INTERACTIONS OF ATRIAL AND BRAIN NATRIURETIC PEPTIDES AT PATHOPHYSIOLOGICAL LEVELS IN NORMAL MEN

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) a re both circulating plasma hormones that are secreted by the heart and have similar physiological effects. We have shown previously that abr upt increases in plasma BNP in normal humans impair the clearance of A NP from plasma and result in additive physiological effects. Because l arge increases in plasma ANP are reported to have no effect on plasma BNP levels in patients with heart failure, we have studied ANP-BNP int eractions in eight normal male subjects receiving background infusions of BNP (2 pmol . kg(-1). min(-1) for 5 h). Each subject also received a coinfusion of ANP (''active'' day, 2 pmol . kg(-1). min(-1) for 2 h ) or vehicle (''placebo'' day) using a balanced random order, single-b lind design. Metabolic clearance rate of ANP (mean 4.1 +/- 0.6 l/min) and disappearance rate from the plasma (t(1/2) 3.4 +/- 0.3 min) were s imilar to values measured previously in the absence of exogenous BNP. In contrast, steady-state plasma BNP levels were reversibly increased (mean BNP increment 10 pmol/l) during the administration of ANP (P = 0 .038). Associated with these changes were significant (additive) physi ological effects. Thus the addition of ANP increased plasma and urine guanosine 3',5'-cyclic monophosphate (P < 0.001 for both) and lowered systolic blood pressure (P = 0.049). When ANP was coinfused, significa nt differences were also observed in urine volume (P = 0.001) and sodi um excretion (P = 0.043) between the infusion period (when urine volum e and sodium excretion were enhanced) and postinfusion period (when va lues decreased). Taken together, our findings of similar interactions between ANP-BNP and BNP-ANP infusions occurring at pathophysiological concentrations of these two peptides suggest that tile interactions re sult from dissociation of prebound hormone, presumably from biological or clearance receptors.