The effects of frusemide and angiotensin-converting enzyme inhibitors and their combination on cardiac and renal haemodynamics in heart failure

Few studies exist on the interaction of diuretics and angiotensin-converting enzyme inhibitors in patients with chronic heart failure. Twelve subjects with heart failure were studied before and after their usual oral dose of frusemide in random order on consecutive days during fixed sodium, potassium and water intake. Patients then received 10 mg day-1 of enalapril for 5 days and subsequently restudied before and after their usual dose of frusemide. Frusemide was not observed to have an effect on systemic or renal haemodynamics prior to enalapril, but urine volume and sodium content rose as expected. Treatment with enalapril, in the absence of frusemide, was associated with a fall in mean blood pressure from 89 +/- 5 mmHg to 85 +/- 4 mmHg (P less than 0.02) and a rise in renal blood flow from 424 +/- 202 ml min-1 to 494 +/- 225 ml min-1 (P less than 0.02), but cardiac output and glomerular filtration rate were again unchanged. Addition of frusemide to enalapril therapy resulted in a greater fall in mean blood pressure (87 +/- 5 mmHg to 79 +/- 4 mmHg; P less than 0.01) and an increase in cardiac output (3.1 +/- 1.1 l min-1 to 3.6 +/- 1.0 l min-1; P less than 0.02). Renal blood flow increased further than after enalapril alone to 579 +/- 211 ml min-1, but the glomerular filtration rate fell to 63 +/- 26 ml min-1 (P less than 0.01) and the filtration fraction fell to 19 +/- 5% (P less than 0.001). Weight gain occurred and the diuretic response to frusemide was reduced during this early phase of enalapril therapy.