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Master's Dissertation
DOI
10.11606/D.60.2007.tde-01042009-141522
Document
Author
Full name
Letícia Antunes Athayde
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2007
Supervisor
Committee
Rocha, Maria Jose Alves da (President)
Carnio, Evelin Capellari
Faccioli, Lucia Helena
Title in Portuguese
Participação dos leucotrienos na secreção de vasopressina durante sepse experimental
Keywords in Portuguese
CLP
leucotrienos
NO
Sepse polimicrobiana
vasopressina
Abstract in Portuguese
Durante a sepse ocorre aumento da produção de mediadores inflamatórios, dentro os quais leucotrienos (LTs), além de hipotensão seguida de aumento da secreção de vasopressina (AVP) na fase inicial e diminuição na fase tardia, a despeito da progressão da hipotensão. Estudos recentes revelam que neurônios vasopressinérgicos contêm alto conteúdo da enzima LTC4 sintase, e também há relatos de que estruturas neurais que se conectam a esses neurônios possuem receptores para LTs, sugerindo que os mesmos podem ter uma tarefa na secreção de AVP. Este estudo avaliou a participação dos LTs centrais e periféricos sobre a secreção temporal de AVP durante a sepse experimental. Ratos Wistar receberam injeção i.c.v. de MK-886 (1.0g/kg) e i.p. (1.0mg/kg), um inibidor da síntese de leucotrienos, ou DMSO 5% (veículo) e foram submetidos ao estímulo séptico por ligadura e perfuração cecal (CLP) ou à operação fictícia. Em um grupo de animais, a sobrevida foi avaliada durante 5 dias. Em outro grupo, os animais foram decapitados 0, 4, 6, 18 e 24h após a cirurgia e o sangue processado para determinação do hematócrito, sódio sérico, osmolalidade, proteínas, nitrato sérico e AVP plasmática. A neurohipófise foi coletada para a determinação do conteúdo de AVP, e o hipotálamo dissecado para a quantificação (Western blot) da LTC4 sintase nos tempos 0, 4 e 6h. A CLP aumentou a concentração de AVP plasmática na fase inicial da sepse, que foi bloqueada pela administração central e reduzida pela periférica de MK-886. A diminuição do conteúdo neurohipofisário de AVP foi revertido parcialmente pelas duas vias de administração. Os aumentos temporais de NO sérico, de hematócrito e de LTC4 sintase hipotalâmica foram reduzidos, não alterados e bloqueados, respectivamente, pela administração central de MK-886. Por outro lado, a administração periférica não alterou o NO sérico e LTC4 sintase, mas aboliu o aumento do hematócrito. A CLP também reduziu temporalmente as proteínas plasmáticas e a administração central de MK-886 não alterou, enquanto a periférica reverteu esta redução. A alta mortalidade observada após CLP foi reduzida pela administração central e não modificada pela periférica. Na fase tardia da sepse, a AVP plasmática se manteve em concentrações basais e o bloqueador de LTs administrado pelas duas vias não alterou essas concentrações. Os resultados sugerem que os LTs centrais e periféricos estão envolvidos na regulação da secreção de AVP durante sepse experimental.
Title in English
Participation of leukotrienes in vasopressin secretion during experimental sepsis
Keywords in English
CLP
leukotrienes
NO
Polymicrobial sepsis
vasopressin
Abstract in English
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.
 
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Publishing Date
2010-09-17
 
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