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 natriuret ic, endocrine, and hemodynamic effects similar to those of atrial natr iuretic peptide (ANP). To examine the interaction of human BNP with AN P, we studied eight normal men receiving constant infusions of ANP (2. 0 pmol.kg(-1).min(-1) for 5 h), with and without superimposed infusion s of BNP (2.0 pmol. kg(-1).min(-1) for 2 h), using a balanced random-o rder design. BNP infusions achieved plasma levels of 30-35 pmol/l at 9 0-120 min and were similar to levels observed in mild heart failure. M etabolic clearance rate of BNP (mean 4.6 +/- 0.4 l/min) and disappeara nce rate from plasma (t(1/2) 18.9 min) were similar to values determin ed previously in the absence of exogenous ANP. In contrast, the additi on of BNP induced a progressive and reversible increase (50%) in stead y-state plasma ANP. Compared with ANP alone, BNP induced an additional (50%) increase in sodium excretion (P < 0.05) and significant increas es in both plasma (P < 0.001) and urine guanosine 3',5'-cyclic monopho sphate (P < 0.01). Systolic blood pressure was lowered by the addition of BNP (P < 0.01) and continued to fall after cessation of BNP infusi ons. Despite this, the response of the renin-aldosterone and sympathet ic nervous systems (heart rate and plasma catecholamines) was not sign ificantly different on the two study days. As well as showing additive effects of the two natriuretic peptides, these studies point to impor tant interactions of BNP on ANP metabolism at plasma levels observed i n mild heart failure.