Journal of Physiology and Biochemistry

, Volume 70, Issue 2, pp 509–523 | Cite as

Acute ethanol intake induces mitogen-activated protein kinase activation, platelet-derived growth factor receptor phosphorylation, and oxidative stress in resistance arteries

  • Natália A. Gonzaga
  • Glaucia E. Callera
  • Alvaro Yogi
  • André S. Mecawi
  • José Antunes-Rodrigues
  • Regina H. Queiroz
  • Rhian M. Touyz
  • Carlos R. Tirapelli
Original Paper

Abstract

In the present study, we investigated the role of angiotensin type I (AT1) receptor in reactive oxygen species (ROS) generation and mitogen-activated protein kinases (MAPK) activation induced by acute ethanol intake in resistance arteries. We also evaluated the effect of ethanol on platelet-derived growth factor receptors (PDGF-R) phosphorylation and the role of this receptor on ROS generation by ethanol. Ethanol (1 g/kg; p.o. gavage) effects were assessed within 30 min in male Wistar rats. Acute ethanol intake did not alter angiotensin I or angiotensin II levels in the rat mesenteric arterial bed (MAB). Ethanol induced vascular oxidative stress, and this response was not prevented by losartan (10 mg/kg; p.o. gavage), a selective AT1 receptor antagonist. MAB from ethanol-treated rats displayed increased SAPK/JNK and PDGF-R phosphorylation, responses that were not prevented by losartan. The phosphorylation levels of protein kinase B (Akt) and eNOS were not affected by acute ethanol intake. MAB nitrate levels and the reactivity of this tissue to acetylcholine, phenylephrine, and sodium nitroprusside were not affected by ethanol intake. Ethanol did not alter plasma antioxidant capacity, the levels of reduced glutathione, or the activities of superoxide dismutase and catalase in the rat MAB. Short-term effects of ethanol (50 mmol/l) were evaluated in vascular smooth muscle cells (VSMC) isolated from rat MAB. Ethanol increased ROS generation, and this response was not affected by AG1296, a PDGF-R inhibitor, or losartan. Finally, ethanol did not alter MAPK or PDGF-R phosphorylation in cultured VSMC. Our study provides novel evidence that acute ethanol intake induces ROS generation, PDGF-R phosphorylation, and MAPK activation through AT(1)-independent mechanisms in resistance arteries in vivo. MAPK and PDGF-R play a role in vascular signaling and cardiovascular diseases and may contribute to the vascular pathobiology of ethanol.

Keywords

Ethanol Resistance arteries Superoxide anions Platelet-derived growth factor Mitogen-activated protein kinases 

