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Reactive Oxygen Species via Rac1‐Dependent Pathway in Rostral Ventrolateral Medulla Enhance Central Sympathetic Outflow in Stroke‐Prone Spontaneously Hypertensive Rats
Author(s) -
Sagara Yoji,
Hirooka Yoshitaka,
Nozoe Masatsugu,
Koga Yasuaki,
Sunagawa Kenji
Publication year - 2006
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.20.4.a357-a
Subject(s) - rostral ventrolateral medulla , medicine , stroke (engine) , outflow , medulla , reactive oxygen species , cardiology , endocrinology , medulla oblongata , neuroscience , central nervous system , biology , microbiology and biotechnology , mechanical engineering , physics , meteorology , engineering
Reactive oxygen species (ROS) are increased in the rostral ventrolateral medulla (RVLM) in the brainstem, where the vasomotor center is located, in stroke‐prone spontaneously hypertensive rats (SHRSP). A key source of ROS is the NADPH oxidase, which is regulated by the small GTP‐binding protein Rac1. The aim of the present study was to examine whether Rac1 mediates the ROS production in the RVLM. Rac1 activity in the RVLM examined by pull‐down assay was enhanced in SHRSP compared with WKY. Transfection of adenovirus vectors encoding dominant‐negative Rac1 (AdN17Rac1) into the RVLM decreased blood pressure in both WKY and SHRSP. The magnitude of decreases was, however, greater in SHRSP than in WKY. Twenty‐four hour urinary norepinephrine excretion was decreased after transfection of AdN17Rac1 in SHRSP, but not in WKY. ROS production in the RVLM measured by in vivo microdialysis was greater in SHRSP than in WKY, which was decreased by transfection of AdN17Rac1 in SHRSP. Blood pressure and ROS production were increased during infusion of angiotensin II into the RVLM, and the increases in these variables were greater in SHRSP than in WKY. These effects were attenuated by transfection of AdN17Rac1. These results suggest that the increased ROS production mediated by Rac1 in the RVLM of SHRSP is involved in enhanced central sympathetic outflow. Activation of the brain angiotensin II might be related to this mechanism.