DETERMINANTS OF THE INITIAL EFFECTS OF CAPTOPRIL ON BLOOD-PRESSURE, GLOMERULAR-FILTRATION RATE, AND NATRIURESIS IN MILD-TO-MODERATE CHRONICCONGESTIVE-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. Th e recognized clinical correlates such as hyponatremia and high diureti c dose, which predict occurrence of these adverse effects in severe ch ronic congestive heart failure (CHF), are rarely evident in patients w ith mild-to-moderate CHF. Accordingly, we studied 36 patients with sta ble, moderate CHF in a double-blind, placebo-controlled, crossover fas hion to evaluate by multiple discriminate regression analysis the path ophysiologic determinants of changes in blood pressure, glomerular fil tration rate, and urinary sodium excretion after initial converting en zyme 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 decrea se in plasma norepinephrine (F = 8, p = 0.02), and, inversely by pretr eatment mean arterial pressure (F = 5.6, p = 0.04), patients with high er initial values exhibiting greater decreases in response to captopri l. A captopril-mediated decline in glomerular filtration rate, determi ned 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 pret reatment glomerular filtration rate (F = 11.1, p <0.01), and low absol ute posttreatment serum angiotensin II (F = 5, p = 0.04). Change in ur inary sodium excretion was related directly to change in glomerular fi ltration rate (F = 30.4, p <0.01) and inversely to change in angiotens in 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 chang es in either glomerular filtration rate or urinary sodium excretion. T hese findings emphasize the central role for circulating angiotensin I I in CHF as the modifiable factor that mediates a potent antinatriuret ic action while simultaneously playing a part in maintaining systemic blood pressure and, independently, in maintaining glomerular filtratio n rate.