References

  1. 1.
    Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126PubMedCrossRefGoogle Scholar
  2. 2.
    Adeagbo ASO, Triggle CR (1993) Varying extracellular [K+]: a functional approach to separating EDHF- and EDNO-related mechanisms in perfused rat mesenteric arterial bed. J Cardiovasc Pharmacol 21:423–429PubMedCrossRefGoogle Scholar
  3. 3.
    Aroor AR, Shukla SD (2004) MAP kinase signaling in diverse effects of ethanol. Life Sci 74(19):2339–2364PubMedCrossRefGoogle Scholar
  4. 4.
    Beulens JW, Rimm EB, Ascherio A, Spiegelman D, Hendriks HF, Mukamal KJ (2007) Alcohol consumption and risk for coronary heart disease among men with hypertension. Ann Intern Med 146(1):10–19PubMedCrossRefGoogle Scholar
  5. 5.
    Callera GE, Touyz RM, Tostes RC, Yogi A, He Y, Malkinson S, Schiffrin EL (2005) Aldosterone activates vascular p38MAP kinase and NADPH oxidase via c-Src. Hypertension 45:773–779PubMedCrossRefGoogle Scholar
  6. 6.
    Catarzi S, Biagioni C, Giannoni E, Favilli F, Marcucci T, Iantomasi T, Vincenzini MT (2005) Redox regulation of platelet-derived-growth-factor-receptor: role of NADPH-oxidase and c-Src tyrosine kinase. Biochim Biophys Acta 1745:166–175PubMedCrossRefGoogle Scholar
  7. 7.
    Chabielska E, Pietraszek M, Malinowska B, Buczko W (1988) The effect of ethanol on some serotonergic mechanisms in rat blood platelets. Pol J Pharmacol Pharm 40(3):241–249PubMedGoogle Scholar
  8. 8.
    Chen A, Davis BH (2000) The DNA binding protein BTEB mediates acetaldehyde-induced, jun N-terminal kinase-dependent alphaI(I) collagen gene expression in rat hepatic stellate cells. Mol Cell Biol 20(8):2818–2826PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Daigle C, Martens FM, Girardot D, Dao HH, Touyz RM, Moreau P (2004) Signaling of angiotensin II-induced vascular protein synthesis in conduit and resistance arteries in vivo. BMC Cardiovasc Disord 10(4)Google Scholar
  10. 10.
    Das SK, Mukherjee S, Gupta G, Rao DN, Vasudevan DM (2010) Protective effect of resveratrol and vitamin E against ethanol-induced oxidative damage in mice: biochemical and immunological basis. Indian J Biochem Biophys 47(1):32–37PubMedGoogle Scholar
  11. 11.
    Demori I, Voci A, Fugassa E, Burlando B (2006) Combined effects of high fat diet and ethanol induce oxidative stress in rat liver. Alcohol 40(3):185–191PubMedCrossRefGoogle Scholar
  12. 12.
    El-Mas MM, Abdel-Rahman A (1999) Acute hemodynamic effects of ethanol in conscious spontaneously hypertensive and normotensive rats. Alcohol Clin Exp Res 23(2):285–292PubMedCrossRefGoogle Scholar
  13. 13.
    El-Mas MM, Zhang J, Abdel-Rahman AA (2006) Upregulation of vascular inducible nitric oxide synthase mediates the hypotensive effect of ethanol in conscious female rats. J Appl Physiol 100(3):1011–1018PubMedCrossRefGoogle Scholar
  14. 14.
    Garland CJ, Plane F, Kemp BK, Cocks TM (1995) Endothelium-dependent hyperpolarization: a role in the control of vascular tone. Trends Pharmacol Sci 16:23–30PubMedCrossRefGoogle Scholar
  15. 15.
    Griendling KK, Sorescu D, Ushio-Fukai M (2000) NAD(P)H oxidase: role in cardiovascular biology and disease. Circ Res 86:494–501PubMedCrossRefGoogle Scholar
  16. 16.
    Haorah J, Knipe B, Leibhart J, Ghorpade A, Persidsky Y (2005) Alcohol-induced oxidative stress in brain endothelial cells causes blood–brain barrier dysfunction. J Leukoc Biol 78(6):1223–1232PubMedCrossRefGoogle Scholar
  17. 17.
    Haorah J, Floreani NA, Knipe B, Persidsky Y (2011) Stabilization of superoxide dismutase by acetyl-l-carnitine in human brain endothelium during alcohol exposure: novel protective approach. Free Radic Biol Med 51(8):1601–1609PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Heeneman S, Haendeler J, Saito Y, Ishida M, Berk BC (2000) Angiotensin II induces transactivation of two different populations of the PDGFß-receptor: key role for the adaptor protein Shc. J Biol Chem 275:15926–15932PubMedCrossRefGoogle Scholar
  19. 19.
    Husain K, Ferder L, Ansari RA, Lalla J (2011) Chronic ethanol ingestion induces aortic inflammation/oxidative endothelial injury and hypertension in rats. Hum Exp Toxicol 30(8):930–939PubMedCrossRefGoogle Scholar
  20. 20.
    Husain K, Vazquez M, Ansari RA, Malafa MP, Lalla J (2008) Chronic alcohol-induced oxidative endothelial injury relates to angiotensin II levels in the rat. Mol Cell Biochem 307(1–2):51–58PubMedGoogle Scholar
  21. 21.
    Husain K, Vazquez-Ortiz M, Lalla J (2007) Down regulation of aortic nitric oxide and antioxidant systems in chronic alcohol-induced hypertension in rats. Hum Exp Toxicol 26(5):427–434PubMedCrossRefGoogle Scholar
  22. 22.
