DETERMINANTS OF THE INITIAL EFFECTS OF CAPTOPRIL ON BLOOD-PRESSURE, GLOMERULAR-FILTRATION RATE, AND NATRIURESIS IN MILD-TO-MODERATE CHRONIC CONGESTIVE-HEART-FAILURE SECONDARY TO CORONARY-ARTERY DISEASE

Whereas angiotensin-converting enzyme inhibitors are now indicated for all grades of chronic heart failure, the 2 adverse effects that limit use of these drugs are systemic hypotension and renal dysfunction. The recognized clinical correlates such as hyponatremia and high diuretic dose, which predict occurrence of these adverse effects in severe chronic congestive heart failure (CHF), are rarely evident in patients with mild-to-moderate CHF. Accordingly, we studied 36 patients with stable, moderate CHF in a double-blind, placebo-controlled, crossover fashion to evaluate by multiple discriminate regression analysis the pathophysiologic determinants of changes in blood pressure, glomerular filtration rate, and urinary sodium excretion after initial converting enzyme inhibition with captopril 25 mg. A captopril-mediated decrease in mean arterial pressure was predicted by 3 factors (r(2) = 0.74): the decrease in serum angiotensin II (F ratio = 10.3, p <0.01), the decrease in plasma norepinephrine (F = 8, p = 0.02), and, inversely by pretreatment mean arterial pressure (F = 5.6, p = 0.04), patients with higher initial values exhibiting greater decreases in response to captopril. A captopril-mediated decline in glomerular filtration rate, determined by radioisotope elimination, was also predicted by 3 factors (r(2) = 0.67): a decrease in renal plasma now (F = 48.6, p <0.01), low pretreatment glomerular filtration rate (F = 11.1, p <0.01), and low absolute posttreatment serum angiotensin II (F = 5, p = 0.04). Change in urinary sodium excretion was related directly to change in glomerular filtration rate (F = 30.4, p <0.01) and inversely to change in angiotensin II level (F = 4.7, p = 0.05) in response to captopril (r(2) = 0.73). Captopril-mediated effects on blood pressure did not determine changes in either glomerular filtration rate or urinary sodium excretion. These findings emphasize the central role for circulating angiotensin II in CHF as the modifiable factor that mediates a potent antinatriuretic action while simultaneously playing a part in maintaining systemic blood pressure and, independently, in maintaining glomerular filtration rate.