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Atorvastatin reduces sympathetic nerve activity through the inhibition of Rac1/NAD (P) H oxidase and upregulation of Mn‐SOD in SHRSP
Author(s) -
Kishi Takuya,
Hirooka Yoshitaka,
Ito Koji,
Araki Shuichiro,
Konno Satomi,
Sunagawa Kenji
Publication year - 2009
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.23.1_supplement.1008.6
Subject(s) - rostral ventrolateral medulla , oxidative stress , endocrinology , medicine , chemistry , superoxide dismutase , nadph oxidase , cytosol , nad+ kinase , nox1 , p22phox , oxidase test , atorvastatin , pharmacology , blood pressure , heart rate , biochemistry , enzyme
Background Statin is consider to protect for neuroplasticity. We demonstrated that oral administration of atorvastatin decreases sympathetic nerve activity (SNA) through the anti‐oxidant effect in rortral ventrolateral medulla (RVLM) of stroke‐prone spontaneously hypertensive rats (SHRSP). We hypothesized that atorvastatin might protect for neuroplasticity by reduction of oxidative stress in RVLM of SHRSP. Methods and Results In SHRSP, intracerebroventricular infusion of atorvastatin (20 μg/kg/day) (ATORVA) for 14 days significantly reduced systolic blood pressure, heart rate and SNA (‐28±3 %, n=5, P<0.01) in comparison with vehicle infusion (CNT). In the RVLM, ATORVA decreased oxidative stress, Rac1 and NAD (P) H oxidase activity. ATORVA also significantly lowered the expression of Rac1, gp91phox, p22phox in membrane fraction, and p47phox in cytosolic fraction. In contrast, the expression level of Rac1 in cytosolic fraction and Mn‐superoxide dismutase (Mn‐SOD) activity were significantly increased in ATORVA. Conclusion In the RVLM of SHRSP, atorvastatin inhibits membrane translocation of Rac1 and NAD (P) H oxidase subunits and upregulates Mn‐SOD activity, which contribute to the inhibition of oxidative stress in the RVLM, protection for neural plasticity and the sympatho‐inhibitory effect.