Renal role of the endogenous natriuretic peptide system in acute congestive heart failure

Background: Atrial and brain natriuretic peptides exert renal and cardiovascular actions through binding to the natriuretic peptide-A receptor, while C-type natriuretic peptide mediates actions that occur through binding to the natriuretic peptide-B receptor, with subsequent generation of cyclic guanosine monophosphate. This study determined responses of circulating atrial natriuretic peptides in experimental acute heart failure and addressed the hypothesis that elevated circulating atrial natriuretic peptides serve a homeostatic role in regulating sodium excretion and that this action is localized to the glomerulus and distal nephron, sites rich in natriuretic peptide-A receptors. Methods and Results: Studies were performed in the absence and presence of HS-142-1, an inhibitor of the natriuretic peptide receptors. Two groups of anesthetized dogs underwent induction of acute heart failure by rapid ventricular pacing, as characterized by decreases in cardiac output and increases in filling pressures with associated elevation of endogenous atrial natriuretic peptides secondary to increases in atrial stretch. In group 1 (n = 5, vehicle intrarenal bolus), despite acute heart failure-mediated decreases in cardiac output, sodium excretion was preserved with maintenance of the glomerular filtration rate and distal fractional sodium reabsorption. In group 2 (n = 5), in response to the natriuretic peptide receptor antagonist, HS-142-1 (0.5 mg/kg intrarenal bolus), sodium excretion (17.0 ± 4.4 to 5.9 ± 3.2 μEq/min; P < .05) and glomerular filtration rate decreased (33.0 ± 3.6 to 21.0 ± 3.9 mL/min; P < .05) and distal fractional sodium reabsorption increased (98.0 ± 0.63 to 99.3 ± 0.25%; P < .05), in association with a decrease in plasma cyclic guanosine monophosphate (13.0 ± 3.5 to 6.6 ± 2.9 pmol/mL; P < .05) and renal cyclic guanosine monophosphate generation (1,216 ± 421 to 466 ± 208 pmol/min; P < .05). Conclusions: This study supports a functionally significant role for the endogenous natriuretic peptide system in preserving sodium homeostasis and glomerular filtration rate in acute heart failure.