Abstract
It has previously been proved that sodium nitrite, infused prior to coronary artery occlusion or before reperfusion, results in marked antiarrhythmic effect in anaesthetized dogs. We have now examined whether this protection involves the modulation of gap junction (GJ) function by nitric oxide (NO), derived from nitrite administration under ischaemic conditions. Two groups of chloralose and urethane anaesthetized dogs, each containing 13 animals, were subjected to a 25 min period occlusion of the left anterior descending (LAD) coronary artery, followed by reperfusion. One group was infused with sodium nitrite (0.2 μmol/kg/min, i.v.), the other group with saline 10 min prior to reperfusion. The severities of arrhythmias and of ischaemia (epicardial ST-segment, total activation time), parallel with changes in myocardial tissue impedance, a measure of electrical coupling of gap junctions, were assessed during the experiments. Compared to the controls, nitrite infusion administered prior to reperfusion significantly attenuated the severity of ischaemia, the ischaemia-induced impedance changes and, consequently, the severity of arrhythmias, occurring during the 1B phase of the occlusion, and increase survival following reperfusion (0% vs. 85%). It is concluded that the marked antiarrhythmic effect of sodium nitrite is partly due, to the preservation of the electrical coupling of GJs by NO.
Article PDF
Similar content being viewed by others
Explore related subjects
Discover the latest articles, news and stories from top researchers in related subjects.Avoid common mistakes on your manuscript.
References
Babai, L., Szigeti, Z., Parratt, J. R., Végh, Á. (2002) Delayed cardioprotective effects of exercise in dogs are aminoguanidine sensitive: possible involvement of nitric oxide. Clin. Sci. 102, 435–445.
Beardslee, M. A., Lerner, D. L., Tadros, P. N., Laing, J. G., Beyer, E. C., Yamada, K. A. et al. (2000) Dephosphorylation and intracellular redistribution of ventricular connexin 43 during electrical uncoupling induced by ischemia. Circ. Res. 87, 656–662.
Burwell, L. S., Brookes, P. S. (2008) Mitochondria as a target for the cardioprotective effects of nitric oxide in ischemia-reperfusion injury. Antioxid. Redox. Signal 10, 579–599.
Duranski, M. R., Greer, J. J., Dejam, A., Jaganmohan, S., Hogg, N., Langston, W. et al. (2005) Cytoprotective effects of nitrite during in vivo ischemia-reperfusion of the heart and liver. J. Clin. Invest. 115, 1232–1240.
Gonzalez, F. M., Shiva, S., Vincent, P. S., Ringwood, L. A., Hsu, L. Y., Hon, Y. Y. et al. (2008) Nitrite anion provides potent cytoprotective and anti-apoptotic effects as adjunctive therapy to reperfusion for acute myocardial infarction. Circulation 117, 2986–2994.
Gönczi, M., Papp, R., Kovács, M., Seprényi, Gy., Végh, Á. (2009) Modulation of gap junctions by nitric oxide contributes to the antiarrhythmic effect of sodium nitroprusside. Br. J. Pharmacol. 156, 786–793.
Iwase, H., Robin, E., Guzy, R. D., Mungai, P. T., Vanden Hoek, T. L., Chandel, N.S. et al. (2007) Nitric oxide during ischemia attenuates oxidant stress and cell death during ischemia and reperfusion in cardiomyocytes. Free Radial. Biol. Med. 43, 590–599.
Jongsma, H. J., Wilders, R. (2000) Gap junctions in cardiovascular disease. Circ. Res. 86, 1193–1197.
Kevil, C. G., Lefer, D. J. (2011) Review focus on inorganic nitrite and nitrate in cardiovascular health and disease. Cardiovasc. Res. 89, 489–491.
Kevil, C. G., Kolluru, G. K., Pattillo, C. B., Giordano, T. (2011) Inorganic nitrite therapy: historical perspective and future directions. Free Radical Biol. Med. 51, 576–593.
Kis, A., Végh, Á., Papp, J. Gy., Parratt, J. R. (1999) Repeated cardiac pacing extends the time during which canine hearts are protected against ischaemia-induced arrhythmias: role of nitric oxide. J. Mol. Cell. Cardiol. 31, 1229–1241.
Kiss, A., Juhász, L., Seprényi, Gy., Kupai, K., Kaszaki, J., Végh, Á. (2010) The role of nitric oxide, superoxide and peroxynitrite in the anti-arrhythmic effects of preconditioning and peroxynitrite infusion in anaesthetized dogs. Br. J. Pharmacol. 160, 1263–1272.
Kohr, M. J., Sun, J., Aponte, A., Wang, G., Gucek, M., Murphy, E. et al. (2011) Simultaneous measurement of protein oxidation and S-nitrosylation during preconditioning and ischemia/reperfusion injury with resin-assisted capture. Circ. Res. 108, 418–426.
Kovács, M., Kiss, A., Gönczi, M., Miskolczi, M., Seprényi, Gy., Kaszaki, J., Kohr, M., Murphy, E., Végh, Á. (2015) Effect of sodium nitrite on ischaemia and reperfusion-induced arrhythmias in anaesthetized dogs: Is protein S-nitrosylation involved? Plos One 24; 10: e0122243.
