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

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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.

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Acknowledgements

We thank Juliana T. Rocha, Sonia A. Dreossi, and Juliana Vercesi for technical support. This study was supported by grants from the Canadian Institutes of Health Research, Conselho Nacional de Desenvolvimento Científico e Tecnológico (470556/2010-2), and Fundação de Amparo à Pesquisa do Estado de São Paulo (2010/05815-4).

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Authors and Affiliations

  1. Departamento de Enfermagem Psiquiátrica e Ciências Humanas, Laboratório de Farmacologia, Escola de Enfermagem de Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil

    Natália A. Gonzaga & Carlos R. Tirapelli

  2. Programa de Pós-Graduação em Farmacologia, Faculdade de Medicina de Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil

    Natália A. Gonzaga

  3. Kidney Research Centre, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON, Canada

    Glaucia E. Callera, Alvaro Yogi & Rhian M. Touyz

  4. Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil

    André S. Mecawi & José Antunes-Rodrigues

  5. Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, USP, São Paulo, Brazil

    Regina H. Queiroz

  6. Laboratório de Farmacologia, Escola de Enfermagem de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes 3900, 14040-902, Ribeirão Preto, SP, Brazil

    Carlos R. Tirapelli

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  1. Natália A. Gonzaga
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  2. Glaucia E. Callera
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Correspondence to Carlos R. Tirapelli.

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Gonzaga, N.A., Callera, G.E., Yogi, A. et al. Acute ethanol intake induces mitogen-activated protein kinase activation, platelet-derived growth factor receptor phosphorylation, and oxidative stress in resistance arteries. J Physiol Biochem 70, 509–523 (2014). https://doi.org/10.1007/s13105-014-0331-6

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