THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM AND FRUSEMIDE RESPONSE IN CONGESTIVE-HEART-FAILURE

1 To test the hypothesis that basal renin angiotensin aldosterone syst em (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 N ew York Heart Association Class II or III CHF, and echocardiographic e vidence of left ventricular dysfunction due to myocardial infarction, hypertension, or both causes. 2 All patients received three dosing reg imens administered in random order:(a) intravenous frusemide: 40 mg bo lus then 40 mg h(-1) for 3 h, (b) captopril: two 12.5 mg oral doses se parated 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) s odium diet was documented prior to each dosing regimen. Sodium excreti on was quantitated in urine collected at intervals until 3.5 h after i nitiating drug administration. During this time, urine output was repl aced intravenously with an equivalent volume of 0.45% saline. 3 Captop ril significantly lowered plasma angiotensin converting enzyme (ACE) a ctivity and plasma aldosterone concentration, and raised inulin cleara nce. The drug had essentially no effect on the time course or magnitud e of frusemide's natriuretic effect. Maximal fractional sodium excreti on during frusemide infused by itself and in combination with captopri l was 24.7 +/- 1.9% vs 28.2 +/- 3.8%, respectively (difference 3.5%; 9 5% 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). Captopril alone produced minimal changes in sodium e xcretion. The ACE inhibitor did not significantly alter urinary frusem ide excretion, p-aminohippurate clearance, blood pressure or cardiac o utput. 4 In patients with compensated mild or moderate CHF, captopril does not acutely affect the delivery of frusemide to its active site o r the ensuing natriuresis. Thus, it does not appear that basal RAAS ac tivity significantly modulates acute diuretic response in this subset of CHF patients.