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Volume 12 Supplement 5

Sepsis 2008

Blocking central leukotrienes synthesis affects vasopressin release during sepsis


Recent studies revealed that vasopressinergic neurons have a high content of LTC4 synthase, a critical enzyme in cys-leukotriene synthesis that may play a role in regulating vasopressin secretion. The present study investigates the role of this enzyme in arginine vasopressin (AVP) release during experimentally induced sepsis.


Male Wistar rats received an intracerebroventricular injection of MK 886 (1.0 μg/kg), a leukotriene (LT) synthesis inhibitor, or vehicle, 1 hour before cecal ligation and puncture (CLP) or sham operation. In one group of animals the survival rate was monitored for 5 days. In another group, the animals were decapitated 0, 4, 6, 18 and 24 hours after CLP or sham operation, and blood was collected for hematocrit, serum sodium and nitrate, plasma osmolality, protein and arginine AVP determination. The neurohypophysis was removed for quantification of AVP content, and the hypothalamus was dissected for LTC4 synthase analysis by western blot.


The mortality rate after CLP was reduced by the central administration of MK 886. The increase in plasma AVP levels and hypothalamus LTC4 synthase content in the initial phase of sepsis was blocked, whereas the decrease in neurohypophyseal AVP content was partially reversed. The increase of serum nitric oxide and hematocrit was reduced, and the decrease in plasma protein and osmolality was not affected by the LT blocker. In the final phase of sepsis, the plasma AVP level and the hypothalamic LTC4 synthase content were at basal levels. The central administration of MK 886 increased the hypothalamic LTC4 synthase content but did not alter the neurohypophysis AVP content and plasma AVP levels observed during this phase.


These results suggest that the central LTs are involved in the vasopressin release observed during sepsis.


Financial support from FAPESP. Technical support from Nadir Martins Fernandes.

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Athayde, L.A., Oliveira-Pelegrin, G.R., Nomizo, A. et al. Blocking central leukotrienes synthesis affects vasopressin release during sepsis. Crit Care 12, P34 (2008).

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  • Nitric Oxide
  • Arginine
  • Vasopressin
  • Serum Sodium
  • Sham Operation