Divergent effects of ANP and BNP in acute heart failure: evidence for a putative BNP-selective receptor?

OBJECTIVE

Since the pathophysiology of natriuretic peptides in chronic heart failure (HF) is not uniform, we hypothesized that atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) may also have differential effects in acute HF. Our aim was to compare the haemodynamic actions of ANP with BNP, using a classical vasodilator as the control, in greyhound dogs with acute pacing-induced HF.

DESIGN AND METHODS

The right ventricles of eight anaesthetized dogs were paced (193 +/- 4 bpm) until pulmonary capillary pressure (PCP) increased to approximately 15 mmHg. In each animal, according to a randomized within-animal design, haemodynamic responses to equimolar (10 pmol/kg per min) infusions of ANP and BNP were compared with those to sodium nitroprusside (SNP).

RESULTS

Acute pacing alone increased PCP from 6.6 +/- 0.7 to 15.7 +/- 0.3 mmHg, right atrial pressure (RAP) from 1.9 +/- 0.5 to 4.0 +/- 0.6 mmHg, and systemic vascular resistance (SVR) from 1706 +/- 110 to 2179 +/- 106 dyne s/cm5, and reduced cardiac output (CO) from 4.1 +/- 0.4 to 2.5 +/- 0.2 l/min and arterial pressure from 86.1 +/- 2.4 to 74.5 +/- 2.1 mmHg (all P < 0.01). BNP and SNP improved haemodynamics similarly (CO +13 +/- 3% and +9 +/- 5%; PCP -12 +/- 2% and -12 +/- 2%; RAP -28 +/- 9% and -34 +/- 6%, SVR -15 +/- 3% and -11 +/- 3%, all P < 0.01, except CO with SNP, not significant), but effects of BNP on preload outlasted those of SNP. By contrast, ANP did not improve the haemodynamics. Haematocrit was significantly higher during BNP infusion than with ANP (P < 0.05) or with SNP (P < 0.001).

CONCLUSIONS

The haemodynamic responses to exogenous BNP and ANP in acute heart failure were strikingly different. Whereas ANP actions were blunted, BNP response was preserved. Hypothetically, the presence of a putative BNP receptor may explain this finding.