Efeitos da inibição endógena da produção de h2s nas respostas homeostáticas induzidas pela dieta hipersódica em ratos

Abstract

Sodium (Na+) is the main osmotically active solute of the extracellular fluid, as well as represents the main ion responsible for maintaining the circulating volume, essential for adequate tissue perfusion. Recently, the participation of gaseous modulators in sodium homeostasis has been proposed. Among these gases is hydrogen sulfide (H2S), formed, among other routes, by the action of the enzyme cystathionine-γ-lyase (CSE). In this context, the present study aimed to evaluate the participation of H2S in the homeostatic responses triggered by the acute consumption of hypersodic diet. After being habituated with the standard ground food (NUVILAB®), 72 adult male Wistar rats were kept for seven days on a control [C (0.27% Na+)] or hypersodic diet [S2 (0.54%)/S3(0.81%)], and treated with a CSE inhibitor (DL-Propargylglycine, PAG, 25 mg/kg/day, ip, Sigma®) or vehicle (saline). At the end of this period, the animals were euthanized by decapitation. We have shown that the ingestion, even if acute, of an increased amount of Na+ in the diet, in values that attempt to mimic the variations in human consumption (2 to 3 times the recommended), significantly modified the Na+ and water balance, with repercussions on at least two neuroendocrine axes (hypothalamus-neurohypophysis and hypothalamus-pituitary-adrenal axis). Interestingly, all these adaptive responses evolved even in the absence of evident behavioral changes (reflex increase in water intake) and plasma (hyperosmolality/hypernatremia). These findings were accompanied by the development of a clear inflammatory response in tubular and microvascular renal elements, and an also present but less intense response in a large systemic artery (aorta). In turn, the inhibition of endogenous H2S production by CSE, through PAG treatment, prevented the inflammation induced by hypersodic diet, in addition to modulating hormone secretion. In summary, our data suggest that H2S has an important proinflammatory role, apparently counterregulating the actions of NO, which may be involved in acute changes triggered by excessive Na+ consumption. These changes, if maintained in the long term, may contribute to the pathogenesis of local, mainly renal, as well as systemic disorders, such as arterial hypertension.