Mitochondrial angiotensin II receptors regulate oxygen consumption in kidney mitochondria from healthy and type 1 diabetic rats - PubMed (original) (raw)

. 2020 Mar 1;318(3):F683-F688.

doi: 10.1152/ajprenal.00417.2019. Epub 2020 Jan 6.

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Mitochondrial angiotensin II receptors regulate oxygen consumption in kidney mitochondria from healthy and type 1 diabetic rats

Malou Friederich-Persson et al. Am J Physiol Renal Physiol. 2020.

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Abstract

Exaggerated activation of the renin-angiotensin-aldosterone system (RAAS) is a key feature in diseases such as hypertension, diabetes, and chronic kidney disease. Recently, an intracellular RAAS was demonstrated with angiotensin II (ANG II) type 1 (AT1) and type 2 (AT2) receptors expressed in nuclei and mitochondria. Diabetes is associated with both mitochondrial dysfunction and increased intracellular ANG II concentration in the kidney cortex. The present study investigated the role of ANG II signaling in kidney cortex mitochondria isolated from control and streptozotocin-induced diabetic rats. Mitochondrial oxygen consumption was evaluated after addition of ANG II alone or after preincubation with candesartan (AT1 receptor antagonist), PD-123319 (AT2 receptor antagonist), or the two in combination. ANG II binds to only mitochondrial AT2 receptors in control rats and both AT1 receptors and AT2 receptors in diabetic rats. ANG II decreased oxygen consumption in mitochondria from both control and diabetic rats. ANG II response was reversed to increased oxygen consumption by the nitric oxide synthase inhibitor _N_-nitro-l-arginine methyl ester. AT1 receptor inhibition did not affect the response to ANG II, whereas AT2 receptor inhibition abolished the response in mitochondria from control rats and reversed the response to increased oxygen consumption through superoxide-induced mitochondrial uncoupling in mitochondria from diabetic rats. ANG II decrease mitochondrial respiration via AT2 receptor-mediated nitric oxide release in both control and diabetic rats. AT1 receptors do not regulate mitochondria function in control rats, whereas ANG II via AT1 receptors increase mitochondria leak respiration in diabetic animals.

Keywords: angiotensin II type 1 receptor; angiotensin II type 2 receptor; mitochondrial uncoupling; streptozotocin; superoxide.

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