TY - JOUR
T1 - Effects of elevation of ANP and its deficiency on cardiorenal function
AU - Ilatovskaya, Daria V.
AU - Levchenko, Vladislav
AU - Winsor, Kristen
AU - Blass, Gregory R.
AU - Spires, Denisha R.
AU - Sarsenova, Elizaveta
AU - Polina, Iuliia
AU - Zietara, Adrian
AU - Paterson, Mark
AU - Kriegel, Alison J.
AU - Staruschenko, Alexander
N1 - Funding Information:
We are grateful to Andrey Ilatovskiy for developing the software used to schedule GFR experiments; Histology Core at the Medical College of Wisconsin for their help with the histological needs; and Attoquant Diagnostics GmbH for RAAS panel analysis. The study was supported by the NIH grants R35 HL135749 (AS), P01 HL116264 (AS), R01 HL148114 (DVI), American Heart Association Postdoctoral Fellowship no. 903584 (DRS), Department of Veteran Affairs I01 BX004024 (AS), and the American Physiological Society Lazaro J Mandel award (DVI).
Publisher Copyright:
© 2022, Ilatovskaya et al.
PY - 2022/5/9
Y1 - 2022/5/9
N2 - 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.
AB - 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.
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U2 - 10.1172/jci.insight.148682
DO - 10.1172/jci.insight.148682
M3 - Article
C2 - 35380994
AN - SCOPUS:85129984120
SN - 2379-3708
VL - 7
JO - JCI Insight
JF - JCI Insight
IS - 9
M1 - e148682
ER -