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Cyclooxygenase‐2‐dependent neuroinflammation and oxidative stress in rostral ventrolateral medulla contribute to neurogenic hypertension following chronic systemic inflammation
Author(s) -
Wu Kay Li-Hui,
Chan Julie Yu-Hwa,
Chan Samuel H.H.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.872.38
Subject(s) - rostral ventrolateral medulla , neuroinflammation , oxidative stress , apocynin , inflammation , microglia , proinflammatory cytokine , systemic inflammation , endocrinology , nitric oxide , cyclooxygenase , angiotensin ii , medicine , nitric oxide synthase , chemistry , nadph oxidase , medulla oblongata , central nervous system , blood pressure , biochemistry , enzyme
Inflammation plays a significant role in pathogenesis of hypertension. This study aimed to investigate whether chronic systemic inflammation (CSI) induces hypertension via triggering neuroinflammation and oxidative stress in the rostral ventrolateral medulla (RVLM) where the sympathetic premotor neurons are located. CSI was induced via a continuous intraperitoneal infusion of E coli. Lipopolysaccharide (LPS) to normotensive Sprague‐Dawley rats. CSI was confirmed by a sustained increase in plasma level of C‐reactive protein. CSI resulted in the activation of perivascular microglia, increases in proinflammatory cytokine and intercellular adhesion molecule‐1 expression, and decrease of endothelial nitric oxide synthase expression in RVLM. CSI also promoted a long‐term pressor response accompanied by an increase in tissue level of superoxide and a reduction in expression of a voltage‐gated K + channel, Kv4.3, in the RVLM. CSI‐induced hypertension and cellular events were significantly prevented by intracisternal (IC) infusion of cytokine or cyclooxygenase‐2 (COX‐2) inhibitors. CSI‐induced hypertension was also attenuated by IC infusion of tempol. These data suggest that CSI activates the perivascular microglia to evoke the COX‐2‐dependent neuroinflammation and oxidative stress in the RVLM, leading to oxidative stress‐associated neurogenic hypertension.