BETA-BLOCKADE WITH PINDOLOL - DIFFERENTIAL CARDIAC AND RENAL EFFECTS DESPITE SIMILAR PLASMA KINETICS IN NORMAL AND UREMIC MAN

Cardiac and renal effects (measured as the reduction in exercise-induced tachycardia and PRA [plasma renin activity], respectively) and circulating drug concentrations after acute .beta. blockade with i.v. pindolol were compared between 7 normal volunteers and 6 patients with terminal renal failure. Kinetic parameters were similar in both groups (total body clearance, 450 ml/min) indicating enhanced extrarenal elimination in patients. For any given drug concentration, the uremic patients responded to .beta.-blockade with a greater decrease in pulse rate than did normal volunteers (P < 0.001) and the decrease of PRA was more marked (from 13.3 to 5.7 vs. 3.3 to 1.9 ng/ml per h) and lasted longer (8 h and more vs. 2 h). Plasma aldosterone remained unchanged. There is an increased dependency of both heart rate and renin release on .beta.-adrenergic-mediated mechanisms in uremic man. Kinetic findings in normal subjects cannot always be extrapolated to predict kinetic behavior in disease; similar kinetics do not imply similar effectiveness.