Blocking peripheral leukotrienes decreases plasma vasopressin concentration during the early phase of experimental sepsis

Abstract

IntroductionEvidence suggests that leukotrienes and nitric oxide may have a role in vasopressin secretion that occurs during the early phase of sepsis. Moreover, leukotrienes are thought to affect nitric oxide production. Our objective was to analyze the effect of blocking leukotrienes on plasma nitric oxide and vasopressin levels. Materials and Methods: Male Wistar rats received i.p. injections of MK‐886 (1.0, 2.0 or 4.0 mg/kg) or vehicle (DMSO 5%) 1h before cecal ligation and puncture (CLP) or sham operation. In one group the survival rate was monitored for 3 days. In another group, the animals were decapitated at 0, 4, and 24h after CLP or sham operation, and blood was collected for hematocrit, sodium, vasopressin and nitrate measurement.ResultsWe observed an increase in NO production at 24 h and in hematocrit and vasopressin at 4h after CLP; serum sodium levels remained unchanged. The survival rate after 3 days was 20% in the CLP group. Pretreatment with any dose of MK‐886 did not diminish NO production or affect serum sodium levels, nor did it alter the survival rate. However, vasopressin secretion was affected in a dose‐dependent manner, while hematocrit decreased only with 1mg of the drug.ConclusionThe results suggest that peripheral leukotrienes affect the secretion of vasopressin in the early phase of sepsis and that this alteration seems to be independent of nitric oxide production.