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. 1995 May 15;308(Pt 1):231–236. doi: 10.1042/bj3080231

Ethanol potentiates interleukin-1 beta-stimulated inducible nitric oxide synthase expression in cultured vascular smooth muscle cells.

W Durante 1, K Cheng 1, R K Sunahara 1, A I Schafer 1
PMCID: PMC1136867  PMID: 7538755

Abstract

Experiments were performed to examine the effect of ethanol on the production of nitric oxide from interleukin-1 beta (IL-1 beta)-treated cultured rat aortic smooth muscle cells. Incubation of vascular smooth muscle cells with IL-1 beta resulted in the release of nitrite and in the intracellular accumulation of L-citrulline. In parallel with this, IL-1 beta increased inducible nitric oxide synthase (iNOS) mRNA and protein. Ethanol (6.5-650 mM) potentiated the IL-1 beta-mediated stimulation of iNOS mRNA production, the appearance of iNOS protein and the generation of nitrite and L-citrulline from smooth muscle cells in a concentration-dependent manner. In the absence of IL-1 beta, ethanol failed to induce iNOS expression. These results demonstrate that pharmacologically relevant concentrations of ethanol enhance the IL-1 beta-induced expression of the iNOS gene in vascular smooth muscle. The ability of ethanol to augment the release of the platelet inhibitor and vasodilator nitric oxide may, in part, contribute to the beneficial cardiovascular effects associated with moderate alcohol consumption.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beasley D., Schwartz J. H., Brenner B. M. Interleukin 1 induces prolonged L-arginine-dependent cyclic guanosine monophosphate and nitrite production in rat vascular smooth muscle cells. J Clin Invest. 1991 Feb;87(2):602–608. doi: 10.1172/JCI115036. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Busse R., Mülsch A. Induction of nitric oxide synthase by cytokines in vascular smooth muscle cells. FEBS Lett. 1990 Nov 26;275(1-2):87–90. doi: 10.1016/0014-5793(90)81445-t. [DOI] [PubMed] [Google Scholar]
  3. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  4. Cigarroa R. G., Lange R. A., Popma J. J., Yurow G., Sills M. N., Firth B. G., Hillis L. D. Ethanol-induced coronary vasodilation in patients with and without coronary artery disease. Am Heart J. 1990 Feb;119(2 Pt 1):254–259. doi: 10.1016/s0002-8703(05)80013-4. [DOI] [PubMed] [Google Scholar]
  5. Criqui M. H., Cowan L. D., Tyroler H. A., Bangdiwala S., Heiss G., Wallace R. B., Cohn R. Lipoproteins as mediators for the effects of alcohol consumption and cigarette smoking on cardiovascular mortality: results form the Lipid Research Clinics Follow-up Study. Am J Epidemiol. 1987 Oct;126(4):629–637. doi: 10.1093/oxfordjournals.aje.a114702. [DOI] [PubMed] [Google Scholar]
  6. Davis J. W., Phillips P. E. The effect of ethanol on human platelet aggregation in vitro. Atherosclerosis. 1970 May-Jun;11(3):473–477. doi: 10.1016/0021-9150(70)90025-0. [DOI] [PubMed] [Google Scholar]
  7. Deykin D., Janson P., McMahon L. Ethanol potentiation of aspirin-induced prolongation of the bleeding time. N Engl J Med. 1982 Apr 8;306(14):852–854. doi: 10.1056/NEJM198204083061406. [DOI] [PubMed] [Google Scholar]
