PL EN


Preferences help
enabled [disable] Abstract
Number of results
2007 | 54 | 1 | 199-204
Article title

A poly(ADP-ribose) synthetase inhibitor, benzamide protects smooth muscle cells but not endothelium against ischemia/reperfusion injury in isolated guinea-pig heart

Content
Title variants
Languages of publication
EN
Abstracts
EN
Activation of the nuclear enzyme poly(ADP-ribose) synthethase (PARS) is important in the cellular response to oxidative stress. During ischemia and reperfusion (I/R) increased free radical production leads to DNA breakage that stimulates PARS which in turn results in an energy-consuming metabolic cycle and initiation of the apoptotic process. Previous studies have reported that PARS inhibition confers protection in various models of I/R-induced cardiovascular damage. The purpose of this study was to determine the role of PARS inhibition in I/R-induced injury of smooth muscle cells and endothelium in the coronary circulation of the isolated guinea-pig heart. Control hearts and those treated with a PARS inhibitor - benzamide (100 µmol L-1), were subjected to 30 min of subglobal ischemia and subsequent reperfusion (90 min). To analyze the functional integrity of smooth muscle cells and endothelium, one-minute intracoronary infusions of endothelium-independent (sodium nitroprusside, NaNP; 3 µmol L-1) and endothelium-dependent (substance P, SP; 10 nmol L-1) vasodilators were used before ischemia and at the reperfusion time. The degree of the injury of coronary smooth muscle and endothelial cells induced by I/R was estimated in terms of diminished vasodilator responses to NaNP (at 55 min and 85 min of reperfusion) and to SP (at 70 min of reperfusion), respectively, and expressed as the percentage of preischemic response. I/R reduced vasorelaxant responses to both vasodilators by half (to 54.1 ± 5.1% and to 53.6 ± 4.9% of preischemic value for NaNP at 55 min and 85 min of reperfusion, respectively and to 45.9 ± 6.5% for SP at 70 min of reperfusion). PARS inhibition provided complete restoration of vasorelaxation induced by NaNP (107.6 ± 13.3% and 104 ± 14.4% of preischemic response at the two time points of reperfusion, respectively). However, there was no effect on the SP-induced response (48+12.1% of preischemic response). We conclude that pharmacological PARS inhibition with benzamide protects coronary smooth muscle cells but not endothelium against I/R-induced reperfusion injury in the coronary circulation of the guinea-pig heart.
Publisher

Year
Volume
54
Issue
1
Pages
199-204
Physical description
Dates
published
2007
received
2006-04-12
revised
2007-02-26
accepted
2007-03-08
(unknown)
2007-03-20
Contributors
  • Department of Experimental Pharmacology, Chair of Pharmacology, Medical College of the Jagiellonian University, Kraków, Poland
  • Department of Experimental Pharmacology, Chair of Pharmacology, Medical College of the Jagiellonian University, Kraków, Poland
References
  • Andrasi TB, Blazovics A, Szabo G, Vahl CF, Hagl S (2005) Poly(ADP-ribose) polymerase inhibitor PJ-34 reduces mesenteric vascular injury induced by experimental cardiopulmonary bypass with cardiac arrest. Am J Physiol Heart Circ Physiol 288: H2972-H2978.
  • Bakondi E, Bai P, Szabo EE, Hunyadi J, Gergely P, Szabo C, Virag L (2002) Detection of poly(ADP-ribose) polymerase activation in oxidatively stressed cells and tissues using biotinylated NAD substrate. J Histochem Cytochem 50: 91-98.
  • Benko R, Pacher P, Vaslin A, Kollai M, Szabo C (2004) Restoration of the endothelial function in the aortic rings of apolipoprotein E deficient mice by pharmacological inhibition of the nuclear enzyme poly(ADP-ribose) polymerase. Life Sci 75: 1255-1261.
  • Chlopicki S, Gryglewski RJ (1993) Nitric oxide is a major mediator in reactive hyperaemia evoked by a brief coronary occlusion in the guinea pig heart. Eur J Pharmacol 241: 117-120.
