Low concentrations of an nitric oxide-donor combined with a liposoluble antioxidant compound enhance protection against reperfusion injury in isolated rat hearts

• Autorzy: Rastalo R. , Cappello S. , Folino A. , Di Stilo A. , Chegaev K. , Tritto I. , Pagliaro P. , Losano G.
• Języki publikacji: EN

Abstrakty

EN

Nitric oxide (NO) and reactive oxygen species (ROS) are double-edged swords in reperfused hearts. The effects of a NO-donor and an antioxidant compound against ischemia/reperfusion were studied. The compounds were tested separately, as a mixture and as a new hybrid molecule containing both leads. Isolated rat hearts underwent 30 min global ischemia and 2 hrs reperfusion. Compounds were infused either at 1 or 10 µM concentrations during the first 20 min of reperfusion. Hybrid was also tested in the presence of mitochondrial K+ ATP-sensitive (mKATP) channel blockade by 5-HD (100 µM). Reduction of infarct size and recovery of left ventricular developed pressure during reperfusion were evaluated. When given at 1 µM concentration, hybrid significantly improved all indices of protection; its beneficial effects were abolished by mKATP channel blockade. At the same concentration, mixture and NO-donor alone improved recovery of left ventricular developed pressure but did not reduce infarct size; antioxidant was ineffective. When given at 10 µM concentration, antioxidant and mixture improved all parameters of protection; NO-donor and hybrid were ineffective. Our data suggest that different signaling cascades could be elicited by low and high concentrations of antioxidant compound and/or NO-donor. It is likely that a different NO-induced release of reactive oxygen species via mKATP channel activation may play a pivotal role in affecting infarct size and post-ischemic contractile recovery.

Słowa kluczowe

EN

low concentration; nitric oxide; liposoluble antioxidant; antioxidant; rat; heart; reactive oxygen species; ischaemia-reperfusion; myocardial protection; infarct size

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 2010
• Tom: 61
• Numer: 1
• Opis fizyczny: p.21-27,fig.,ref.

Twórcy

autor

Rastalo R.

• Facolta di Medicina e Chirurgia "S. Luigi Gonzaga", Regione Gonzole 10, 10043 Orbassano [TO], Italy

autor

Cappello S.

autor

Folino A.

autor

Di Stilo A.

autor

Chegaev K.

autor

Tritto I.

autor

Pagliaro P.

autor

Losano G.

