BNP - PATHOPHYSIOLOGICAL AND POTENTIAL THERAPEUTIC ROLES IN ACUTE CONGESTIVE-HEART-FAILURE

Controversy persists regarding the acute responsiveness of atrial (ANP ) and brain (BNP) natriuretic peptides in pathophysiological condition s such as acute heart failure (AHF). This study was designed to test t he hypothesis that AHF is characterized by selective activation of ANP , but not BNP. We also hypothesized that BNP replacement in AHF would reduce cardiac filling pressures, increase sodium excretion, and inhib it circulating renin. Two groups of anesthetized dogs underwent rapid left ventricular pacing to induce AHF. Group 1 (n = 7) served as contr ol and group 2 (n = 7) received canine BNP (10 ng.kg(-1).min(-1)). Car diorenal parameters, circulating natriuretic peptides, 3',5'-cyclic gu anosine monophosphate (cGMP), and plasma renin activity (PRA) were det ermined at baseline and during AHF in both groups. AHF was characteriz ed by reductions in cardiac output (2.3 +/- 0.2 vs. 3.7 +/- 0.3 l/min, P < 0.05), pulmonary capillary wedge pressure (PCWP; 11.7 +/- 0.8 vs. 5.1 +/- 0.3 mmHg, P < 0.05), and selective activation of ANP (250 +/- 51 vs. 39 +/- 13 pg/ml, P < 0.05), with no increase in circulating BN P (49 +/- 15 vs. 50 +/- 16 pg/ml, P = not significant). Compared with control, exogenous supplemental BNP in AHF resulted in marked increase s in circulating cGMP (65 +/- 6 vs. 18 +/- 5 pg/ml, P < 0.05), with re ductions in PCWP (9.1 +/- 0.9 vs. 12.9 +/- 1.1 mmHg, P < 0.05) and inc reased urinary sodium excretion (120 +/- 36.8 vs. 24 +/- 6.3 mu eq/min , P < 0.05) via reductions in distal tubular sodium reabsorption (94.3 +/- 1.8 vs. 98.0 +/- 0.4%, P < 0.05). Exogenous BNP prevented the inc rease in PRA that occurred in the control group. We conclude that AHF is characterized by a failure to increase circulating BNP underscoring differential physiological and pathophysiological roles for ANP and B NP in states of immediate cardiac overload. These studies also support a potential role for BNP in the therapeutics of AHF.