  • D'Amours D, Desnoyers S, D'Silva I, Poirier GG (1999) Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions. Biochem J 342 (Pt 2): 249-268.
  • de Murcia G, Schreiber V, Molinete M, Saulier B, Poch O, Masson M, Niedergang C, Menissier de MJ (1994) Structure and function of poly(ADP-ribose) polymerase. Mol Cell Biochem 138: 15-24.
  • Farivar AS, McCourtie AS, Kinnon-Patterson BC, Woolley SM, Barnes AD, Chen M, Jagtap P, Szabo C, Salerno CT, Mulligan MS (2005) Poly (ADP) ribose polymerase inhibition improves rat cardiac allograft survival. Ann Thorac Surg 80: 950-956.
  • Gilad E, Zingarelli B, Salzman AL, Szabo C (1997) Protection by inhibition of poly (ADP-ribose) synthetase against oxidant injury in cardiac myoblasts in vitro. J Mol Cell Cardiol 29: 2585-2597.
  • Goodwin PM, Lewis PJ, Davies MI, Skidmore CJ, Shall S (1978) The effect of gamma radiation and neocarzinostatin on NAD and ATP levels in mouse leukaemia cells. Biochim Biophys Acta 543: 576-582.
  • Jacobson EL, Lange RA, Jacobson MK (1979) Pyridine nucleotide synthesis in 3T3 cells. J Cell Physiol 99: 417-425.
  • Jerome SN, Smith CW, Korthuis RJ (1993) CD18-dependent adherence reactions play an important role in the development of the no-reflow phenomenon. Am J Physiol 264: H479-H483.
  • Junod AF, Jornot L, Petersen H (1989) Differential effects of hyperoxia and hydrogen peroxide on DNA damage, polyadenosine diphosphate-ribose polymerase activity, and nicotinamide adenine dinucleotide and adenosine triphosphate contents in cultured endothelial cells and fibroblasts. J Cell Physiol 140: 177-185.
  • Lefer AM, Tsao PS, Lefer DJ, Ma XL (1991) Role of endothelial dysfunction in the pathogenesis of reperfusion injury after myocardial ischemia. FASEB J 5: 2029-2034.
  • Lindahl T, Satoh MS, Poirier GG, Klungland A (1995) Post-translational modification of poly(ADP-ribose) polymerase induced by DNA strand breaks. Trends Biochem Sci 20: 405-411.
  • Mehta JL, Nichols WW, Donnelly WH, Lawson DL, Thompson L, terRiet M, Saldeen TG (1989) Protection by superoxide dismutase from myocardial dysfunction and attenuation of vasodilator reserve after coronary occlusion and reperfusion in dog. Circ Res 65: 1283-1295.
  • Mizuno A, Baretti R, Buckberg GD, Young HH, Vinten-Johansen J, Ma XL, Ignarro LJ (1997) Endothelial stunning and myocyte recovery after reperfusion of jeopardized muscle: a role of l-arginine blood cardioplegia. J Thorac Cardiovasc Surg 113: 379-389.
  • Nagata H, Horiguchi T, Enzan K, Nishikawa T, Suzuki K (2005) Inhibition of poly (ADP-ribose) synthetase improves pulmonary arterial endothelium-dependent relaxation after ischemic-reperfusion injury of splanchnic artery in rats. Anesth Analg 101: 1799-1804.
  • Pacher P, Vaslin A, Benko R, Mabley JG, Liaudet L, Hasko G, Marton A, Batkai S, Kollai M, Szabo C (2004) A new, potent poly(ADP-ribose) polymerase inhibitor improves cardiac and vascular dysfunction associated with advanced aging. J Pharmacol Exp Ther 311: 485-491.
  • Sack FU, Lange R, Mehmanesh H, Amman K, Schnabel P, Zimmermann R, Dengler T, Otto HF, Hagl S (1997) Transferral of extrathoracic donor neoplasm by the cardiac allograft. J Heart Lung Transplant 16: 298-301.
