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Fifty patients with congestive heart failure received, by infusion, 15 ml/kg body weight water load, and systemic hemodynamic, renal function, and neurohumoral parameters values were measured before, 2 days, and 1 month after randomly allocating patients to prazosin or captopril therapy. Both prazosin and captopril caused similar and persistent hemodynamic changes, but important differences existed between their renal and neurohumoral effects. After 1 month of continuous therapy, captopril increased creatinine clearance from 71 to 84 ml/min/1.73(2) (p less than .05), increased the water load excreted in 5 hr from 50% to 71% (p less than .005), and increased 5 hr sodium excreted from 6.8 to 14.7 meq (p less than .005), Captopril also caused a decrease in plasma norepinephrine from 568 to 448 pg/ml (p less than .005), in plasma epinephrine from 94 to 73 pg/ml (p less than .05), and in plasma aldosterone from 57 to 28 ng/dl (p less than .005), without changing plasma vasopressin. These beneficial effects were greater after 1 month of therapy than after 2 days. The only beneficial effect of prazosin was to increase water excretion from 49% to 59% (p less than .05). The long-term response to captopril was similar in patients with higher (greater than 2.5 ng/ml/hr) and lower renin levels. However, in patients with lower renin levels, prazosin decreased pulmonary capillary wedge pressure (24.8 to 21.8 mm Hg, p less than .05), decreased plasma arginine vasopressin (1.16 to 0.75 pg/ml, p less than .05), increased water excretion (62% to 85%, p less than .005), and decreased plasma epinephrine (81 to 46 pg/ml, p less than .05), while in patients with higher renin levels none of these beneficial effects were noted. We conclude that captopril produces long-term beneficial renal and neurohumoral effects that prazosin does not despite similar hemodynamic changes with the two drugs, that these effects are at least partially dependent on the initial neurohumoral and hemodynamic status of the patient, and that through hemodynamic improvement vasodilators may chronically interrupt vasopressin overstimulation.

circulation

Differential long-term intrarenal and neurohormonal effects of captopril and prazosin in patients with chronic congestive heart failure: importance of initial plasma renin activity.