Blocking systemic nitric oxide production alters neuronal activation in brain structures involved in cardiovascular regulation during polymicrobial sepsis.
In a previous study, we concluded that overproduction of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) in the late phase of sepsis prevents hypothalamic activation, blunts vasopressin secretion and contributes to hypotension, irreversible shock and death. The aim of this follow-up study was to evaluate if the same neuronal activation pattern happens in brain structures related to cardiovascular functions. Male Wistar rats received intraperitoneal injections of aminoguanidine, an iNOS inhibitor, or saline 30 min before cecal ligation and puncture (CLP) or sham surgeries. The animals were perfused 6 or 24h after the surgeries and the brains were removed and processed for Fos immunocytochemistry. We observed an increase (P<0.001) in c-fos expression 6h after CLP in the area postrema (AP), nucleus of the tractus solitarius (NTS), ventral lateral medulla (VLM), locus coeruleus (LC) and parabrachial nucleus (PB). At 24h after CLP, however, c-fos expression was strongly decreased in all these nuclei (P<0.05), except for the VLM. Aminoguanidine reduced c-fos expression in the AP and NTS at 6h after CLP, but showed an opposite effect at 24h, with an increase in the AP, NTS, and also in the VLM. No such effect was observed in the LC and PB at 6 or 24h. In all control animals, c-fos expression was minimal or absent. We conclude that in the early phase of sepsis iNOS-derived NO may be partially responsible for the activation of brain structures related to cardiovascular regulation. During the late phase, however, this activation is reduced or abolished.
Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
Fernando Henrique Pascoti
FH
Bruhn
Pollyanna Barbosa Farias
PB
Corrêa
Gabriela Ravanelli
GR
Oliveira-Pelegrin
Maria José Alves
MJ
Rocha
D000818:Animals; D031608:Area Postrema / Q000378:metabolism; D002320:Cardiovascular Physiological Phenomena; D006146:Guanidines / Q000494:pharmacology; D008125:Locus Coeruleus / Q000378:metabolism; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000378:metabolism* / Q000382:microbiology; D017552:Solitary Nucleus / Q000378:metabolism
D006146:Guanidines; D016760:Proto-Oncogene Proteins c-fos; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C004479:pimagedine