Blocking systemic nitric oxide production alters neuronal activation in brain structures involved in cardiovascular regulation during polymicrobial sepsis

Author(s)

Pascoti Bruhn, Fernando Henrique ^[1] ; Farias Correa, Pollyanna Barbosa ^[1] ; Oliveira-Pelegrin, Gabriela Ravanelli ^[1] ; Alves Rocha, Maria Jose ^[2]

Affiliation

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, BR-14040904 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Odontol Ribeirao Preto, Dept Morfol Estomatol & Fisiol, BR-14040904 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Neuroscience Letters; v. 453, n. 3, p. 141-146, APR 10 2009.
• Web of Science Citations: 8

Abstract

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 24 h after the surgeries and the brains were removed and processed for Fos immunocytochemistry We observed an increase (P < 0.001) in c-fos expression 6 h after CLP in the area postrema (AP), nucleus of he tractus solitarius (NTS), ventral lateral medulla (VLM), locus coeruleus (LC) and parabrachial nucleus (PB). At 24 h 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 6 h after CLR but showed an opposite effect at 24 h, 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 24 h. 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. (C) 2009 Elsevier Ireland Ltd. All rights reserved. (AU)

• FAPESP's process: 07/08532-0 - Neuroendocrine alterations during experimental sepsis induced by cecal ligation and puncture
• Grantee: Maria José Alves da Rocha
• Support Opportunities: Regular Research Grants