The renin angiotensin aldosterone system and frusemide response in congestive heart failure

1. To test the hypothesis that basal renin angiotensin aldosterone system (RAAS) activity impairs the acute natriuretic response to frusemide in patients with mild or moderate congestive heart failure (CHF), we studied eight adult volunteers with preserved renal function, stable New York Heart Association Class II or III CHF, and echocardiographic evidence of left ventricular dysfunction due to myocardial infarction, hypertension, or both causes. 2. All patients received three dosing regimens administered in random order: (a) intravenous frusemide: 40 mg bolus then 40 mg h‐1 for 3 h, (b) captopril: two 12.5 mg oral doses separated by 2 h, (c) combined dosing: the first captopril dose preceded the frusemide bolus by 30 min. Sodium balance on an 80 mmol day‐1 sodium diet was documented prior to each dosing regimen. Sodium excretion was quantitated in urine collected at intervals until 3.5 h after initiating drug administration. During this time, urine output was replaced intravenously with an equivalent volume of 0.45% saline. 3. Captopril significantly lowered plasma angiotensin converting enzyme (ACE) activity and plasma aldosterone concentration, and raised inulin clearance. The drug had essentially no effect on the time course of magnitude of frusemide's natriuretic effect. Maximal fractional sodium excretion during frusemide infused by itself and in combination with captopril was 24.7 +/‐ 1.9% vs 28.2 +/‐ 3.8%, respectively (difference 3.5%; 95% CI, ‐4.0 to 11.0%; P > 0.05). Cumulative sodium excretion ending at 3.5 h was 429 +/‐ 53 mmol when frusemide was given alone and 455 +/‐ 69 mmol when captopril was added (difference, 26 mmol; CI, ‐121 to 174 mmol; P > 0.05).