YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Effects of 2-Chloro-3-( 4-cyanophenylamino )-1,4-naphthoquinone( NQ-Y15 ) on Normal and Ischemical/reperfused Rat Hearts

정상 및 허혈/재관류 흰쥐 심장에 대한 2-클로로-3-(4-시아노페닐아미노 )-1,4-나프토퀴논 ( NQ-Y15 )의 작용

  • Moon, Chang-Hyun (Department of Physiology, School of Medicine, Ajou University) ;
  • Kim, Ji-Young (Department of Physiology, School of Medicine, Ajou University) ;
  • Baik, Eun-Joo (Department of Physiology, School of Medicine, Ajou University) ;
  • Lee, Soo-Hwan (Department of Physiology, School of Medicine, Ajou University) ;
  • Ryu, Chung-Kyu (College of Pharmacy, Ehwa Women's University)
  • 문창현 (아주대학교 의과대학 생리학교실) ;
  • 김지영 (아주대학교 의과대학 생리학교실) ;
  • 백은주 (아주대학교 의과대학 생리학교실) ;
  • 이수환 (아주대학교 의과대학 생리학교실) ;
  • 류충규 (이화여자대학교 약학대학)
  • Published : 1997.12.01
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Abstract

Studies on the effect of quinones on cardiac function has been conducted with normal hearts. But not with injured hearts, I.e. ischemia/reperfusion-injured heart. Quinone compounds are known to produce oxygen free radicals during metabolism, and for this reason, quinones are implicated in the aggravation of ischemia/reperfusion injury or cardioprotection, as in the case of ischemic preconditioning depending on the experimental conditions. The present study was carried out to examine the effect of 2-chloro-3-(4-cyanophenylamino)-1.4-naphthoquinone (NQ-Y15) on cardiac function of ischemic/reperfused and normal rat hearts. In isolated perfused hearts, various functional parameters such as left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (EDP) and maximum positive and negative dP/dt ($[\pm}dP/dt_{max}$), time to contracture, heart rate (HR) and coronary flow rate (CFR) were measured before and 30 min after dosing and following 25 min ischemia/30min reperfusion. NQ-Y15 increased LVDP, +dP/$d_{max}$and -dP/$dt_{min}$ by 18%. 30%, and 40%, respectively. There were no significant changes in other haemodynamic parameters. After ischemia/reperfusion injury, pretreatment with NQ-Y15 induced a significant decrease in LVDP and $[\pm}dP/dt_{max}$, but an increase in EDP. LDH-release was not significantly increased. These results suggested that NQ-Y15 may augment the ventricular contractility but it makes hearts more vulnerable to ischemia/reperfusion injury.

