Effects of elevation of ANP and its deficiency on cardiorenal function
Daria V. Ilatovskaya, Vladislav Levchenko, Kristen Winsor, Gregory R. Blass, Denisha R. Spires, Elizaveta Sarsenova, Iuliia Polina, Adrian Zietara, Mark Paterson, Alison J. Kriegel, Alexander Staruschenko
Daria V. Ilatovskaya, Vladislav Levchenko, Kristen Winsor, Gregory R. Blass, Denisha R. Spires, Elizaveta Sarsenova, Iuliia Polina, Adrian Zietara, Mark Paterson, Alison J. Kriegel, Alexander Staruschenko
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Research Article Nephrology

Effects of elevation of ANP and its deficiency on cardiorenal function

Abstract

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 SSNPPA–/– (KO of Nppa in the Dahl salt-sensitive [SS] rat background) or SSWT (WT Dahl SS) rats by a high-salt (HS) diet challenge (4% NaCl for 21 days). Chronic infusion of ANP in SSWT rats attenuated the increase in blood pressure and cardiorenal damage. Overall, the SSNPPA–/– strain demonstrated higher blood pressure and intensified cardiac fibrosis (with no changes in ejection fraction) compared with SSWT rats. Furthermore, SSNPPA–/– rats exhibited kidney hypertrophy and higher glomerular injury scores, reduced diuresis, and lower sodium and chloride excretion than SSWT when fed a HS diet. Additionally, the activity of epithelial Na+ channel (ENaC) was found to be increased in the collecting ducts of the SSNPPA–/– rats. Taken together, these data show promise for the therapeutic benefits of ANP and ANP-increasing drugs for treating salt-sensitive hypertension.

Authors

Daria V. Ilatovskaya, Vladislav Levchenko, Kristen Winsor, Gregory R. Blass, Denisha R. Spires, Elizaveta Sarsenova, Iuliia Polina, Adrian Zietara, Mark Paterson, Alison J. Kriegel, Alexander Staruschenko

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Figure 1

Both the therapeutic and preventive chronic infusion of ANP lower mean arterial pressure in male SSWT rats.

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Both the therapeutic and preventive chronic infusion of ANP lower mean a...
(A) The experimental protocol for the “preventive” infusion of ANP to the SSWT rats; yellow arrows denote metabolic cage urine collections. (B) The mean arterial pressure (MAP) following i.v. infusion of 100 ng/kg/day ANP (n = 8) or vehicle (saline, n = 9) performed together with the 21-day HS diet challenge; P < 0.01 in HS diet–fed groups (vehicle versus infusion) starting day 1 of the infusion. (C) The experimental protocol for the “therapeutic” infusion of ANP to the SSWT rats; yellow arrows denote metabolic cage urine collections. (D) I.v. infusion of 100 ng/kg/day ANP (n = 7) or vehicle (saline, n = 5) was started on day 14 of the 21-day HS diet challenge. P < 0.01 in HS diet–fed groups (vehicle versus infusion) starting day 1 of the infusion. (E and F) Graphs summarize 2 kidneys/body weight and heart/body weight ratios obtained at the end of the protocols. n = 14, 8, and 7 individual rats. Groups are the following: vehicle, rats infused with ANP for the last 7 days of the HS challenge (14–21 days), and throughout the HS challenge (0–21 days). (G) Plasma levels of ANP in the SSWT rats fed a NS and a HS diet, and administered with 100 ng/kg/day ANP for 21 days during a HS challenge (HS and ANP, 0–21 days). Data were analyzed with 1-way ANOVA followed by a Holm-Sidak post hoc test; significant P values are shown on the graphs. Male animals were used.