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Role of central NO-cGMP pathway in vasopressin and oxytocin gene expression during sepsis
Gabriela Ravanelli Oliveira-Pelegrin, Fábio Alves Aguila, Paulo José Basso, Maria José Alves Rocha ∗
Departamento de Morfologia, Estomatologia e Fisiologia, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil
article
info
Article history:
Received 29 March 2010
Received in revised form 26 June 2010
Accepted 28 June 2010
Available online 16 July 2010
Keywords:
Hypothalamus
Polymicrobial sepsis
Real-time PCR
ODQ
Nitric oxide
Soluble guanylate cyclase
abstract
Sepsis induces massive production of inflammatory mediators, such as nitric oxide (NO), and causes neuroendocrine and cardiovascular alterations. This study investigates the involvement of the central NOcGMP pathway in arginine vasopressin (AVP) and oxytocin (OXY) gene expression during sepsis induced by cecal ligation and puncture (CLP). Male Wistar rats received an i.c.v. injection of ODQ (0.25 g/ L), a selective inhibitor of the heme site of soluble guanylate cyclase, or of 1% dymethilsulfoxide (DMSO), as vehicle. Thirty minutes after the injections, sepsis was induced by cecal ligation and puncture or the animals were sham operated. The ODQ pre-treatment did not alter the progressive NO increase observed after CLP. In the supraoptic nucleus (SON), this pretreatment increased the relative gene expression ratio of AVP and OXY in the initial phase of sepsis, but in the late phase, the gene expression of both hormones was reduced. In the paraventricular nucleus (PVN), soluble guanylate cyclase inhibition caused an even larger decrease in the relative gene expression ratio of AVP and OXY during sepsis. These results are indicative of a role of the NO-cGMP pathway in hormonal synthesis in the SON and