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. 1991 Aug;103(4):1905–1908. doi: 10.1111/j.1476-5381.1991.tb12350.x

Nitroglycerin relaxes coronary artery of the pig with no change in glutathione content or glutathione S-transferase activity.

M Sakanashi 1, T Matsuzaki 1, Y Aniya 1
PMCID: PMC1908217  PMID: 1912979

Abstract

1. The role of glutathione content and glutathione S-transferase activity in vascular relaxant responses to nitroglycerin was evaluated in potassium (30 mM)-contracted coronary artery strips of the pig by measuring changes in tension, glutathione content and glutathione S-transferase activity. 2. Prior exposure of coronary artery strips to nitroglycerin (10(-5)M or 10(-4)M for 20 min) resulted in tachyphylaxis to subsequent relaxation to nitroglycerin (10(-8)-10(-5)M). 3. The glutathione content and glutathione S-transferase activity of the arterial strips rendered tachyphylactic by prior exposure to nitroglycerin (10(-5)M for 20 min or 10(-3)M for 120 min) were not significantly different from those of control strips. 4. Treatment with diethyl maleate (10(-4)M or 10(-3)M for 60 min) markedly depleted arterial glutathione content in a concentration-dependent manner with no change in glutathione S-transferase activity. 5. The relaxant response of coronary artery strips to nitroglycerin (10(-8)-10(-5)M) was completely unaffected following treatment with diethyl maleate (10(-4)M or 10(-3)M for 60 min). 6. The results suggest that vascular glutathione content does not play an important role in vascular relaxation or tolerance development to nitroglycerin, at least in pig isolated coronary artery.

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Selected References

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  1. Boyland E., Chasseaud L. F. Enzyme-catalysed conjugations of glutathione with unsaturated compounds. Biochem J. 1967 Jul;104(1):95–102. doi: 10.1042/bj1040095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Boyland E., Chasseaud L. F. Enzymes catalysing conjugations of glutathione with alpha-beta-unsaturated carbonyl compounds. Biochem J. 1968 Oct;109(4):651–661. doi: 10.1042/bj1090651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Feelisch M., Noack E. A. Correlation between nitric oxide formation during degradation of organic nitrates and activation of guanylate cyclase. Eur J Pharmacol. 1987 Jul 2;139(1):19–30. doi: 10.1016/0014-2999(87)90493-6. [DOI] [PubMed] [Google Scholar]
  4. Gruetter C. A., Lemke S. M. Dissociation of cysteine and glutathione levels from nitroglycerin-induced relaxation. Eur J Pharmacol. 1985 Apr 23;111(1):85–95. doi: 10.1016/0014-2999(85)90116-5. [DOI] [PubMed] [Google Scholar]
  5. Habig W. H., Pabst M. J., Jakoby W. B. Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem. 1974 Nov 25;249(22):7130–7139. [PubMed] [Google Scholar]
  6. Ignarro L. J., Kadowitz P. J. The pharmacological and physiological role of cyclic GMP in vascular smooth muscle relaxation. Annu Rev Pharmacol Toxicol. 1985;25:171–191. doi: 10.1146/annurev.pa.25.040185.001131. [DOI] [PubMed] [Google Scholar]
  7. Ignarro L. J., Lippton H., Edwards J. C., Baricos W. H., Hyman A. L., Kadowitz P. J., Gruetter C. A. 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 Sep;218(3):739–749. [PubMed] [Google Scholar]
  8. Kukovetz W. R., Holzmann S. Mechanisms of nitrate-induced vasodilatation and tolerance on a biochemical base. Z Kardiol. 1985;74 (Suppl 1):39–44. [PubMed] [Google Scholar]
  9. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  10. Needleman P., Jakschik B., Johnson E. M., Jr Sulfhydryl requirement for relaxation of vascular smooth muscle. J Pharmacol Exp Ther. 1973 Nov;187(2):324–331. [PubMed] [Google Scholar]
  11. Needleman P., Johnson E. M., Jr Mechanism of tolerance development to organic nitrates. J Pharmacol Exp Ther. 1973 Mar;184(3):709–715. [PubMed] [Google Scholar]
  12. Packer M., Lee W. H., Kessler P. D., Gottlieb S. S., Medina N., Yushak M. Prevention and reversal of nitrate tolerance in patients with congestive heart failure. N Engl J Med. 1987 Sep 24;317(13):799–804. doi: 10.1056/NEJM198709243171304. [DOI] [PubMed] [Google Scholar]
  13. Reed D. J., Babson J. R., Beatty P. W., Brodie A. E., Ellis W. W., Potter D. W. High-performance liquid chromatography analysis of nanomole levels of glutathione, glutathione disulfide, and related thiols and disulfides. Anal Biochem. 1980 Jul 15;106(1):55–62. doi: 10.1016/0003-2697(80)90118-9. [DOI] [PubMed] [Google Scholar]
  14. Svendsen J. H., Klarlund K., Aldershvile J., Waldorff S. N-acetylcysteine modifies the acute effects of isosorbide-5-mononitrate in angina pectoris patients evaluated by exercise testing. J Cardiovasc Pharmacol. 1989 Feb;13(2):320–323. doi: 10.1097/00005344-198902000-00022. [DOI] [PubMed] [Google Scholar]
  15. Torresi J., Horowitz J. D., Dusting G. J. Prevention and reversal of tolerance to nitroglycerine with N-acetylcysteine. J Cardiovasc Pharmacol. 1985 Jul-Aug;7(4):777–783. doi: 10.1097/00005344-198507000-00024. [DOI] [PubMed] [Google Scholar]
  16. Winniford M. D., Kennedy P. L., Wells P. J., Hillis L. D. Potentiation of nitroglycerin-induced coronary dilatation by N-acetylcysteine. Circulation. 1986 Jan;73(1):138–142. doi: 10.1161/01.cir.73.1.138. [DOI] [PubMed] [Google Scholar]
  17. Yeates R. A., Schmid M., Leitold M. Antagonism of glycerol trinitrate activity by an inhibitor of glutathione S-transferase. Biochem Pharmacol. 1989 Jun 1;38(11):1749–1753. doi: 10.1016/0006-2952(89)90408-5. [DOI] [PubMed] [Google Scholar]

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