Trends in Cardiovascular Medicine
Volume 16, Issue 8 , Pages 259-265 , November 2006

Bioactivation of Nitroglycerin by the Mitochondrial Aldehyde Dehydrogenase

  • Zhiqiang Chen
    • ,
  • Jonathan S. Stamler

      Affiliations

    • Corresponding Author InformationAddress correspondence to: Dr. Jonathan S. Stamler, Department of Medicine, Box 2612, Duke University Medical Center, Durham, NC 27710, USA. Tel.: (+1) 919-684-6933; fax: (+1) 919-684-6998.

References 

  1. Baxter K, Howden BO, Jablonski P. Heart preservation with Celsior solution improved by the addition of nitroglycerine. Transplantation. 2001;71:1380–1384
  2. Bennett BM, McDonald BJ, Nigam R. Biotransformation of organic nitrates and vascular smooth muscle cell function. Trends Pharmacol Sci. 1994;15:245–249
  3. Brudvig GW, Stevens TH, Chan SI. Reactions of nitric oxide with cytochrome c oxidase. Biochemistry. 1980;19:5275–5285
  4. Chen Z, Zhang J, Stamler JS. Identification of the enzymatic mechanism of nitroglycerin bioactivation. Proc Natl Acad Sci U S A. 2002;99:8306–8311
  5. Chen Z, Foster MW, Zhang J, et al. An essential role for mitochondrial aldehyde dehydrogenase in nitroglycerin bioactivation. Proc Natl Acad Sci U S A. 2005;102:12159–12164
  6. Csont T, Ferdinandy P. Cardioprotective effects of glyceryl trinitrate: Beyond vascular nitrate tolerance. Pharmacol Ther. 2005;105:57–68
  7. Daiber A, Oelze M, Coldewey M, et al. Oxidative stress and mitochondrial aldehyde dehydrogenase activity: A comparison of pentaerythritol tetranitrate with other organic nitrates. Mol Pharmacol. 2004;66:1372–1382
  8. Daiber A, Oelze M, Sulyok S, et al. Heterozygous deficiency of manganese superoxide dismutase in mice (Mn-SOD+/−): A novel approach to assess the role of oxidative stress for the development of nitrate tolerance. Mol Pharmacol. 2005;68:579–588
  9. Death AK, Nakhla S, McGrath KC, et al. Nitroglycerin upregulates matrix metalloproteinase expression by human macrophages. J Am Coll Cardiol. 2002;39:1943–1950
  10. De la Lande IS, Stepien JM, Philpott AC, et al. Aldehyde dehydrogenase, nitric oxide synthase and superoxide in ex vivo nitrate tolerance in rat aorta. Eur J Pharmacol. 2004;496:141–149
  11. DeMaster EG, Shirota FN, Nagasawa HT. The metabolic activation of cyanamide to an inhibitor of aldehyde dehydrogenase is catalyzed by catalase. Biochem Biophys Res Commun. 1984;122:358–365
  12. DeMaster EG, Redfern B, Quast BJ, et al. Mechanism for the inhibition of aldehyde dehydrogenase by nitric oxide. Alcohol. 1997;14:181–189
  13. DiFabio J, Ji Y, Vasiliou V, et al. Role of mitochondrial aldehyde dehydrogenase in nitrate tolerance. Mol Pharmacol. 2003;64:1109–1116
  14. Feldman RI, Weiner H. Horse liver aldehyde dehydrogenase: II. Kinetics and mechanistic implications of the dehydrogenase and esterase activity. J Biol Chem. 1972;247:267–272
  15. Fung HL. Biochemical mechanism of nitroglycerin action and tolerance: Is this old mystery solved?. Annu Rev Pharmacol Toxicol. 2004;44:67–85
  16. Gori T, Parker JD. The puzzle of nitrate tolerance: Pieces smaller than we thought?. Circulation. 2002;106:2404–2408
  17. Haefeli WE, Srivastava N, Kelsey KT, et al. Glutathione S-transferase polymorphism does not explain variation in nitroglycerin responsiveness. Clin Pharmacol Ther. 1993;53:463–468
  18. Hashimoto S, Kobayashi A. Clinical pharmacokinetics and pharmacodynamics of glyceryl trinitrate and its metabolites. Clin Pharmacokinet. 2003;42:205–221
  19. Higa M, Takasu N, Tamanaha T, et al. Nitroglycerin spray rapidly improves pain in a patient with chronic painful diabetic neuropathy. Diabet Med. 2004;21:1053–1054
  20. Ignarro LJ. After 130 years, the molecular mechanism of action of nitroglycerin is revealed. Proc Natl Acad Sci U S A. 2002;99:7816–7817
  21. Ignarro LJ, Lippton H, Edwards JC, et al. Mechanism of vascular smooth muscle relaxation by organic nitrates, nitrites, nitroprusside and nitric oxide: Evidence for the involvement of S-nitrosothiols as active intermediates. J Pharmacol Exp Ther. 1981;218:739–749
  22. Kollau A, Hofer A, Russwurm M, et al. Contribution of aldehyde dehydrogenase to mitochondrial bioactivation of nitroglycerin: Evidence for the activation of purified soluble guanylate cyclase through direct formation of nitric oxide. Biochem J. 2005;385:769–777
  23. Kozlov AV, Staniek K, Nohl H. Nitrite reductase activity is a novel function of mammalian mitochondria. FEBS Lett. 1999;454:127–130
  24. Larson HN, Weiner H, Hurley TD. Disruption of the coenzyme binding site and dimer interface revealed in the crystal structure of mitochondrial aldehyde dehydrogenase “Asian” variant. J Biol Chem. 2005;280:30550–30556
