1) and placebo p.o. (day 2). Supine BP was measured on day 1. On day 2, BP was recorded by ambulatory BP monitor. Blood samples were taken at baseline and at intervals during the 48-h study period for estimation of neurohumoral parameters. Inhibition of the renin-angiotensin system (RAS) was estimated by plasma ACE inhibition and also by the ratio of angiotensin II (Ang II)/Ang I + Ang II. On day I, enalapril 2.5 mg caused a greater decrease in BP than did placebo response between 6 and 9 h postdose. Perindopril 2 mg produced a profile of BP response similar to that of placebo. Ambulatory BP on day 2 was consistently lower with enalapril as compared with perindopril. Profiles of plasma ACE inhibition were similar with each active therapy. Enalapril therapy produced a greater increase in plasma renin activity (PRA) than did other treatments. There was no temporal dissociation between plasma ACE inhibition and profile of Ang peptides for any treatment. We have confirmed the disparate BP responses to perindopril and enalapril in CHF. We noted no evidence of slow, tight binding or steric hindrance to explain these differences.

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