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Effects of endogenous H2S production inhibition on the homeostatic responses induced by acute high-salt diet consumption

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Abstract

The gaseous modulator hydrogen sulfide (H2S) is synthesized, among other routes, by the action of cystathionine-γ-lyase (CSE) and importantly participates in body fluid homeostasis. Therefore, the present study aimed to evaluate the participation of H2S in behavioral, renal and neuroendocrine homeostatic responses triggered by the acute consumption of a high Na+ diet. After habituation, adult male Wistar rats were randomly distributed and maintained for seven days on a control [CD (0.27% of Na+)] or hypersodic diet [HD (0.81% of Na+)]. CD and HD-fed animals were treated with DL-Propargylglycine (PAG, 25 mg/kg/day, ip) or vehicle (0.9% NaCl in equivalent volume) for the same period. At the end of the experiment, animals were euthanized for blood and tissue collection. We demonstrated that a short-term increase in dietary Na+ intake, in values that mimic the variations in human consumption (two times the recommended) significantly modified hydroelectrolytic homeostasis, with repercussions in the hypothalamic-neurohypophysial system and hypothalamic–pituitary–adrenal axis function. These findings were accompanied by the development of a clear inflammatory response in renal tubular cells and microvascular components. On the other hand, the inhibition of the endogenous production of H2S by CSE provided by PAG treatment prevented the inflammation induced by HD. In the kidney, PAG treatment induced the overexpression of inducible nitric oxide synthase in animals fed with HD. Taken together, these data suggest, therefore, that HD-induced H2S production plays an important proinflammatory role in the kidney, apparently counter regulating nitric oxide actions in renal tissue.

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Acknowledgements

We would like to thank the technical support of Luis Felipe Cunha dos Reis (Department of Physiological Sciences, UNIFAL/MG) and Milene Mantovani Lopes Mata (Department of Physiology, FMRP/USP).

Funding

Coordenacao de Aperfeicoamento de Pessoal de Nível Superior (CAPES, individual grant for A. M. M.) and Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG, research grant for S. G. R., APQ-02261–14).

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Authors and Affiliations

  1. Department of Physiological Sciences, Biomedical Sciences Institute, Federal University of Alfenas, Minas Gerais, Brazil

    Andreia Mara Moreira, Samuel Amorin Grisote & Silvia Graciela Ruginsk

  2. Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil

    Heloisa Della Colleta Francescato, Terezila Machado Coimbra, Lucila Leico Kagohara Elias & José Antunes-Rodrigues

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  1. Andreia Mara Moreira
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Contributions

AMM and SAG conducted all the animal experiments and data analyses. SGR designed and supervised the experiments. HDCF, TMC, LLKE and JAR provided their expertise and carefully revised the text.

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Correspondence to Silvia Graciela Ruginsk.

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All the procedures were conducted in accordance with the Guide for the Care and Use of Animals of the National Institute of Health and the ethical principles of the Brazilian Society of Sciences in Laboratory Animals (SBCAL; available at < https://www.cobea.org.br >). The present protocols were also approved by the Ethics Committee for Animal Use of the Federal University of Alfenas – UNIFAL/MG (CEUA 613/2015).

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Moreira, A.M., Grisote, S.A., Francescato, H.D.C. et al. Effects of endogenous H2S production inhibition on the homeostatic responses induced by acute high-salt diet consumption. Mol Cell Biochem 476, 715–725 (2021). https://doi.org/10.1007/s11010-020-03938-w

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