RENAL, ENDOCRINE, AND HEMODYNAMIC-EFFECTS OF HUMAN BRAIN NATRIURETIC PEPTIDE IN NORMAL MAN

Brain Natriuretic Peptide (BNP) is a recently identified hormone which is secreted by the human heart and circulates in plasma. To determine the effects of pathophysiological levels of human BNP (hBNP), we have studied the integrated renal, hormonal, and hemodynamic response in six normal men receiving 2-h infusions of synthetic hBNP (2.0 pmol/kg.min) or placebo in random order. Steady state levels of hBNP (20-30 pmol/L), achieved at 90-120 min, were similar to levels observed in mild heart failure. Compared to placebo infusions, hBNP induced a greater than 2-fold increase in sodium excretion (P = 0.014) and suppressed plasma aldosterone (P < 0.004) to levels less than 50% of placebo values. These changes were associated with an increase in both plasma (P = 0.028) and urine excretion (P < 0.004) of cGMP. Effects on blood pressure were not statistically significant but increases in both heart rate (P < 0.0001) and plasma albumin (P = 0.007) after cessation of hBNP infusions indicate significant hemodynamic effects of hBNP. High MCR (5.8 +/- 0.7 L/min) yet slow disappearance rate (mean t1/2 22.6 min) indicate that hBNP has a large volume of distribution in humans. These studies show that hBNP, at plasma levels observed in patients with mild heart failure, has potentially important natriuretic, endocrine, and hemodynamic effects which are similar to those observed with comparable infusion rates of ANF.