  8. Durante W., Cheng K., Schafer A. I. Cyclic nucleotide regulation of interleukin-1 beta induced nitric oxide synthase expression in vascular smooth muscle cells. Thromb Res. 1994 Jul 1;75(1):63–71. doi: 10.1016/0049-3848(94)90140-6. [DOI] [PubMed] [Google Scholar]
  9. Durante W., Schini V. B., Catovsky S., Kroll M. H., Vanhoutte P. M., Schafer A. I. Plasmin potentiates induction of nitric oxide synthesis by interleukin-1 beta in vascular smooth muscle cells. Am J Physiol. 1993 Feb;264(2 Pt 2):H617–H624. doi: 10.1152/ajpheart.1993.264.2.H617. [DOI] [PubMed] [Google Scholar]
  10. Durante W., Schini V. B., Scott-Burden T., Junquero D. C., Kroll M. H., Vanhoutte P. M., Schafer A. I. Platelet inhibition by an L-arginine-derived substance released by IL-1 beta-treated vascular smooth muscle cells. Am J Physiol. 1991 Dec;261(6 Pt 2):H2024–H2030. doi: 10.1152/ajpheart.1991.261.6.H2024. [DOI] [PubMed] [Google Scholar]
  11. Gayer G. G., Gordon A., Miles M. F. Ethanol increases tyrosine hydroxylase gene expression in N1E-115 neuroblastoma cells. J Biol Chem. 1991 Nov 25;266(33):22279–22284. [PubMed] [Google Scholar]
  12. Gaziano J. M., Buring J. E., Breslow J. L., Goldhaber S. Z., Rosner B., VanDenburgh M., Willett W., Hennekens C. H. Moderate alcohol intake, increased levels of high-density lipoprotein and its subfractions, and decreased risk of myocardial infarction. N Engl J Med. 1993 Dec 16;329(25):1829–1834. doi: 10.1056/NEJM199312163292501. [DOI] [PubMed] [Google Scholar]
  13. Gilbert R. S., Herschman H. R. Transforming growth factor beta differentially modulates the inducible nitric oxide synthase gene in distinct cell types. Biochem Biophys Res Commun. 1993 Aug 31;195(1):380–384. doi: 10.1006/bbrc.1993.2054. [DOI] [PubMed] [Google Scholar]
  14. Goldberg R. J., Burchfiel C. M., Reed D. M., Wergowske G., Chiu D. A prospective study of the health effects of alcohol consumption in middle-aged and elderly men. The Honolulu Heart Program. Circulation. 1994 Feb;89(2):651–659. doi: 10.1161/01.cir.89.2.651. [DOI] [PubMed] [Google Scholar]
  15. Green L. C., Wagner D. A., Glogowski J., Skipper P. L., Wishnok J. S., Tannenbaum S. R. Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem. 1982 Oct;126(1):131–138. doi: 10.1016/0003-2697(82)90118-x. [DOI] [PubMed] [Google Scholar]
  16. Hibbs J. B., Jr, Westenfelder C., Taintor R., Vavrin Z., Kablitz C., Baranowski R. L., Ward J. H., Menlove R. L., McMurry M. P., Kushner J. P. Evidence for cytokine-inducible nitric oxide synthesis from L-arginine in patients receiving interleukin-2 therapy. J Clin Invest. 1992 Mar;89(3):867–877. doi: 10.1172/JCI115666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hoffman P. L., Tabakoff B. Ethanol and guanine nucleotide binding proteins: a selective interaction. FASEB J. 1990 Jun;4(9):2612–2622. doi: 10.1096/fasebj.4.9.2161371. [DOI] [PubMed] [Google Scholar]
  18. Imai T., Hirata Y., Kanno K., Marumo F. Induction of nitric oxide synthase by cyclic AMP in rat vascular smooth muscle cells. J Clin Invest. 1994 Feb;93(2):543–549. doi: 10.1172/JCI117005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. James M. J., Walsh J. A. Effects of aspirin and alcohol on platelet thromboxane synthesis and vascular prostacyclin synthesis. Thromb Res. 1985 Sep 1;39(5):587–593. doi: 10.1016/0049-3848(85)90238-5. [DOI] [PubMed] [Google Scholar]