Keywords

References

  1. Cirs. Res. v.61 Proarrhythmic effects of an oxygen-derived free radical generating system on action potentials recorded from arrhythmias Pallandi R. R.;Perry, M. A.;Campbell T. J.
  2. J. Mol. Cell. Cardiol. v.29 Free radicals and calcium: simultaneous interacting triggers as determinants of vulnerability to reperfusion-induced arrhythmias in thr rat heart Hearse D. J.;Tasaki A.
  3. Am. J. Physiol. v.251 Four brief periods of myocardial ischemia cause no cumulative ATP loss or necrosis Reimer K. A.;Murrey C. E.;Yamasawa I.;Hill M. L.;Jenning R.B.
  4. Circ. Res. v.80 Oxygen radicals can induce preconditioning in rabbit hearts Isabella T.;Davide D.;Nicola E.;Annalisa S.;Ciro D. S.;Anna V.;Annamaria E.;Massino C.;Giuseppe A.
  5. Cardiovasc. Res. v.28 Superoxide dismutase and N-2-mercaptopropionyl glycine attenuate infarct size limitation effect of ischaemic preconditioning in the rabbit Tanaka M.;Fujiwara H.;Yamasaki K.;Sasayama S.
  6. Biochem. Pharmacol. v.54 Thromboxane A₂synthase inhibition and thromboxane A₂receptor blockade by 2-[(4-cyanophenyl)amino]-3-1,4-naphthalenedione (NQ-Y15) in rat platelets Chang T. S.;Kim H. M.;Lee K. S.;Khil L. Y.;Mar W. C.;Ryu C. K.;Moon C. K.
  7. J. Mol. Cell. Cardiol. v.32 Ischemia-induced and reperfusion-induced arrhythmias differ in their sensitivity to potassium : implication for mechanisms of initiation and maintenance of ventricular fibrillation Curtis M. J.;Hearse D. J.
  8. J. Pharmacol. Exp. Ther. v.287 Mechanisms of plumbagin action on guinea pig isolated atria Floreani M.;Forlin A.;Pandolfo L.;Petrone M.;Bellin S.
  9. J. Pharmacol. Exp. Ther. v.260 Catecholamine-mediated positive inotropic effect of simple quinones is related to superoxide anion generation Floreani M.;Carpenedo F.
  10. Naunyn Schmiedebergs Arch. Pharmacol. v.339 Effects of 2-methyl-1,4-napthoquinone (menadione) on myocardial contractility and cardiac sarcoplasmic reticulum Ca-ATPase Floreani M.;Santi-Soncin E.;Carpenedo F.
  11. Gen. Pharmacol. v.26 Metabolism of simple quinones in guinea pig and rat cardiac tissue Floreani, M.;Carpenedo, F.
  12. J. Biol. Chem. v.266 Significance of the "Rieske" iron-sul fur protein for formation and function of the ubiquinol-oxidation pocket of mitochondrial cytochrome C reductase (bc1 complex) Brandt U.;Haase U.;Schagger H.;von-Jagow, G.
  13. Biochim. Biophys. Acta v.172 One electron transfer reactions in biochemical systems Ⅲ. One electron reduction of quinones by microsomal flavin enzymes Iwanagi T.;Yamazaki I
  14. Biochim. Biophys. Acta v.216 One-electron-transfer reactions in biochemical systems. V. Difference in the mechanism of quinone reduction by the NADH dehydrogenase and the NAD(P)H dehydrogenase (DT-diaphorase) Iyanagi T.;Yamazaki I.
  15. Biochem. Pharmacol. v.29 Relationship of the single-electron reduction potential of quinones to their reduction by flavoproteins Powis G.;Appel P. L.
  16. Mol. Pharmacol. v.20 Quinone-stimulated superoxide formation by subcellular fractions, isolated hepatocytes and other cells Powis G.;Svingen B. A.;Appel P. L.
  17. Free radicals in biology v.5 Free Radical Intermediates in the metabolism of toxic chemicals Mason R. P.;Pryor W. A.(ed.)
  18. Free Rad. Biol. Med. v.5 Effect of superoxide dismutase on the autoxidation of various hydroquinones. A possible role of superoxide dismutase as a superoxide:semiquinone oxidoreductase Ernster L.
  19. Biochem. J. v.256 DT-diaphorase-catalysed reduction of 1,4-naphthoquinone derivatives and glutathionyl quinone conjugates Buffinton, G.;Ollinger K.;Brunmark A.;Cadenas E.
  20. N. Engl. J. Med. v.312 Oxygen-derived free radicals in postischemic tissue injury McCord, J.M.
  21. Am. J. Physiol. v.266 In vivo monitoring of norepinehrine and OH generation on myocardial ischemic injury by dialysis technique Toshio O.;Hiroshi H.;Yasumitsu Y.
  22. J. Clin. Invest. v.65 Protection from oxygen toxicity with endotoxin : role of endogenous antioxidant enzyme of the lung Frank L. S.;Massaro D.
  23. Am. J. Physiol. v.269 Myocardial adaptation to ischemia by oxidative stress induced by endotoxin Nilanjana M.;Masazumi W.;Daniel E.;Richard M. E.;Valerian E. K.;Elena K.;Vladimir T.;Geraqld A. C.;Dipak KD
  24. J. Clin. Invest. v.79 Recombinant tumor necrosis factor/cachectin and interleukin-1 pretreatment decreases lung oxidized glutathione accumulation, lung injury and mortality in rats exposed to hyperoxia White C. W.;Ghezzi p.;dinarello C. A.;Caldwell S. A.;McMurtry U.;Repine J. E.
  25. Am. J. Med. v.91 no.SUP.3C Oxidant-antioxidant balance : some observations from studies of ischemia-reperfusion in isolated perfused rat hearts John E. R.
  26. Can. J. Physiol. Pharmacol. v.69 Ischemic and reperfusion injury in the heart. Cellular mechanisms and pharmacological interventions Karmazyn M.
  27. Biochem. Pharmacol. v.48 Role of thiol homeostasis and adenine nucleotide metabolism in the protective effects of fructose in quinone-induced cytotoxicity in rat hepatocytes Corike T.;Ineke V. H.;Menno P. J.;De Winther;Diels. V. D.;Horach J. M.
  28. J. Pharmacol. Exp. Ther. v.256 Modifications of cardiac contractility by redox cycling alkylating and mixed redox cycling/alkylating quinones Floreani M.;Carpenedo F.