Renal, endocrine, and hemodynamic interactions of atrial and brain natriuretic peptides in normal men

Brain natriuretic peptide (BNP) is a recently identified hormone that is secreted by the human heart and circulates in plasma with natriuretic, endocrine, and hemodynamic effects similar to those of atrial natriuretic peptide (ANP). To examine the interaction of human BNP with ANP, we studied eight normal men receiving constant infusions of ANP (2.0 pmol.kg-1.min-1 for 5 h), with and without superimposed infusions of BNP (2.0 pmol.kg-1.min-1 for 2 h), using a balanced random-order design. BNP infusions achieved plasma levels of 30-35 pmol/l at 90-120 min and were similar to levels observed in mild heart failure. Metabolic clearance rate of BNP (mean 4.6 +/- 0.4 l/min) and disappearance rate from plasma (t1/2 18.9 min) were similar to values determined previously in the absence of exogenous ANP. In contrast, the addition of BNP induced a progressive and reversible increase (50%) in steady-state plasma ANP. Compared with ANP alone, BNP induced an additional (50%) increase in sodium excretion (P < 0.05) and significant increases in both plasma (P < 0.001) and urine guanosine 3',5'-cyclic monophosphate (P < 0.01). Systolic blood pressure was lowered by the addition of BNP (P < 0.01) and continued to fall after cessation of BNP infusions. Despite this, the response of the renin-aldosterone and sympathetic nervous systems (heart rate and plasma catecholamines) was not significantly different on the two study days. As well as showing additive effects of the two natriuretic peptides, these studies point to important interactions of BNP on ANP metabolism at plasma levels observed in mild heart failure.