Sympathoinhibitory effects of atrial natriuretic peptide in rats with heart failure

BACKGROUND: It has been suggested that a blunted sympathoinhibitory response to atrial natriuretic peptide (ANP) may contribute to the elevation of sympathetic activity seen in heart failure. METHODS AND RESULTS: Experiments were performed in anesthetized rats 6 to 9 weeks after coronary ligation to induce heart failure. Responses to intravenous injections of ANP (4 microg/kg) did not differ between the sham-operated (n = 11) and heart-failure (n = 7) rats. Before sinoaortic denervation, ANP decreased mean arterial pressure (MAP) by 8 mm Hg in both the heart-failure and sham rats, renal sympathetic nerve activity (RSNA) by 9% to 10% in both groups, and heart rate (HR) by 12 to 13 beats/min in both groups. After baroreceptor denervation, ANP decreased MAP by approximately 22 mm Hg, RSNA by 14%, and HR by 16 beats/min in both the heart-failure and sham rats. After vagotomy, there was no longer a significant decrease in RSNA or HR in response to ANP. CONCLUSION: The sympathoinhibitory effects of ANP are maintained in heart failure. This suggests that the elevated sympathetic activity observed in heart failure cannot be attributed to a blunting of the response to ANP.