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Abstract: SA-PO762

Insights Into the Role of Atrial Natriuretic Peptide in Mitochondria-Mediated Metabolism in Salt-Sensitive (SS) Hypertension

Session Information

  • Hypertension and CVD: Mechanisms
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

  • 1503 Hypertension and CVD: Mechanisms

Authors

  • Zamaro, Aleksandra, Augusta University, Augusta, Georgia, United States
  • Cherezova, Alena, Augusta University, Augusta, Georgia, United States
  • Sultanova, Regina F., Medical University of South Carolina, Charleston, South Carolina, United States
  • Schibalski, Ryan, Augusta University, Augusta, Georgia, United States
  • Domondon, Mark, Augusta University, Augusta, Georgia, United States
  • Spicer, Morgan J., Augusta University, Augusta, Georgia, United States
  • Nikiforova, Anna, Medical University of South Carolina, Charleston, South Carolina, United States
  • Fomin, Mikhail, Augusta University, Augusta, Georgia, United States
  • Christopher, Courtney J., University of Tennessee Knoxville, Knoxville, Tennessee, United States
  • Campagna, Shawn R., University of Tennessee Knoxville, Knoxville, Tennessee, United States
  • Stadler, Krisztian, Pennington Biomedical Research Center, Baton Rouge, Louisiana, United States
  • Ilatovskaya, Daria, Augusta University, Augusta, Georgia, United States
Background

Salt-sensitive (SS) hypertension (SS-HTN) is associated with decreased levels of Atrial Natriuretic Peptide (ANP), and is accompanied with renal mitochondrial dysfunction. Although ANP has been proposed as a modulator of mitochondrial bioenergetics, its role in renal mitochondrial function in SS hypertension is unclear. The present study was aimed at identifying renal metabolic pathways affected in the condition of ANP deficiency modeled in a Dahl SS rat.

Methods

Dahl SS wild type (WT) and ANP knockout (KO) rats were placed on a 0.4% NaCl normal salt (NS) diet, or a 4% NaCl high salt (HS, to induce hypertension) for 21 days. Metabolic profiles of renal cortices were generated using UHPLC-HRMS, and metabolites were identified by retention time exact mass using MAVEN and MetaboAnalyst software. IPA was used to identify pathways of interest. Mitochondrial membrane potential, production of H2O2 and respiration were measured on isolated renal cortical mitochondria.

Results

133 mitochondria-associated metabolites were identified in the kidney cortices. When KO and WT groups were compared on NS, in the KO we observed increased abundance of amino acids and their metabolites (p<0.01) as well as uric acid cycle metabolites (citrulline, ornithine, acetylglutamine, p<0.01). Furthermore, we report elevated products of glycolysis in the KO (phosphoenolpyruvate, p<0.01, pyruvate, p<0.05), and significantly lower abundance of purines (ADP, GMP, UMP, p<0.01). Interestingly, KO tissues exhibited low levels of NAD+ and NADP+ (p<0.01). We observed similar metabolic processes in the WT rats when HS diet rats were compared to NS diet fed rats. Studies on isolated mitochondria revealed a decrease in membrane potential accompanied with higher OCR and superoxide production in the KO animals on both NS and HS diets, vs WT groups.

Conclusion

It can be surmised that lack of ANP in the Dahl SS rats triggers a potential renal glycolytic shift and activation of catabolic pathways. These data support the notion that changes in ANP levels modulate mitochondrial bioenergetics in SS-HTN, and further studies of the related pathways will lead to a discovery of novel therapeutics.

Funding

  • Other NIH Support