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  • 1 University of Szeged, Dóm tér 12, H-6721 Szeged, Hungary
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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.

  • 1.

    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, 435445.

    • Search Google Scholar
    • Export Citation
  • 2.

    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, 656662.

    • Search Google Scholar
    • Export Citation
  • 3.

    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, 579599.

    • Search Google Scholar
    • Export Citation
  • 4.

    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, 12321240.

    • Search Google Scholar
    • Export Citation
  • 5.

    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, 29862994.

    • Search Google Scholar
    • Export Citation
  • 6.

    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, 786793.

    • Search Google Scholar
    • Export Citation
  • 7.

    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, 590599.

    • Search Google Scholar
    • Export Citation
  • 8.

    Jongsma, H. J., Wilders, R. (2000) Gap junctions in cardiovascular disease. Circ. Res. 86, 11931197.

  • 9.

    Kevil, C. G., Lefer, D. J. (2011) Review focus on inorganic nitrite and nitrate in cardiovascular health and disease. Cardiovasc. Res. 89, 489491.

    • Search Google Scholar
    • Export Citation
  • 10.

    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, 576593.

    • Search Google Scholar
    • Export Citation
  • 11.

    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, 12291241.

    • Search Google Scholar
    • Export Citation
  • 12.

    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, 12631272.

    • Search Google Scholar
    • Export Citation
  • 13.

    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, 418426.

    • Search Google Scholar
    • Export Citation
  • 14.

    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.

    • Search Google Scholar
    • Export Citation
  • 15.

    Lefer, D. J. (2006) Nitrite therapy for protection against ischemia-reperfusion injury. Am. J. Physiol. Renal Physiol. 290, F777F778.

    • Search Google Scholar
    • Export Citation
  • 16.

    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, S34S43.

    • Search Google Scholar
    • Export Citation
  • 17.

    Lundberg, J. O., Carlström, M., Larsen, F. J., Weitzberg, E. (2011) Roles of dietary inorganic nitrate in cardiovascular health and disease. Cardiovasc. Res. 89, 525532.

    • Search Google Scholar
    • Export Citation
  • 18.

    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, 2628626295.

    • Search Google Scholar
    • Export Citation
  • 19.

    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, 545553.

    • Search Google Scholar
    • Export Citation
  • 20.

    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, 396405.

    • Search Google Scholar
    • Export Citation
  • 21.

    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, 30513060.

    • Search Google Scholar
    • Export Citation
  • 22.

    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, 7682.

    • Search Google Scholar
    • Export Citation
  • 23.

    Végh, Á., Komori, S., Szekeres, L., Parratt, J. R. (1992) Antiarrhythmic effects of preconditioning in anaesthetised dogs and rats. Cardiovasc. Res. 26, 487495.

    • Search Google Scholar
    • Export Citation
  • 24.

    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. 525543.

    • Search Google Scholar
    • Export Citation
  • 25.

    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, 10811082.

    • Search Google Scholar
    • Export Citation
  • 26.

    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, 648652.

    • Search Google Scholar
    • Export Citation
  • 27.

    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, 447455.

    • Search Google Scholar
    • Export Citation
  • 28.

    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, 1368313688.

    • Search Google Scholar
    • Export Citation
  • 29.

    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, 10611075.

    • Search Google Scholar
    • Export Citation
  • 30.

    Zweier, J. L., Wang, P., Samouilov, A., Kuppusamy, P. (1995) Enzyme-independent formation of nitric oxide in biological tissues. Nature Medicine 1, 804809.

    • Search Google Scholar
    • Export Citation