ORIGINAL RESEARCH published: 28 March 2018 doi: 10.3389/fphar.2018.00286 Frontiers in Pharmacology | www.frontiersin.org 1 March 2018 | Volume 9 | Article 286 Edited by: Aida Salameh, Leipzig University, Germany Reviewed by: Jan Sebastian Schulte, Universität Münster, Germany Saradhadevi Varadharaj, Abbott, United States *Correspondence: Mária Kovács kovacsmaria.m@gmail.com Specialty section: This article was submitted to Cardiovascular and Smooth Muscle Pharmacology, a section of the journal Frontiers in Pharmacology Received: 15 November 2017 Accepted: 13 March 2018 Published: 28 March 2018 Citation: Demeter-Haludka V, Kovács M, Petrus A, Patai R, Muntean DM, Siklós L and Végh Á (2018) Examination of the Role of Mitochondrial Morphology and Function in the Cardioprotective Effect of Sodium Nitrite Administered 24 h Before Ischemia/Reperfusion Injury. Front. Pharmacol. 9:286. doi: 10.3389/fphar.2018.00286 Examination of the Role of Mitochondrial Morphology and Function in the Cardioprotective Effect of Sodium Nitrite Administered 24 h Before Ischemia/Reperfusion Injury Vivien Demeter-Haludka 1 , Mária Kovács 1 *, Alexandra Petrus 2 , Roland Patai 3 , Danina M. Muntean 2 , László Siklós 3 and Ágnes Végh 1 1 Department of Pharmacology and Pharmacotherapy, Albert-Szent Györgyi Medical Centre, University of Szeged, Szeged, Hungary, 2 Department of Pathophysiology, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania, 3 Department of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary Background: We have previous evidence that in anesthetized dogs the inorganic sodium nitrite protects against the severe ventricular arrhythmias, resulting from coronary artery occlusion and reperfusion, when administered 24 h before. The present study aimed to examine, whether in this effect changes in mitochondrial morphology and function would play a role. Methods: Thirty dogs were infused intravenously either with saline (n = 15) or sodium nitrite (0.2 μmol/kg/min; n = 15) for 20 min, and 24 h later, 10 dogs from each group were subjected to a 25 min period of occlusion and then reperfusion of the left anterior descending coronary artery. The severity of ischaemia and ventricular arrhythmias were examined in situ. Left ventricular tissue samples were collected either before the occlusion (5 saline and 5 nitrite treated dogs) or, in dogs subjected to occlusion, 2min after reperfusion. Changes in mitochondrial morphology, in complex I and complex II-dependent oxidative phosphorylation (OXPHOS), in ATP, superoxide, and peroxynitrite productions were determined. Results: The administration of sodium nitrite 24 h before ischemia/reperfusion significantly attenuated the severity of ischaemia, and markedly reduced the number and incidence of ventricular arrhythmias. Nitrite also attenuated the ischaemia and reperfusion (I/R)-induced structural alterations, such as reductions in mitochondrial area, perimeter, and Feret diameter, as well as the increase in mitochondrial roundness. The administration of nitrite, however, enhanced the I/R-induced reduction in the mitochondrial respiratory parameters; compared to the controls, 24 h after the infusion of nitrite, there were further significant decreases, e.g., in the complex I-dependent OXPHOS (by −20 vs. −53%), respiratory control ratio (by −14 vs. −61%) and in the P/E control coupling ratio (by 2 vs. −36%). Nitrite also significantly reduced the I/R-induced generation of superoxide, without substantially influencing the ATP production.