Effects of elevation of ANP and its deficiency on cardiorenal function

Atrial natriuretic peptide (ANP), encoded by Nppa, is a vasodilatory hormone that promotes salt excretion. Genome-wide association studies identified Nppa as a causative factor of blood pressure development, and in humans, ANP levels were suggested as an indicator of salt sensitivity. This study aimed to provide insights into the effects of ANP on cardiorenal function in salt-sensitive hypertension. To address this question, hypertension was induced in SS(NPPA–/–) (KO of Nppa in the Dahl salt-sensitive [SS] rat background) or SS(WT) (WT Dahl SS) rats by a high-salt (HS) diet challenge (4% NaCl for 21 days). Chronic infusion of ANP in SS(WT) rats attenuated the increase in blood pressure and cardiorenal damage. Overall, the SS(NPPA–/–) strain demonstrated higher blood pressure and intensified cardiac fibrosis (with no changes in ejection fraction) compared with SS(WT) rats. Furthermore, SS(NPPA–/–) rats exhibited kidney hypertrophy and higher glomerular injury scores, reduced diuresis, and lower sodium and chloride excretion than SS(WT) when fed a HS diet. Additionally, the activity of epithelial Na(+) channel (ENaC) was found to be increased in the collecting ducts of the SS(NPPA–/–) rats. Taken together, these data show promise for the therapeutic benefits of ANP and ANP-increasing drugs for treating salt-sensitive hypertension.