    Izbeki F, Wittmann T, Csáti S, Jeszenszky E, Lonovics J (2001) Opposite effects of acute and chronic administration of alcohol on gastric emptying and small bowel transit in rat. Alcohol Alcohol 36(4):304–308PubMedCrossRefGoogle Scholar
  23. 23.
    Klatsky AL, Armstrong MA, Friedman GD (1992) Alcohol and mortality. Ann Intern Med 117:646–654PubMedCrossRefGoogle Scholar
  24. 24.
    Kono H, Rusyn I, Uesugi T, Yamashina S, Connor HD, Dikalova A, Mason RP, Thurman RG (2001) Diphenyleneiodonium sulfate, an NADPH oxidase inhibitor, prevents early alcohol-induced liver injury in the rat. Am J Physiol Gastrointest Liver Physiol 280(5):G1005–G1012PubMedGoogle Scholar
  25. 25.
    Lakshmanan AP, Harima M, Sukumaran V, Soetikno V, Thandavarayan RA, Suzuki K, Kodama M, Nagata M, Takagi R, Watanabe K (2012) Modulation of AT-1R/AMPK-MAPK cascade plays crucial role for the pathogenesis of diabetic cardiomyopathy in transgenic type 2 diabetic (spontaneous diabetic torii) rats. Biochem Pharmacol 83(5):653–660PubMedCrossRefGoogle Scholar
  26. 26.
    Lee YJ, Aroor AR, Shukla SD (2002) Temporal activation of p42/44 mitogen-activated protein kinase and c-Jun N-terminal kinase by acetaldehyde in rat hepatocytes and its loss after chronic ethanol exposure. J Pharmacol Exp Ther 301(3):908–914PubMedCrossRefGoogle Scholar
  27. 27.
    Linkola J, Fyhrquist F, Nieminen MM, Weber TH, Tontti K (1976) Renin-aldosterone axis in ethanol intoxication and hangover. Eur J Clin Investig 6(2):191–194CrossRefGoogle Scholar
  28. 28.
    Luo J, Miller MW (1999) Platelet-derived growth factor-mediated signal transduction underlying astrocyte proliferation: site of ethanol action. J Neurosci 19(22):10014–10025PubMedGoogle Scholar
  29. 29.
    Luo Z, Fujio Y, Kureishi Y, Rudic RD, Daumerie G, Fulton D, Sessa WC, Walsh K (2000) Acute modulation of endothelial Akt/PKB activity alters nitric oxide-dependent vasomotor activity in vivo. J Clin Investig 106:493–499PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Malinowska B, Pawlak D, Chabielska E, Buczko W (1989) Cardiovascular effects of ethanol in anaesthetized, conscious and pithed rats. Drug Alcohol Depend 24(1):51–56PubMedCrossRefGoogle Scholar
  31. 31.
    Mármol F, Sánchez J, López D, Martínez N, Roselló-Catafau J, Mitjavila MT, Puig-Parellada P (2007) Loss of adaptation to oxidative stress as a mechanism for aortic damage in aging rats. J Physiol Biochem 63(3):239–247PubMedCrossRefGoogle Scholar
  32. 32.
    Masamune A, Kikuta K, Satoh M, Satoh A, Shimosegawa T (2002) Alcohol activates activator protein-1 and mitogen-activated protein kinases in rat pancreatic stellate cells. J Pharmacol Exp Ther 302(1):36–42PubMedCrossRefGoogle Scholar
  33. 33.
    McCulloch AI, Bottrill FE, Randall MD, Hiley CR (1997) Characterization and modulation of EDHF-mediated relaxations in the rat isolated superior mesenteric arterial bed. Br J Pharmacol 120:1431–1438PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Murasawa S, Mori Y, Nozawa Y, Gotoh N, Shibuya M, Masaki H, Maruyama K, Tsutsumi Y, Moriguchi Y, Shibazaki Y, Tanaka Y, Iwasaka T, Inada M, Matsubara H (1998) Angiotensin II type 1 receptor–induced extracellular signal-regulated protein kinase activation is mediated by Ca2+/calmodulin-dependent transactivation of epidermal growth factor receptor. Circ Res 82:1338–1348PubMedCrossRefGoogle Scholar
  35. 35.
    Nanji AA, Khwaja S, Khettry U, Sadrzadeh SMH (1994) Plasma endothelin levels in chronic ethanol fed rats: relationship to pathologic liver injury. Life Sci 54:423–428PubMedCrossRefGoogle Scholar
  36. 36.
    Nguyen Dinh Cat A, Touyz RM (2011) A new look at the renin–angiotensin system—focusing on the vascular system. Peptides 32(10):2141–2150PubMedCrossRefGoogle Scholar
  37. 37.
    Nieminen MM, Fyhrquist F, Linkola J, Tikkanen I, Tontti K (1981) Renin–aldosterone axis in ethanol intoxication. Pharmacol Biochem Behav 15(6):879–882PubMedCrossRefGoogle Scholar
  38. 38.
    Rocha JT, Hipólito UV, Callera GE, Yogi A, Neto Filho M, Bendhack LM, Touyz RM, Tirapelli CR (2012) Ethanol induces vascular relaxation via redox-sensitive and nitric oxide-dependent pathways. Vasc Pharmacol 56(1–2):74–83CrossRefGoogle Scholar
  39. 39.
    Rocha JT, Hipólito UV, Martins-Oliveira A, Tirapelli DP, Batalhão ME, Carnio EC, Queiroz RH, Coelho EB, Cunha TM, Tanus-Santos JE, Tirapelli CR (2012) Ethanol consumption alters the expression and reactivity of adrenomedullin in the rat mesenteric arterial bed. Alcohol Alcohol 47(1):9–17PubMedCrossRefGoogle Scholar
  40. 40.
    Sachinidis A, Gouni-Berthold I, Seul C, Seewald S, Ko Y, Schmitz U, Vetter H (1999) Early intracellular signalling pathway of ethanol in vascular smooth muscle cells. Br J Pharmacol 128(8):1761–1771PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Schlorff EC, Husain K, Somani SM (1999) Dose- and time-dependent effects of ethanol on plasma antioxidant system in rat. Alcohol 17(2):97–105PubMedCrossRefGoogle Scholar
