Role of central NO-cGMP pathway in vasopressin and oxytocin gene expression during sepsis.
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 NO-cGMP 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 μg/μL), 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 PVN of the hypothalamus during polymicrobial sepsis.
Oliveira-Pelegrin
Gabriela Ravanelli
GR
Departamento de Morfologia, Estomatologia e Fisiologia, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
Aguila
Fábio Alves
FA
Basso
Paulo José
PJ
Rocha
Maria José Alves
MJ
D000818:Animals; D001127:Arginine Vasopressin / Q000235:genetics / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D010069:Oxadiazoles / Q000494:pharmacology; D010121:Oxytocin / Q000235:genetics / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology*; D013495:Supraoptic Nucleus / Q000187:drug effects / Q000378:metabolism
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D011810:Quinoxalines; D001127:Arginine Vasopressin; D009569:Nitric Oxide; D010121:Oxytocin; D006152:Cyclic GMP