  20. Keller J. W., Folts J. D. Relative effects of cigarette smoke and ethanol on acute platelet thrombus formation in stenosed canine coronary arteries. Cardiovasc Res. 1988 Jan;22(1):73–78. doi: 10.1093/cvr/22.1.73. [DOI] [PubMed] [Google Scholar]
  21. Klatsky A. L., Armstrong M. A., Friedman G. D. Risk of cardiovascular mortality in alcohol drinkers, ex-drinkers and nondrinkers. Am J Cardiol. 1990 Nov 15;66(17):1237–1242. doi: 10.1016/0002-9149(90)91107-h. [DOI] [PubMed] [Google Scholar]
  22. Koide M., Kawahara Y., Nakayama I., Tsuda T., Yokoyama M. Cyclic AMP-elevating agents induce an inducible type of nitric oxide synthase in cultured vascular smooth muscle cells. Synergism with the induction elicited by inflammatory cytokines. J Biol Chem. 1993 Nov 25;268(33):24959–24966. [PubMed] [Google Scholar]
  23. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  24. Landolfi R., Steiner M. Ethanol raises prostacyclin in vivo and in vitro. Blood. 1984 Sep;64(3):679–682. [PubMed] [Google Scholar]
  25. Langer R. D., Criqui M. H., Reed D. M. Lipoproteins and blood pressure as biological pathways for effect of moderate alcohol consumption on coronary heart disease. Circulation. 1992 Mar;85(3):910–915. doi: 10.1161/01.cir.85.3.910. [DOI] [PubMed] [Google Scholar]
  26. Marletta M. A., Yoon P. S., Iyengar R., Leaf C. D., Wishnok J. S. Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate. Biochemistry. 1988 Nov 29;27(24):8706–8711. doi: 10.1021/bi00424a003. [DOI] [PubMed] [Google Scholar]
  27. Mikhailidis D. P., Jenkins W. J., Barradas M. A., Jeremy J. Y., Dandona P. Platelet function defects in chronic alcoholism. Br Med J (Clin Res Ed) 1986 Sep 20;293(6549):715–718. doi: 10.1136/bmj.293.6549.715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Miles M. F., Diaz J. E., DeGuzman V. S. Mechanisms of neuronal adaptation to ethanol. Ethanol induces Hsc70 gene transcription in NG108-15 neuroblastoma x glioma cells. J Biol Chem. 1991 Feb 5;266(4):2409–2414. [PubMed] [Google Scholar]
  29. Moore R. D., Pearson T. A. Moderate alcohol consumption and coronary artery disease. A review. Medicine (Baltimore) 1986 Jul;65(4):242–267. doi: 10.1097/00005792-198607000-00004. [DOI] [PubMed] [Google Scholar]
  30. Mülsch A., Busse R. NG-nitro-L-arginine (N5-[imino(nitroamino)methyl]-L-ornithine) impairs endothelium-dependent dilations by inhibiting cytosolic nitric oxide synthesis from L-arginine. Naunyn Schmiedebergs Arch Pharmacol. 1990 Jan-Feb;341(1-2):143–147. doi: 10.1007/BF00195071. [DOI] [PubMed] [Google Scholar]
  31. Nathan C. Nitric oxide as a secretory product of mammalian cells. FASEB J. 1992 Sep;6(12):3051–3064. [PubMed] [Google Scholar]
  32. Nunokawa Y., Ishida N., Tanaka S. Cloning of inducible nitric oxide synthase in rat vascular smooth muscle cells. Biochem Biophys Res Commun. 1993 Feb 26;191(1):89–94. doi: 10.1006/bbrc.1993.1188. [DOI] [PubMed] [Google Scholar]
  33. Palmer R. M., Ferrige A. G., Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11;327(6122):524–526. doi: 10.1038/327524a0. [DOI] [PubMed] [Google Scholar]
