The effects of the atrial natriuretic peptide deficiency on renal cortical mitochondrial bioenergetics in the Dahl SS rat

Atrial Natriuretic Peptide (ANP) plays an important role in blood pressure regulation. Low levels of ANP correlate with the development of salt‐sensitive hypertension (SS‐HTN). Our previous studies indicated that ANP deficiency exacerbated renal function decline in SS‐HTN. In the heart and fat tissu...

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Published in:	The FASEB journal Vol. 38; no. 16; pp. e23891 - n/a
Main Authors:	Cherezova, Alena, Sudarikova, Anastasia, Vasileva, Valeriia, Iurchenko, Regina, Nikiforova, Anna, Spires, Denisha R., Zamaro, Aleksandra S., Jones, Adam C., Schibalski, Ryan S., Dong, Zheng, Palygin, Oleg, Stadler, Krisztian, Ilatovskaya, Daria V.
Format:	Journal Article
Language:	English
Published:	United States 31-08-2024
Subjects:	Animals Atrial Natriuretic Factor - metabolism Energy Metabolism Hypertension - etiology Hypertension - metabolism Hypertension - pathology Kidney Cortex - metabolism Kidney Cortex - pathology Male Mitochondria - metabolism Oxidative Stress Rats Rats, Inbred Dahl Sodium Chloride, Dietary - adverse effects
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Summary:	Atrial Natriuretic Peptide (ANP) plays an important role in blood pressure regulation. Low levels of ANP correlate with the development of salt‐sensitive hypertension (SS‐HTN). Our previous studies indicated that ANP deficiency exacerbated renal function decline in SS‐HTN. In the heart and fat tissue, ANP was reported to affect lipid peroxidation and mitochondrial bioenergetics but the effects of ANP on mitochondrial function in the kidney are unexplored. We hypothesized that ANP deficiency in SS‐HTN causes renal bioenergetic shift, leading to disruption of mitochondrial network and oxidative stress. To address the hypothesis, we placed Dahl SS wild‐type (SSWT) and ANP knockout (SSNPPA−/−) rats on 4% NaCl high salt (HS) diet to induce HTN or maintained them on 0.4% NaCl normal salt (NS) diet and assessed mitochondrial bioenergetics and dynamics using spectrofluorimetry, Seahorse assay, electron paramagnetic resonance (EPR) spectroscopy, Western blotting, electron microscopy, PCR and cytokine assays. We report that under high salt conditions, associated with hypertension and renal damage, the SSNPPA−/− rats exhibit a decrease in mitochondrial membrane potential and elevation in mitochondrial ROS levels compared to SSWT. The redox shift is also evident by the presence of more pronounced medullar lipid peroxidation in the SSNPPA−/− strain. We also revealed fragmented, more damaged mitochondria in the SSNPPA−/− rats, accompanied by increased turnover and biogenesis. Overall, our data indicate that ANP deficiency causes disruptions in mitochondrial bioenergetics and dynamics which likely contributes to aggravation of the renal damage and hypertension in the Dahl SS rat; the major pathological effects are evident in the groups subjected to a combined salt and ANP deficiency‐induced mitochondrial stress. We hypothesized in this study that Atrial Natriuretic Peptide (ANP) deficiency in the Dahl SS rat causes renal bioenergetic shift, amplifying oxidative stress. Our data indicate that lack of ANP disrupts mitochondrial bioenergetics and dynamics in the kidney, which likely contributes to aggravation of the renal disease in the Dahl SS rat.
Bibliography:	Alena Cherezova, Anastasia Sudarikova and Valeriia Vasileva contributed equally to this work. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0892-6638 1530-6860 1530-6860
DOI:	10.1096/fj.202400672RR