Lefer, D. J. (2006) Nitrite therapy for protection against ischemia-reperfusion injury. Am. J. Physiol. Renal Physiol. 290, F777–F778.
Lefer, D. J., Nakanishi, K., Vinten-Johansen, J. (1993) Endothelial and myocardial cell protection by a cysteine-containing nitric oxide donor after myocardial ischaemia and reperfusion. J. Cardiovasc. Pharmacol. 22, S34–S43.
Lundberg, J. O., Carlström, M., Larsen, F. J., Weitzberg, E. (2011) Roles of dietary inorganic nitrate in cardiovascular health and disease. Cardiovasc. Res. 89, 525–532.
Méry, P. F., Pavoine, C., Belhassen, L., Pecker, F., Fishcmeister, R. (1993) Nitric oxide regulates cardiac Ca2+ current. Involvement of cGMP-inhibited and cGMP-stimulated phosphodiesterases through guanylyl cyclase activation. J. Biol. Chem. 268, 26286–26295.
Miskolczi, G., Gönczi, M., Kovács, M., Seprényi, Gy., Végh, Á. (2015) Further evidence for the role of gap junctions in the delayed antiarrhythmic effect of cardiac pacing. Can. J. Physiol. Pharmacol. 93, 545–553.
Papp, R., Gönczi, M., Kovács, M., Seprényi, Gy., Végh, Á. (2007) Gap junctional uncoupling plays a trigger role in the antiarrhythmic effect of ischaemic preconditioning. Cardiovasc. Res. 74, 396–405.
Smith, W. T., Fleet, W. F., Johnson, T. A., Engle, C. L., Cascio, W. E. (1995) The 1b phase of ventricular arrhythmias in ischemic in situ porcine heart is related to changes in cell-to-cell electrical coupling. Circulation 92, 3051–3060.
Végh, Á., Gönczi, M., Miskolczi, G., Kovács, M. (2013) Regulation of gap junctions by nitric oxide influences the generation of arrhythmias resulting from acute ischemia and reperfusion in vivo. Frontiers in Pharmacology 4, 76–82.
Végh, Á., Komori, S., Szekeres, L., Parratt, J. R. (1992) Antiarrhythmic effects of preconditioning in anaesthetised dogs and rats. Cardiovasc. Res. 26, 487–495.
Végh, Á., Papp, R. (2011) Possible mechanisms of the acute ischemia-induced ventricular arrhythmias: the involvement of gap junctions. In: Tripathi, O. N., Ravens, U., Sanguinetti, M. C. (eds) Heart Rate and Rhythm. Molecular Basis, Pharmacological Modulation and Clinical Applications, Springer-Verlag, Berlin Heidelberg, pp. 525–543.
Végh, Á., Papp, J. Gy., Parratt, J. R. (1994) Prevention by dexamethasone of the marked antiarrhythmic effects of preconditioning induced 20 h after rapid cardiac pacing. Br. J. Pharmacol. 113, 1081–1082.
Végh, Á., Szekeres, L., Parratt, J. R. (1992) Preconditioning of the ischaemic myocardium; involvement of the L-arginine–nitric oxide pathway. Br. J. Pharmacol. 107, 648–652.
Walker, M. J. A., Curtis, M. J., Hearse, D. J., Campbell, R. W. F., Janse, M. J., Yellon, D. M., Cobbe, S. M., Coker, S. J., Harness, J. B., Harron, D. W. G., Higgins, A. J., Julian, D. G., Lab, M. J., Manning, A. S., Northover, B. J., Parratt, J. R., Riemersma, R. A., Riva, E., Russell, D. C., Sheridan, D. J., Winslow, E., Woodward, B. (1988) The Lambeth Conventions: guidelines for the study of arrhythmias in ischaemia, infarction, and reperfusion. Cardiovasc. Res. 22, 447–455.
Webb, A., Bond, R., McLean, P., Uppal, R., Benjamin, N., Ahluwalia, A. (2004) Reduction of nitrite to nitric oxide during ischemia protects against myocardial ischemia-reperfusion damage. Proc. Natl Acad. Sci. USA 101, 13683–13688.
White, R. L., Doeller, J. E., Verselis, V. K., Wittenberg, B. A. (1990) Gap junctional conductance between pairs of ventricular myocytes is modulated synergistically by H+ and Ca++. J. Gen. Physiol. 95, 1061–1075.
Zweier, J. L., Wang, P., Samouilov, A., Kuppusamy, P. (1995) Enzyme-independent formation of nitric oxide in biological tissues. Nature Medicine 1, 804–809.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
About this article
Cite this article
Miskolczi, G., Gönczi, M., Kovács, M. et al. Examination of the Effect of Sodium Nitrite on Gap Junction Function During Ischaemia and Reperfusion in Anaesthetized Dogs. BIOLOGIA FUTURA 68, 35–49 (2017). https://doi.org/10.1556/018.68.2017.1.4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1556/018.68.2017.1.4