ANP infusion in the treatment of heart failure and comparison with ACE inhibition

Abstract

The therapeutic potential of atrial natriuretic peptide (ANP) was assessed in an ovine model of heart failure induced by rapid left ventricular (LV) pacing and compared with the effects of angiotensin converting enzyme (ACE) inhibition. Hemodynamic, hormonal, and metabolic measurements were studied during three 5-day periods of LV pacing. No treatment (control) or a continuous ANP infusion (25 ng/kg/min) was given in random order during the first two periods, while ACE inhibitor was always given during the third period. Baseline measurements immediately prior to the start of each pacing phase showed no significant variation. Significant neurohumoral activation and hemodynamic responses were observed in each pacing phase. During ANP infusion, plasma ANP levels were 3-5-fold higher than those observed in the control or ACE inhibition treatment phases. Compared with control, a natriuresis was observed on the first day, whereas glomerular filtration rate (GFR) tended to be maintained during ANP infusion. The rise in left atrial pressure and plasma aldosterone tended to be blunted. When the two treatment phases were compared, the rise in left atrial pressure during LV pacing was less with ACE inhibition, whereas there was a similar reduction in sodium retention after the initial natriuresis with ANP. By contrast, GFR tended to be maintained better during ANP infusion compared to ACE inhibition. These results suggest that ANP, or a similar "enhancing" analogue, may be useful in the treatment of heart failure, especially if administered early in the development of the disorder.