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

Abstract

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/1.732 (p < .05), increased the water load excreted in 5 hr from 50% to 71% (p < .005), and increased 5 hr sodium excreted from 6.8 to 14.7 meq (p < .005). Captopril also caused a decrease in plasma norepinephrine from 568 to 448 pg/ml (p < .005), in plasma epinephrine from 94 to 73 pg/ml (p < .05), and in plasma aldosterone from 57 to 28 ng/dl (p< .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 < .05). The long-term response to captopril was similar in patients with higher (> 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 < .05), decreased plasma arginine vasopressin (1.16 to 0.75 pg/ml, p < .05), increased water excretion (62% to 85%, p < .005), and decreased plasma epinephrine (81 to 46 pg/ml, p < .05), while in patients with higher renin levels none of these beneficial effects were noted. We conclude (1) that captopril produces long-term beneficial renal and neurohumoral effects that prazosin does not despite similar hemodynamic changes with the two drugs, (2) that these effects are at least partially dependent on the initial neurohumoral and hemodynamic status of the patient, and (3) that through hemodynamic improvement vasodilators may chronically interrupt vasopressin overstimulation.

Elevated endothelin-1 in heart failure and loss of normal response to postural change.

“…[37][38][39][40] This probably reflects an activation of compensatory mechanisms that are thought to be crucial for the maintenance of circulatory function in heart failure.37 Moreover, there was considerable blunting of response to tilting for each agent in proportion to the degree of basal elevation in plasma levels ( Figure 5). Thus, aldosterone, plasma renin activity, and atrial natriuretic peptide, all markedly elevated in heart failure, showed no significant further change in response to postural stress.…”

Two-year time course and significance of neurohumoral activation in the Survival and Ventricular Enlargement (SAVE) Study

“…Samples which took more than 24 h to reach the central laboratory, or which were haemolyzed or thawed, were not analysed. Previously described neurohormone assays [18,19] were used to measure plasma renin activity and plasma concentrations of norepinephrine, atrial natriuretic peptide, arginine vasopressin, epinephrine, and aldosterone. The pattern of pre-randomization neurohumoral activation and its prognostic significance have been reported previously [2,9] .…”

The Role of Neuroendocrine Abnormalities in the Enhanced Sodium and Water Retention of Chronic Heart Failure

“…Ganglionic blocking drugs and adrenergic antagonists such as phenoxybenzamine improve urinary flow and sodium excretion in CHF (Brod et al 1954;Cannon 1977). It has also recently been shown that the selective al blocker prazosin increases water excretion in patients with CHF, at least in the short term (Mettauer et al 1986). SNS activation also stimulates renin release and enhancement of RAAS activity may also contribute, indirectly, to the role of the SNS in the impaired sodium and water excretion of CHF.…”

“…There is accumulating evidence to suggest that the neurohumoral changes alluded to above have a pivotal role to play. In patients matched for similar degrees of left ventricular dysfunction the severity of renal impairment correlates directly with the overall degree of neuroendocrine derangement (Mettauer et al 1986). This suggests that hormonal changes have an independent primary role in the altered kidney function in CHF.…”