• Ebba Sivertsson, Amanda Balboa, Tomas A Schiffer, Peter Hansell, Malou Friederich-Persson, Patrik Persson, and Fredrik Palm.
• Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
• Ups. J. Med. Sci. 2023 Jan 1; 128.

BackgroundIntrarenal hypoxia has been suggested a unifying pathway to chronic kidney disease (CKD) and increased mitochondria leak respiration, which increases mitochondrial oxygen usage and is one important mechanism contributing to the development of the hypoxia. Previous studies indicate that angiotensin II (Ang II) effects on mitochondria function could be dose dependent. We investigated how moderate and high levels of Ang II affect kidney mitochondria function and pathways of leak respiration.MethodsC57 black 6 mice were treated with either vehicle or Ang II in low dose (400 ng/kg/min) or high dose (1,000 ng/kg/min) for 4 weeks. The function of kidney cortex mitochondria was measured by high-resolution respirometry. Ang II effects on gene expression in kidney tissue were measured by quantitative real-time PCR. Thiobarbituric acids reactive substances were determined as a marker of oxidative stress, and urinary protein excretion was measured as a maker of kidney injury.ResultsLow-dose Ang II induced overall mitochondria respiration, without compromising capacity of ATP production. Mitochondrial leak respiration was increased, and levels of oxidative stress were unchanged. However, high-dose Ang II decreased overall mitochondria respiration and reduced mitochondrial capacity for ATP production. Mitochondrial leak respiration was decreased, and oxidative stress increased in kidney tissue. Furthermore, gene expression of mediators that stimulate vasoconstriction and ROS production was increased, while components of counteracting pathways were decreased.ConclusionsIn conclusion, Ang II dose-dependently affects mitochondrial function and leak respiration. Thus, Ang II has the potential to directly affect cellular metabolism during conditions of altered Ang II signaling.© 2023 The Author(s). Published by Upsala Medical Society.

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