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

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.

Keywords: High-salt diet; Homeostasis; Hydrogen sulfide; Kidney inflammation.