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Hypoxia‐inducible factor‐1/heme oxygenase‐1 cascade activates nitric oxide synthase I/protein kinase G signaling pathway at rostral ventrolateral medulla during mevinphos intoxication in the rat
Author(s) -
Chang Alice Y.W.,
Chan Samuel H.H.
Publication year - 2007
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.21.5.a469-d
Subject(s) - rostral ventrolateral medulla , heme oxygenase , microinjection , nitric oxide synthase , chemistry , nitric oxide , medicine , endocrinology , urotensin ii , heme , biology , medulla oblongata , biochemistry , receptor , central nervous system , enzyme
The organophosphate poison mevinphos (Mev) induces its sympathoexcitatory phase (Phase I) of cardiovascular responses via nitric oxide (NO) produced by NO synthase I (NOS I) in the rostral ventrolateral medulla (RVLM), the origin of sympathetic vasomotor tone. This study evaluated the regulatory role of heme oxygenase‐1 (HO‐1) and its key transcription factor, hypoxia‐inducible factor‐1 (HIF‐1), in this process. In Sprague‐Dawley rats anesthetized with propofol, microinjection bilaterally of Mev (10 nmol) into the RVLM elicited significant hypoxia, along with nuclear translocation of HIF‐1, in this medullary site. HO‐1, heat shock protein 70 (HSP70), NOS I or protein kinase G (PKG) expression in the RVLM was also upregulated during Phase I Mev intoxication. Pretreatment by microinjection of anti‐HO‐1 antiserum or antisense ho‐1 oligonucleotide bilaterally into the RVLM significantly blunted the augmented expression of HSP70, NOS I or PKG exhibited during this phase of Mev‐induced increase in sympathetic vasomotor activities. Pretreatment with HO‐2 antiserum or antisense ho‐2 oligonucleotide, however, was ineffective. We conclude that HIF‐1/HO‐1 cascade regulates NOS I/PKG signaling via activation of HSP70 in the RVLM during the sympathoexcitatory phase of Mev intoxication.