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| Author(s): |
Letícia Antunes Athayde
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | Ribeirão Preto. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) |
| Defense date: | 2007-08-03 |
| Examining board members: |
Maria Jose Alves da Rocha;
Evelin Capellari Carnio;
Lucia Helena Faccioli
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| Advisor: | Maria Jose Alves da Rocha |
| Abstract | |
During sepsis occurs an increase in the production of inflammatory mediators, including leukotrienes (LTs), which is accompanied by hypotension and a consequent increase in vasopressin (AVP) secretion. This picture characterizes the initial phase of sepsis and contrasts with the late phase, when AVP secretion declines, despite the progressive hypotension. Recent studies revealed that vasopressinergic neurons have a high content of LTC4 synthase, a critical enzyme in LT synthesis, and that neural structures with input to these neurons contain receptors for LTs, suggesting that they may play a role in regulating AVP secretion. This study evaluated the role of central and peripheral LTs in the time course of AVP secretion during experimentally induced. Male wistar rats received an i.c.v. or i.p. injection of MK-886 (1.0g/kg or 1.0mg/kg), a LTs biosynthesis inhibitor, or vehicle 1h before cecal ligation and puncture (CLP) or sham operation. In one group of animals, the survival rate was monitored for 5 days. Another group, the animals was decapitated at 0, 4, 6, 18 and 24h after CLP or sham operation, and blood was collected for hematocrit, serum sodium, plasma osmolality, plasma protein, serum nitrate and plasma AVP levels measurement. The neurohypophysis was removed for AVP content measurement, and the hypothalamus dissected for quantification (Western blot) of the LTC4 synthase at 0, 4 and 6h. The CLP increased plasma AVP levels in the initial phase of sepsis, which was blocked by the central and reduced by the peripheral administration of MK-886. The decrease in the neurohypophyseal AVP content was partially reversed by the both via of administration. The time-course increase of serum NO, hematocrit and hypothalamus LTC4 synthase was reduced, not modified and blocked respectively by the central administration of MK-886. By other way, the peripheral administration of the LTs blocker did not alter the serum NO and hypothalamus LTC4 synthase, but abolished the increase of hematocrit. The CLP also reduced temporally the plasma protein and the central administration of MK-886 did not modify whereas the peripheral administration reversed this effect. The high mortality observed after CLP was reduced by central but did not modify by peripheral administration of MK-886. In the final phase of sepsis the plasma AVP remained in the basal levels and the administration of LTs blocker by both via did not alter these hormone levels. The results suggest that the central and peripheral LTs are involved in the AVP secretion regulation during experimental sepsis. (AU) | |