  42. 42.
    Skliros EA, Papadodima SA, Sotiropoulos A, Xipnitos C, Kollias A, Spiliopoulou CA (2012) Relationship between alcohol consumption and control of hypertension among elderly greeks. The Nemea Primary Care Study. Hell J Cardiol 53:26–32Google Scholar
  43. 43.
    Thakker KD (1998) An overview of health risks and benefits of alcohol consumption. Alcohol Clin Exp Res 22(7 Suppl):285S–298SPubMedCrossRefGoogle Scholar
  44. 44.
    Tharaux P-L, Chatziantoniou C, Fakhouri F, Dussaule J-C (2000) Angiotensin II activates collagen I through a mechanism involving the MAP/ER kinase pathway. Hypertension 36:330–336PubMedCrossRefGoogle Scholar
  45. 45.
    Thevananther S, Brecher AS (1994) Interaction of acetaldehyde with plasma proteins of the renin–angiotensin system. Alcohol 11(6):493–499PubMedCrossRefGoogle Scholar
  46. 46.
    Thun MJ, Peto R, Lopez AD, Monaco JH, Henley SJ, Heath CW, Doll R (1997) Alcohol consumption and mortality among middle-aged and elderly U.S. adults. N Engl J Med 337:1705–1714PubMedCrossRefGoogle Scholar
  47. 47.
    Tirapelli CR, Leone AF, Coelho EB, Resstel LB, Corrêa FM, Lanchote VL, Uyemura SA, Padovan CM, de Oliveira AM (2007) Effect of ethanol consumption on blood pressure and rat mesenteric arterial bed, aorta and carotid responsiveness. J Pharm Pharmacol 59(7):985–993PubMedCrossRefGoogle Scholar
  48. 48.
    Tirapelli CR, Yogi A, Callera GE, Batalhão ME, Carnio EC, Vercesi JA, Queiroz RH, Touyz RM (2009) Acute ethanol administration induces vascular superoxide anion generation without effect on blood pressure in rats: a role for angiotensin II. Hypertension 54:e83Google Scholar
  49. 49.
    Toda N, Ayajiki K (2010) Vascular actions of nitric oxide as affected by exposure to alcohol. Alcohol Alcohol 45(4):347–355PubMedCrossRefGoogle Scholar
  50. 50.
    Touyz RM, Schiffrin EL (2000) Signal transduction mechanisms mediating the physiological and pathophysiological actions of angiotensin II in vascular smooth muscle cells. Pharmacol Rev 52(4):639–672PubMedGoogle Scholar
  51. 51.
    Ushio-Fukai M, Griendling KK, Becker PL, Alexander RW (1999) Role of reactive oxygen species in angiotensin II-induced transactivation of epidermal growth factor receptor in vascular smooth muscle cells. Circulation 100(suppl):I–263Google Scholar
  52. 52.
    Wang Z, Harkins PC, Ulevitch RJ, Han J, Cobb MH, Goldsmith EJ (1997) The structure of mitogen-activated protein kinase p38 at 2.1-AA resolution. Proc Natl Acad Sci U S A 94:2327–2332PubMedCentralPubMedCrossRefGoogle Scholar
  53. 53.
    Wenzel P, Schulz E, Oelze M, Müller J, Schuhmacher S, Alhamdani MS, Debrezion J, Hortmann M, Reifenberg K, Fleming I, Münzel T, Daiber A (2008) AT1-receptor blockade by telmisartan upregulates GTP-cyclohydrolase I and protects eNOS in diabetic rats. Free Radic Biol Med 45(5):619–626PubMedCrossRefGoogle Scholar
  54. 54.
    Xu Y, Bialik S, Jones B, Iimuro Y, Kitsis R, Srinivasan A, Brenner D, Czaja M (1998) NFk-B activation converts a hepatocyte cell line TNF-α response from proliferation to apoptosis. Am J Physiol Cell Physiol 275:C1058–C1066Google Scholar
  55. 55.
    Yang ZW, Wang J, Zheng T, Altura BT, Altura BM (2002) Roles of tyrosine kinase-, 1-phosphatidylinositol 3-kinase-, and mitogen-activated protein kinase-signaling pathways in ethanol-induced contractions of rat aortic smooth muscle: possible relation to alcohol-induced hypertension. Alcohol 28(1):17–28PubMedCrossRefGoogle Scholar
  56. 56.
    Yogi A, Callera GE, Hipólito UV, Silva CR, Touyz RM, Tirapelli CR (2010) Ethanol-induced vasoconstriction is mediated via redox-sensitive cyclo-oxygenase-dependent mechanisms. Clin Sci (Lond) 118(11):657–668CrossRefGoogle Scholar
  57. 57.
    Yogi A, Callera GE, Mecawi AS, Batalhão ME, Carnio EC, Antunes-Rodrigues J, Queiroz RH, Touyz RM, Tirapelli CR (2012) Acute ethanol intake induces superoxide anion generation and mitogen-activated protein kinase phosphorylation in rat aorta: a role for angiotensin type 1 receptor. Toxicol Appl Pharmacol 264(3):470–478PubMedCrossRefGoogle Scholar
  58. 58.
    Yogi A, O’Connor SE, Callera GE, Tostes RC, Touyz RM (2010) Receptor and nonreceptor tyrosine kinases in vascular biology of hypertension. Curr Opin Nephrol Hypertens 19(2):169–176PubMedCrossRefGoogle Scholar
  59. 59.
    Yoshitani T, Yagi H, Inotsume N, Yasuhara M (2002) Effect of experimental renal failure on the pharmacokinetics of losartan in rats. Biol Pharm Bull 25(8):1077–1083PubMedCrossRefGoogle Scholar

