Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Secondary infections after burn are common and are a major contributor to morbidity and mortality. We previously showed that burn disrupted proximal gut mucosal homeostasis through increased epithelial cell apoptosis. In the present study, we sought to determine whether proximal gut mucosal disruption is additively affected by secondary endotoxemia after a severe burn. ⋯ Results showed that proximal gut mucosa impairment occurred 12 h after injury, including significantly decreased proximal gut wet weight, gut mucosal height, and epithelial cell number associated with increased proximal gut epithelial apoptosis (P < 0.05). This impairment diminished 72 h after burn. Second-hit endotoxemia caused additional proximal gut mucosa damage with decreased proximal gut weight, cell number, and mucosal height (P < 0.05) and significantly increased small intestinal epithelial apoptosis and mucosal atrophy, even after the first event, indicating a second detrimental effect of endotoxemia after the initial injury.
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We have recently shown that A3 adenosine receptors and P2Y2 purinergic receptors play an important role in neutrophil chemotaxis. Chemotaxis of neutrophils to sites of infections is critical for immune defense. However, excessive accumulation of neutrophils in the lungs can cause acute lung tissue damage. ⋯ Survival after 24 h was significantly lower in WT mice (37.5%) than in A3KO or P2Y2KO mice (82.5%; P < 0.05). These data suggest that A3 and P2Y2 receptors are involved in the influx of neutrophils into the lungs after sepsis. Thus, pharmaceutical approaches that target these receptors might be useful to control acute lung tissue injury in sepsis.
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Sepsis is associated with an activation of the renin-angiotensin system and causes acute kidney injury. The aim was to examine the effects of a low, nondepressor dose of the selective angiotensin II type 1 receptor antagonist candesartan on renal hemodynamics and function in endotoxemic rats. Endotoxemia was induced in Sprague-Dawley rats by a dose of LPS (Escherichia coli O127:B8; 7.5 mg kg(-1), i.p.). ⋯ LPS-saline). In conclusion, candesartan, in a dose that did not significantly decrease MAP, caused renal vasodilation and markedly improved RBF and intrarenal P(O2) in endotoxemic rats. These findings suggest renoprotective effects of candesartan in sepsis.