title: Neonatal endotoxin exposure changes neuroendocrine, cardiovascular function and mortality during polymicrobial sepsis in adult rats.
abstract: Our aim was to investigate whether neonatal LPS challenge may improve hormonal, cardiovascular response and mortality, this being a beneficial adaptation when adult rats are submitted to polymicrobial sepsis by cecal ligation and puncture (CLP). Fourteen days after birth, pups received an intraperitoneal injection of lipopolysaccharide (LPS; 100μg/kg) or saline. After 8-12 weeks, they were submitted to CLP, decapitated 4, 6 or 24h after surgery and blood was collected for vasopressin (AVP), corticosterone and nitrate measurement, while AVP contents were measured in neurohypophysis, supra-optic (SON) and paraventricular (PVN) nuclei. Moreover, rats had their mean arterial pressure (MAP) and heart rate (HR) evaluated, and mortality and bacteremia were determined at 24h. Septic animals with neonatal LPS exposure had higher plasma AVP and corticosterone levels, and higher c-Fos expression in SON and PVN at 24h after surgery when compared to saline treated rats. The LPS pretreated group showed increased AVP content in SON and PVN at 6h, while we did not observe any change in neurohypophyseal AVP content. The nitrate levels were significantly reduced in plasma at 6 and 24h after surgery, and in both hypothalamic nuclei only at 6h. Septic animals with neonatal LPS exposure showed increase in MAP during the initial phase of sepsis, but HR was not different from the neonatal saline group. Furthermore, neonatally LPS exposed rats showed a significant decrease in mortality rate as well as in bacteremia. These data suggest that neonatal LPS challenge is able to promote beneficial effects on neuroendocrine and cardiovascular responses to polymicrobial sepsis in adulthood.
authors.affiliation: Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Rafael Simone
authors.initials: RS
authors.lastname: Saia
authors.forename: Gabriela Ravanelli
authors.initials: GR
authors.lastname: Oliveira-Pelegrin
authors.forename: Maria Emília Nadaletto Bonifácio
authors.initials: ME
authors.lastname: da Silva
authors.forename: Fábio Alves
authors.initials: FA
authors.lastname: Aguila
authors.forename: José
authors.initials: J
authors.lastname: Antunes-Rodrigues
authors.forename: Maria José Alves
authors.initials: MJ
authors.lastname: Rocha
authors.forename: Evelin Capellari
authors.initials: EC
authors.lastname: Cárnio
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001127:Arginine Vasopressin / Q000097:blood; D016470:Bacteremia / Q000382:microbiology / Q000503:physiopathology / Q000517:prevention & control; D001794:Blood Pressure; D002319:Cardiovascular System / Q000187:drug effects*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009490:Neurosecretory Systems / Q000187:drug effects*; D009569:Nitric Oxide / Q000097:blood; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D010904:Pituitary Gland, Posterior / Q000378:metabolism; D011247:Pregnancy; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000382:microbiology / Q000503:physiopathology / Q000517:prevention & control*; D013495:Supraoptic Nucleus / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D016760:Proto-Oncogene Proteins c-fos; D001127:Arginine Vasopressin; D009569:Nitric Oxide