  34. Radomski M. W., Palmer R. M., Moncada S. Comparative pharmacology of endothelium-derived relaxing factor, nitric oxide and prostacyclin in platelets. Br J Pharmacol. 1987 Sep;92(1):181–187. doi: 10.1111/j.1476-5381.1987.tb11310.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Rand M. L., Groves H. M., Packham M. A., Mustard J. F., Kinlough-Rathbone R. L. Inhibition by ethanol of thrombus formation induced by indwelling aortic catheters in rabbits. Thromb Haemost. 1991 Apr 8;65(4):454–455. [PubMed] [Google Scholar]
  36. Rimm E. B., Giovannucci E. L., Willett W. C., Colditz G. A., Ascherio A., Rosner B., Stampfer M. J. Prospective study of alcohol consumption and risk of coronary disease in men. Lancet. 1991 Aug 24;338(8765):464–468. doi: 10.1016/0140-6736(91)90542-w. [DOI] [PubMed] [Google Scholar]
  37. Rubin R., Rand M. L. Alcohol and platelet function. Alcohol Clin Exp Res. 1994 Feb;18(1):105–110. doi: 10.1111/j.1530-0277.1994.tb00888.x. [DOI] [PubMed] [Google Scholar]
  38. Schini V. B., Durante W., Elizondo E., Scott-Burden T., Junquero D. C., Schafer A. I., Vanhoutte P. M. The induction of nitric oxide synthase activity is inhibited by TGF-beta 1, PDGFAB and PDGFBB in vascular smooth muscle cells. Eur J Pharmacol. 1992 Jun 17;216(3):379–383. doi: 10.1016/0014-2999(92)90434-6. [DOI] [PubMed] [Google Scholar]
  39. Schini V. B., Junquero D. C., Scott-Burden T., Vanhoutte P. M. Interleukin-1 beta induces the production of an L-arginine-derived relaxing factor from cultured smooth muscle cells from rat aorta. Biochem Biophys Res Commun. 1991 Apr 15;176(1):114–121. doi: 10.1016/0006-291x(91)90897-g. [DOI] [PubMed] [Google Scholar]
  40. Scott-Burden T., Resink T. J., Baur U., Bürgin M., Bühler F. R. Epidermal growth factor responsiveness in smooth muscle cells from hypertensive and normotensive rats. Hypertension. 1989 Apr;13(4):295–304. doi: 10.1161/01.hyp.13.4.295. [DOI] [PubMed] [Google Scholar]
  41. Spolarics Z., Spitzer J. J., Wang J. F., Xie J., Kolls J., Greenberg S. Alcohol administration attenuates LPS-induced expression of inducible nitric oxide synthase in Kupffer and hepatic endothelial cells. Biochem Biophys Res Commun. 1993 Dec 15;197(2):606–611. doi: 10.1006/bbrc.1993.2522. [DOI] [PubMed] [Google Scholar]
  42. Szabo G., Puppolo M., Verma B., Catalano D. Regulatory potential of ethanol and retinoic acid on human monocyte functions. Alcohol Clin Exp Res. 1994 Jun;18(3):548–554. doi: 10.1111/j.1530-0277.1994.tb00908.x. [DOI] [PubMed] [Google Scholar]
  43. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Van Haastert P. J., Van Driel R., Jastorff B., Baraniak J., Stec W. J., De Wit R. J. Competitive cAMP antagonists for cAMP-receptor proteins. J Biol Chem. 1984 Aug 25;259(16):10020–10024. [PubMed] [Google Scholar]
  45. Verbeuren T. J., Bonhomme E., Laubie M., Simonet S. Evidence for induction of nonendothelial NO synthase in aortas of cholesterol-fed rabbits. J Cardiovasc Pharmacol. 1993 May;21(5):841–845. doi: 10.1097/00005344-199305000-00023. [DOI] [PubMed] [Google Scholar]
  46. Vodovotz Y., Bogdan C., Paik J., Xie Q. W., Nathan C. Mechanisms of suppression of macrophage nitric oxide release by transforming growth factor beta. J Exp Med. 1993 Aug 1;178(2):605–613. doi: 10.1084/jem.178.2.605. [DOI] [PMC free article] [PubMed] [Google Scholar]

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