Blocking peripheral leukotrienes does not decrease the peripheral nitric oxide production and does not affect hydroelectrolity b

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Thalita Freitas Martins  thalita@fcfrp.usp.br (1)Gabriela R. O. Pelegrin (1), Camila Henrique Coelho (1), Lucia Helena Faccioli (2), Maria José Alves da Rocha (1)

(1) Departamento de Morfologia, Estomatologia e Fisiologia, FORP-USP, Ribeirão Preto, SP, Brazil, (2) Departamento de ....... FCFRP-USP, Ribeirão Preto, SP, Brazil

Introduction: Recently in our laboratory it was seen that the central or peripheral administration of MK-886 (a LTs biosynthesis inhibitor) abolished or reduced the secretion of AVP in the initial phase of the sepsis. Furthermore, was observed that in this phase occurs an increase of the enzyme LTC₄ that is found usually in the hypothalamic neurons that synthetize vasopressin. Additionally we saw that the central administration of MK-886, but no the peripheral, reduced the increase of the enzyme LTC₄ and of serum nitrate that usually occurs during the sepsis. Those data suggest that the leukotrienes have a role in the vasopressin secretion that could occur direct or indirectly through the production of nitric oxide. Since vasopressin secretion is also stimulated by hydroelectrolitic balance our Objective was to analyze the effect of blocking peripheral leukotrienes in the osmolality and hematocrit during experimental sepsis. Materials and Methods:  Male Wistar rats received i.p. injection of MK-886 (2.0 or 4.0 mg/kg) or vehicle (DMSO 5%) 1h before cecal ligation and puncture (CLP) or sham operation. In one group of animals, the survival rate was monitored for 3 days. Another group, the animals was decapitated at 0, 4, and 24h after CLP or sham operation, and blood was collected for hematocrit, plasma osmolality and serum nitrate levels measurement. Results: The serum NO production increased 24 h after CLP and the peripheral administration of the LTs blocker did not decrease this production (p<0,001). The hematocrit increased 4h after CLP and the pretreatment with MK-886 did not modify this effect (p<0,001). The plasma osmolality showed temporal alterations during the analyzed times and the MK-886 also did not modify these parameters (p<0,05). The mortality rate also was not affected by the drug (p<0,15). Conclusion: The results suggest that the peripheral LTs does not affect  the hydroelectrolitic parameters neither the survival rate during experimental sepsis.