Bibliografia

• Braunwald E, Kloner RA. Myocardial reperfusion: a double-edged sword?. J Clin Invest 1985; 76: 1713-1719.
• Ambrosio G, Tritto I. Reperfusion injury: experimental evidence and clinical implications. Am Heart J 1999; 138: S69-S75.
• Zhao ZQ, Corvera JS, Halkos ME, et al. Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic pre-conditioning. Am J Physiol Heart Circ Physiol 2003; 285: H579-H588.
• Beresewicz A, Maczewski M, Duda M. Effect of classic preconditioning and diazoxide on endothelial function and O2- and NO generation in the post-ischemic guinea-pig heart. Cardiovasc Res 2004; 63: 118-129.
• Tsang A, Hausenloy DJ, Mocanu MM, Yellon DM. Postconditioning: a form of "modified reperfusion" protects the myocardium by activating the phosphatidylinositol 3-kinase-Akt pathway. Circ Res 2004; 95: 230-232.
• Boschi D, Tron GC, Lazzarato L, et al. NO-donor phenols: a new class of products endowed with antioxidant and vasodilator properties. J Med Chem 2006; 49: 2886-2897.
• Flaherty JT, Pitt B, Gruber JW, et al. Recombinant human superoxide dismutase (h-SOD) fails to improve recovery of ventricular function in patients undergoing coronary angioplasty for acute myocardial infarction. Circulation 1994; 89: 1982-1991.
• Vinten-Johansen J, Zhao ZQ, Zatta AJ, Kin H, Halkos ME, Kerendi F. Postconditioning - a new link in nature's armor against myocardial ischemia-reperfusion injury. Basic Res Cardiol 2005; 100: 295-310.
• Hoffman JW Jr, Gilbert TB, Poston RS, Silldorff EP. Myocardial reperfusion injury: etiology, mechanisms, and therapies. J Extra Corpor Technol 2004; 36: 391-411.
• Marchioli R, Levantesi G, Macchia A, et al. Vitamin E increases the risk of developing heart failure after myocardial infarction: results from the GISSI-Prevenzione Trial. J Cardiovasc Med (Hagerstown) 2006; 7: 347-350.
• Bolli R. Cardioprotective function of inducible nitric oxide synthase and role of nitric oxide in myocardial ischemia and preconditioning: an overview of research. J Mol Cell Cardiol 2001; 33: 1897-918.
• Schulz R, Kelm M, Heusch G. Nitric oxide in myocardial ischemia/reperfusion injury. Cardiovasc Res 2004; 61: 402-413.
• Penna C, Rastaldo R, Mancardi D, et al. Post-conditioning induced cardioprotection requires signaling through a redox-sensitive mechanism, mitochondrial ATP-sensitive K+ channel and protein kinase C activation. Basic Res Cardiol 2006; 101: 180-189.
• Hausenloy DJ, Wynne AM, Yellon DM. Ischemic preconditioning targets the reperfusion phase. Basic Res Cardiol 2007;102: 445-452.
• Penna C, Mancardi D, Rastaldo R, Losano G, Pagliaro P. Intermittent activation of bradykinin B2 receptors and mitochondrial KATP channels trigger cardiac postconditioning through redox signaling. Cardiovasc Res 2007; 75: 168-177
• Tsutsumi YM, Yokoyama T, Horikawa Y, Roth DM, Patel HH. Reactive oxygen species trigger ischemic and pharmacological postconditioning: in vivo and in vitro characterization. Life Sci 2007; 81: 1223-1227.
• Liu Y, Yang XM, Iliodromitis EK, et al. Redox signaling at reperfusion is required for protection from ischemic preconditioning but not from a direct PKC activator. Basic Res Cardiol 2008; 103: 54-59.
• Rastaldo R, Pagliaro P, Cappello S, et al. Nitric oxide and cardiac function. Life Sci 2007; 81: 779-793.
• Penna C, Mognetti B, Tullio F, et al. The platelet activating factor triggers preconditioning-like cardioprotective effect via mitochondrial K-ATP channels and redox-sensible signaling. J Physiol Pharmacol 2008; 59: 47-54.
• Wang G, Liem DA, Vondriska TM, et al. Nitric oxide donors protect murine myocardium against infarction via modulation of mitochondrial permeability transition. Am J Physiol Heart Circ Physiol 2005; 288: H1290-H1295.
• Oldenburg O, Qin Q, Krieg T, et al. Bradykinin induces mitochondrial ROS generation via NO, cGMP, PKG, and mitoKATP channel opening and leads to cardioprotection. Am J Physiol Heart Circ Physiol 2004; 286: H468-H476.
• Penna C, Mancardi D, Rastaldo R, Pagliaro P. Cardioprotection: a radical view free radicals in pre- and postconditioning. Biochim Biophys Acta 2009; 1797: 781-793.
• Tritto I, D'Andrea D, Eramo N, et al. Oxygen radicals can induce preconditioning in rabbit hearts. Circ Res 1997; 80: 743-748.
• Kutala VK, Khan M, Mandal R, et al. Prevention of postischemic myocardial reperfusion injury by the combined treatment of NCX-4016 and Tempol. J Cardiovasc Pharmacol 2006; 48: 79-87.
• Hausenloy DJ, Yellon DM. Preconditioning and postconditioning: united at reperfusion. Pharmacol Ther 2007; 116: 173-191.
• Downey JM, Cohen MV. Free radicals in the heart: friend or foe? Expert Rev Cardiovasc Ther 2008; 6: 589-591.
• Zhao ZQ. Oxidative stress-elicited myocardial apoptosis during reperfusion. Curr Opin Pharmacol 2004; 4: 159-165.
• Kojda G, Kottenberg K. Regulation of basal myocardial function by NO. Cardiovasc Res 1999; 41: 514-523.
• Massion PB, Balligand, JL. Modulation of cardiac contraction, relaxation and rate by the endothelial nitric oxide synthase (eNOS): lessons from genetically modified mice. J Physiol 2003; 546: 63-75.
• S Kwiecien S, Pawlik MW, Brzozowski T, et al. Nitric oxide (NO)-releasing aspirin and (NO) donors in protection of gastric mucosa against stress. J Physiol Pharmacol 2008; 59: 103-115.
• Kristek F, Koprdova R, Cebova M. Long-term effects of early administered sildenafil and NO donor on the cardiovascular system of SHR. J Physiol Pharmacol 2007; 58: 33-43.
• Dovinova I, Cacanyiova S, Faberova V, Kristek F. The effect of an NO donor, pentaerythrityl tetranitrate, on biochemical, functional, and morphological attributes of cardiovascular system of spontaneously hypertensive rats. Gen Physiol Biophys 2009; 28: 86-93.
• Rubbo H, Radi R, Anselmi D, et al. Nitric oxide reaction with lipid peroxyl radicals spares alpha-tocopherol during lipid peroxidation. Greater oxidant protection from the pair nitric oxide/alpha-tocopherol than alpha-tocopherol/ascorbate. J Biol Chem 2000; 275: 10812-10818.