Copyright information

© University of Navarra 2014

Authors and Affiliations

  • Natália A. Gonzaga
    • 1
    • 2
  • Glaucia E. Callera
    • 3
  • Alvaro Yogi
    • 3
  • André S. Mecawi
    • 4
  • José Antunes-Rodrigues
    • 4
  • Regina H. Queiroz
    • 5
  • Rhian M. Touyz
    • 3
  • Carlos R. Tirapelli
    • 1
    • 6
  1. 1.Departamento de Enfermagem Psiquiátrica e Ciências Humanas, Laboratório de FarmacologiaEscola de Enfermagem de Ribeirão Preto, USPRibeirão PretoBrazil
  2. 2.Programa de Pós-Graduação em FarmacologiaFaculdade de Medicina de Ribeirão Preto, USPRibeirão PretoBrazil
  3. 3.Kidney Research Centre, Ottawa Health Research InstituteUniversity of OttawaOttawaCanada
  4. 4.Departamento de FisiologiaFaculdade de Medicina de Ribeirão Preto, USPRibeirão PretoBrazil
  5. 5.Departamento de Análises Clínicas, Toxicológicas e BromatológicasFaculdade de Ciências Farmacêuticas de Ribeirão Preto, USPSão PauloBrazil
  6. 6.Laboratório de Farmacologia, Escola de Enfermagem de Ribeirão PretoUniversidade de São PauloRibeirão PretoBrazil

Personalised recommendations