  • Sims JL, Berger SJ, Berger NA (1983) Poly(ADP-ribose) polymerase inhibitors preserve nicotinamide adenine dinucleotide and adenosine 5'-triphosphate pools in DNA-damaged cells: mechanism of stimulation of unscheduled DNA synthesis. Biochemistry 22: 5188-5194.
  • Soriano FG, Pacher P, Mabley J, Liaudet L, Szabo C (2001) Rapid reversal of the diabetic endothelial dysfunction by pharmacological inhibition of poly(ADP-ribose) polymerase. Circ Res 89: 684-691.
  • Szabados E, Literati-Nagy P, Farkas B, Sumegi B (2000) BGP-15, a nicotinic amidoxime derivate protecting heart from ischemia reperfusion injury through modulation of poly(ADP-ribose) polymerase. Biochem Pharmacol 59: 937-945.
  • Szabo C, Zingarelli B, Salzman AL (1996) Role of poly-ADP ribosyltransferase activation in the vascular contractile and energetic failure elicited by exogenous and endogenous nitric oxide and peroxynitrite. Circ Res 78: 1051-1063.
  • Szabo G, Bahrle S, Batkai S, Stumpf N, Dengler TJ, Zimmermann R, Vahl CF, Hagl S (1998a) l-Arginine: effect on reperfusion injury after heart transplantation. World J Surg 22: 791-797.
  • Szabo G, Fazekas L, Bahrle S, MacDonald D, Stumpf N, Vahl CF, Hagl S (1998b) Endothelin-A and -B antagonists protect myocardial and endothelial function after ischemia/reperfusion in a rat heart transplantation model. Cardiovasc Res 39: 683-690.
  • Szabo G, Bahrle S, Stumpf N, Sonnenberg K, Szabo EE, Pacher P, Csont T, Schulz R, Dengler TJ, Liaudet L, Jagtap PG, Southan GJ, Vahl CF, Hagl S, Szabo C (2002) Poly(ADP-Ribose) polymerase inhibition reduces reperfusion injury after heart transplantation. Circ Res 90: 100-106.
  • Szabo G, Liaudet L, Hagl S, Szabo C (2004a) Poly(ADP-ribose) polymerase activation in the reperfused myocardium. Cardiovasc Res 61: 471-480.
  • Szabo G, Soos P, Bahrle S, Zsengeller Z, Flechtenmacher C, Hagl S, Szabo C (2004b) Role of poly(ADP-ribose) polymerase activation in the pathogenesis of cardiopulmonary dysfunction in a canine model of cardiopulmonary bypass. Eur J Cardiothorac Surg 25: 825-832.
  • Tanuma SI, Enomoto T, Yamada MA (1978) Changes in the level of poly ADP-ribosylation during a cell cycle. Exp Cell Res 117: 421-430.
  • Thiemermann C, Bowes J, Myint FP, Vane JR (1997) Inhibition of the activity of poly(ADP ribose) synthetase reduces ischemia-reperfusion injury in the heart and skeletal muscle. Proc Natl Acad Sci USA 94: 679-683.
  • Virag L (2005) Structure and function of poly(ADP-ribose) polymerase-1: role in oxidative stress-related pathologies. Curr Vasc Pharmacol 3: 209-214.
  • Virag L, Szabo C (2002) The therapeutic potential of poly(ADP-ribose) polymerase inhibitors. Pharmacol Rev 54: 375-429.
  • Weyrich AS, Ma XY, Lefer DJ, Albertine KH, Lefer AM (1993) In vivo neutralization of P-selectin protects feline heart and endothelium in myocardial ischemia and reperfusion injury. J Clin Invest 91: 2620-2629.
  • Yamazaki K, Miwa S, Ueda K, Tanaka S, Toyokuni S, Unimonh O, Nishimura K, Komeda M (2004) Prevention of myocardial reperfusion injury by poly(ADP-ribose) synthetase inhibitor, 3-aminobenzamide, in cardioplegic solution: in vitro study of isolated rat heart model. Eur J Cardiothorac Surg 26: 270-275.
Document Type
Publication order reference
Identifiers
YADDA identifier
bwmeta1.element.bwnjournal-article-abpv54p199kz
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.