  25. Lauretti GR, Perez MV, Reis MP, et al. Double-blind evaluation of transdermal nitroglycerine as adjuvant to oral morphine for cancer pain management. J Clin Anesth. 2002;14:83–86
  26. Leesar MA, Stoddard MF, Dawn B, et al. Delayed preconditioning-mimetic action of nitroglycerin in patients undergoing coronary angioplasty. Circulation. 2001;103:2935–2941
  27. Li Y, Zhang D, Jin W, et al. Mitochondrial aldehyde dehydrogenase-2 (ALDH2) Glu504Lys polymorphism contributes to the variation in efficacy of sublingual nitroglycerin. J Clin Invest. 2006;116:506–511
  28. Lindsey I, Jones OM, Cunningham C, et al. Chronic anal fissure. Br J Surg. 2004;91:270–279
  29. Loehe F, Preissler G, Annecke T, et al. Continuous infusion of nitroglycerin improves pulmonary graft function of non-heart-beating donor lungs. Transplantation. 2004;77:1803–1808
  30. Mackenzie IS, Maki-Petaja KM, McEniery CM, et al. Aldehyde dehydrogenase 2 plays a role in the bioactivation of nitroglycerin in humans. Arterioscler Thromb Vasc Biol. 2005;25:1891–1895
  31. Mayer B. Bioactivation of nitroglycerin—a new piece in the puzzle. Angew Chem. 2003;42:388–391
  32. Moon KH, Kim BJ, Song BJ. Inhibition of mitochondrial aldehyde dehydrogenase by nitric oxide-mediated S-nitrosylation. FEBS Lett. 2005;579:6115–6120
  33. Mukerjee N, Pietruszko R. Inactivation of human aldehyde dehydrogenase by isosorbide dinitrate. J Biol Chem. 1994;269:21664–21669
  34. Munzel T, Daiber A, Mulsch A. Explaining the phenomenon of nitrate tolerance. Circ Res. 2005;97:618–628
  35. Murad F, Mittal CK, Arnold WP, et al. Guanylate cyclase: Activation by azide, nitro compounds, nitric oxide, and hydroxyl radical and inhibition by hemoglobin and myoglobin. Adv Cyclic Nucleotide Res. 1978;9:145–158
  36. Murphy TC, Arntzen R, Picklo MJ. Nitrate-based vasodilators inhibit multiple vascular aldehyde dehydrogenases. Cardiovasc Toxicol. 2005;5:321–332
  37. Nakamura Y, Moss AJ, Brown MW, et al. Long-term nitrate use may be deleterious in ischemic heart disease: A study using the databases from two large-scale postinfarction studies. Am Heart J. 1999;138:577–585
  38. Needleman P, Hunter FE. Effects of organic nitrates on mitochondrial respiration and swelling: Possible correlations with the mechanism of pharmacologic action. Mol Pharmacol. 1966;2:134–143
  39. Nunez C, Victor VM, Tur R. Discrepancies between nitroglycerin and NO-releasing drugs on mitochondrial oxygen consumption, vasoactivity, and the release of NO. Circ Res. 2005;97:1063–1069
  40. Pietruszko R, Mukerjee N, Blatter EE, et al. Nitrate esters as inhibitors and substrates of aldehyde dehydrogenase. Adv Exp Med Biol. 1995;372:25–34
  41. Shen ML, Lipsky JJ, Naylor S. Role of disulfiram in the in vitro inhibition of rat liver mitochondrial aldehyde dehydrogenase. Biochem Pharmacol. 2000;60:947–953
  42. Sydow K, Daiber A, Oelze M, et al. Central role of mitochondrial aldehyde dehydrogenase and reactive oxygen species in nitroglycerin tolerance and cross-tolerance. J Clin Invest. 2004;113:482–489
  43. Thatcher GR, Nicolescu AC, Bennettm BM, et al. Nitrates and NO release: Contemporary aspects in biological and medicinal chemistry. Free Radic Biol Med. 2004;37:1122–1143
  44. Towell J, Garthwaite T, Wang R. Erythrocyte aldehyde dehydrogenase and disulfiram-like side effects of hypoglycemics and antianginals. Alcohol Clin Exp Res. 1985;9:438–442
  45. Vallari RC, Pietruszko R. Human aldehyde dehydrogenase: Mechanism of inhibition of disulfiram. Science. 1982;216:637–639
  46. Yasuda H, Yamada M, Nakayama K, et al. Randomized phase II trial comparing nitroglycerin plus vinorelbine and cisplatin with vinorelbine and cisplatin alone in previously untreated stage IIIB/IV non-small-cell lung cancer. J Clin Oncol. 2006;24:688–694
  47. Zaher C, Goldberg GA, Kadlubek P. Estimating angina prevalence in a managed care population. Am J Manag Care. 2004;10:S339–S346
  48. Zhang J, Chen Z, Cobb FR, et al. Role of mitochondrial aldehyde dehydrogenase in nitroglycerin-induced vasodilation of coronary and systemic vessels: An intact canine model. Circulation. 2004;110:750–755
  49. Zhong L, Arner ES, Holmgren A. Structure and mechanism of mammalian thioredoxin reductase: The active site is a redox-active selenolthiol/selenenylsulfide formed from the conserved cysteine–selenocysteine sequence. Proc Natl Acad Sci U S A. 2000;97:5854–5859

PII: S1050-1738(06)00077-6

doi: 10.1016/j.tcm.2006.05.001

Trends in Cardiovascular Medicine
Volume 16, Issue 8 , Pages 259-265 , November 2006

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