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Chronic methionine load-induced hyperhomocysteinemia impairs the relaxation induced by bradykinin in the isolated rat carotid

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Abstract

This study investigates the effects of chronic methionine intake on bradykinin (BK)-relaxation. Vascular reactivity experiments were performed on carotid rings from male Wistar rats. Treatment with methionine (0.1, 1 or 2 g kg−1 per day) for 8 and 16 weeks, but not for 2 and 4 weeks, reduced the relaxation induced by BK. Indomethacin, a non-selective cyclooxygenase (COX) inhibitor, and SQ29548, a selective thromboxane A2 (TXA2)/prostaglandin H2 (PGH2) receptor antagonist prevented the reduction in BK-relaxation observed in the carotid from methionine-treated rats. Conversely, AH6809, a selective prostaglandin F2α (PGF2α) receptor antagonist did not alter BK-relaxation in the carotid from methionine-treated rats. The nitric oxide synthase (NOS) inhibitors L-NAME, L-NNA and 7-nitroindazole reduced the relaxation induced by BK in carotids from control and methionine-treated rats. In summary, we found that chronic methionine intake impairs the endothelium-dependent relaxation induced by BK and this effect is due to an increased production of endothelial vasoconstrictor prostanoids (possibly TXA2) that counteracts the relaxant action displayed by the peptide.

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Acknowledgments

We are most grateful to Mirian C. C. de Melo, Juliana A. Vercesi and Mayara S. Gomes for their technical assistance. We thank FAPESP for financial support.

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Authors and Affiliations

  1. Laboratory of Pharmacology, Department of Physics and Chemistry, Faculty of Pharmaceutical Sciences, University of São Paulo (USP), Avenida do Café s/n, Ribeirão Preto, SP, CEP 14040-903, Brazil

    Daniella Bonaventura & Ana Maria de Oliveira

  2. Laboratory of Pharmacology, Department of Psychiatry Nursing and Human Sciences, College of Nursing of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil

    Carlos R. Tirapelli

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  1. Daniella Bonaventura
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  2. Carlos R. Tirapelli
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  3. Ana Maria de Oliveira
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Correspondence to Ana Maria de Oliveira.

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Bonaventura, D., Tirapelli, C.R. & de Oliveira, A.M. Chronic methionine load-induced hyperhomocysteinemia impairs the relaxation induced by bradykinin in the isolated rat carotid. Amino Acids 37, 617–627 (2009). https://doi.org/10.1007/s00726-008-0181-z

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