Controversy persists regarding the acute responsiveness of atrial (ANP) and brain (BNP) natriuretic peptides in pathophysiological conditions such as acute heart failure (AHF). This study was designed to test the 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 inhibit circulating renin. Two groups of anesthetized dogs underwent rapid left ventricular pacing to induce AHF. Group 1 (n = 7) served as control and group 2 (n = 7) received canine BNP (10 ng · kg-1 · min-1). Cardiorenal parameters, circulating natriuretic peptides, 3',5'-cyclic guanosine monophosphate (cGMP), and plasma renin activity (PRA) were determined at baseline and during AHF in both groups. AHF was characterized 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 BNP (49 ± 15 vs. 50 ± 16 pg/ml, P = not significant). Compared with control, exogenous supplemental BNP in AHF resulted in marked increases in circulating cGMP (65 ± 6 vs. 18 ± 5 pg/ml, P < 0.05), with reductions in PCWP (9.1 ± 0.9 vs. 12.9 ± 1.1 mmHg, P < 0.05) and increased urinary sodium excretion (120 ± 36.8 vs. 24 ± 6.3 μeq/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 increase 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 BNP in states of immediate cardiac overload. These studies also support a potential role for BNP in the therapeutics of AHF.
|Original language||English (US)|
|Journal||American Journal of Physiology - Regulatory Integrative and Comparative Physiology|
|Issue number||4 41-4|
|State||Published - 1997|
- natriuretic peptide system
- sodium excretion
ASJC Scopus subject areas