Inhibition of central leukotrienes and nitric oxide production affects vasopressin secretion induced by polymicrobial sepsis

Background

Sepsis induces an increase in vasopressin (AVP) secretion and massive production of inflammatory mediators, including leukotrienes (LTs) and nitric oxide (NO), which are also produced in the brain and may affect the neuroendocrine system. Our aim was to study the role of central LTs and NO in AVP secretion during polymicrobial sepsis induced by cecal ligation and puncture (CLP).

Methods

Male Wistar rats (250–280 g) received an intracerebroventricular injection of MK-886 (1 μg/kg), an LT biosynthesis inhibitor, or L-NAME (250 μg), an NO synthase inhibitor. Controls received a carrier injection before CLP, or were only sham operated. In one group of animals, survival was monitored for 5 days. In another group, the animals were decapitated at 4, 6 or 24 hours after surgery and blood was collected for measurements of hematocrit, plasma nitrate (NOx) and AVP levels.

Results

CLP caused an increase in plasma AVP levels in the initial phase of sepsis, which was blocked by the central administration of MK-886 and was elevated by intracerebroventricular-injected L-NAME (P < 0.05). This contrasted with the final phase of sepsis, when plasma AVP remained at basal levels and was not altered by the administration of LT and NO blockers. The gradual increase in NOx levels was reduced by MK-886 and blocked by L-NAME. The increase in hematocrit caused by CLP was diminished (P < 0.05) by L-NAME injection, but was not modified by central administration of MK-886. The low survival rates observed after CLP were improved by the central administration of both drugs (P < 0.05).

Conclusion

These results suggest that central LTs and NO differentially affect AVP secretion during CLP-induced experimental sepsis.