Friederich-Persson 2020 Am J Physiol Renal Physiol
Friederich-Persson M, Persson P (2020) Mitochondrial angiotensin II receptors regulate oxygen consumption in kidney mitochondria from healthy and type 1 diabetic rats. Am J Physiol Renal Physiol 318:F683-88. |
Friederich-Persson Malou, Persson Patrik (2020) Am J Physiol Renal Physiol
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 and type 2 receptors (AT1 receptor and AT2 receptor) 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 pre-incubation 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 nitric oxide synthase inhibitor L-NAME. AT1 receptor inhibition did not affect the response to Ang II, whereas AT2 receptor inhibition abolished the response in mitochondria from control animals and reversed the response to increased oxygen consumption through superoxide-induced mitochondrial uncoupling in mitochondria from diabetic rat.
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. β’ Keywords: AT1 receptor, AT2 receptor, Streptozotocin, Superoxide anions, Uncoupling protein β’ Bioblast editor: Plangger M β’ O2k-Network Lab: SE Uppsala Liss P
Labels: MiParea: Respiration, Pharmacology;toxicology
Pathology: Diabetes
Organism: Rat Tissue;cell: Kidney Preparation: Isolated mitochondria Enzyme: Uncoupling protein
Coupling state: LEAK, OXPHOS Pathway: N, Gp HRR: Oxygraph-2k
Labels, 2020-01