Mitochondrial morphological changes and electron transport chain (ETC) uncoupling induced by Angiotensin II (Ang II) in neuronal cells of the subfornical organ (SFO) and cultured neural cells

• Published in: The FASEB journal 2013-04, Vol.27 (S1)
• Main Authors: Sarkar, Pallabi, Young, Colin N, Pierce, Joseph P, Zhou, Ping, Iadecola, Costantino, Davisson, Robin L
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.27.1_supplement.lb846

Abstract only The SFO plays a critical role in the development of hypertension in response to elevated levels of circulating Ang II. Recent evidence suggests that in peripheral tissues and in brain regions involved in cardiovascular regulation, Ang II causes mitochondrial dysfunction that is often accompanied by morphological changes. Here we tested the hypothesis that in the SFO and in Neuro‐2A cells, Ang II causes both morphological and functional changes in the mitochondria. Osmominipumps were inserted in C57BL6 mice for infusion of Ang‐II (600 ng/kg/min) or vehicle for 14 days. Brains were then harvested for electron microscopy (EM). EM revealed that SFO neurons in the Ang II group exhibited reduced area per mitochondrial profile (vehicle 93740 ± 6348 μm2; Ang II 76287 ± 3527 μm2; p < 0.05; n=81–109) and increased number of mitochondria per unit area (Ang II 9.9 ± 1.3; vehicle 6.6 ± 0.8, p < 0.05), indicating reduction in size. For assessment of mitochondrial function, Neuro‐2A cells were incubated with Ang II (300 nM, 24 h) for O 2 consumption measurement. Ang II altered mitochondrial respiration (1.63±0.2 nmol/min/mg; vehicle 1.03±0.2, p < 0.05) and reduced the ETC coupling ratio (54 ± 12%, p < 0.05). These findings suggest that Ang II induces alterations in mitochondrial size and bioenergetics that may play a role in the mechanisms by which SFO neurons contributes to Ang II‐dependent hypertension. HL63887, HL96571, HL84207