TY - JOUR
T1 - Atorvastatin reduces oxidative stress in the rostral ventrolateral medulla of stroke-prone spontaneously hypertensive rats
AU - Kishi, Takuya
AU - Hirooka, Yoshitaka
AU - Shimokawa, Hiroaki
AU - Takeshita, Akira
AU - Sunagawa, Kenji
N1 - Funding Information:
This work was supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (C15590757, C17590745) and, in part, by the Health and Labor Sciences Research Grant for Comprehensive Research in Aging and Health Labor and Welfare of Japan.
PY - 2008/1
Y1 - 2008/1
N2 - Previously, we demonstrated that atorvastatin has sympatho-inhibitory effects with the upregulation of nitric oxide synthase in the brain in stroke-prone spontaneously hypertensive rats (SHRSP), and that reactive oxygen species in the rostral ventrolateral medulla (RVLM), where the vasomotor center is located, mediate the sympatho-excitatory effect. The aim of the present study was to determine if atorvastatin reduces oxidative stress in the RVLM of SHRSP along with the sympatho-inhibitory effect. SHRSP and Wistar-Kyoto (WKY) rats received standard feed with atorvastatin (50mg/kg per day) or standard feed for 30 days. Systolic blood pressure and heart rate were evaluated using the tail-cuff method. Urinary norepinephrine excretion was measured for 24 hours. After 30 days in SHRSP, blood pressure and urinary norepinephrine excretion were significantly lower in the atorvastatin group than in the control group. Thiobarbituric acid-reactive substance (TBARS) levels in the RVLM tissue obtained using the micropunch technique were used as measures of oxidative stress. Prior to the treatment, TBARS levels in the RVLM of SHRSP were significantly higher than those of WKY. After 30 days, TBARS levels in the RVLM of SHRSP were significantly lower in the atorvastatin group than in the control group. After 30 days in WKY, however, there were no differences in blood pressure, urinary norepinephrine excretion, and TBARS levels between the atorvastatin and control groups. These results suggest that atorvastatin reduces oxidative stress in the RVLM of SHRSP, which might contribute to the sympatho-inhibitory effects of atorvastatin in SHRSP.
AB - Previously, we demonstrated that atorvastatin has sympatho-inhibitory effects with the upregulation of nitric oxide synthase in the brain in stroke-prone spontaneously hypertensive rats (SHRSP), and that reactive oxygen species in the rostral ventrolateral medulla (RVLM), where the vasomotor center is located, mediate the sympatho-excitatory effect. The aim of the present study was to determine if atorvastatin reduces oxidative stress in the RVLM of SHRSP along with the sympatho-inhibitory effect. SHRSP and Wistar-Kyoto (WKY) rats received standard feed with atorvastatin (50mg/kg per day) or standard feed for 30 days. Systolic blood pressure and heart rate were evaluated using the tail-cuff method. Urinary norepinephrine excretion was measured for 24 hours. After 30 days in SHRSP, blood pressure and urinary norepinephrine excretion were significantly lower in the atorvastatin group than in the control group. Thiobarbituric acid-reactive substance (TBARS) levels in the RVLM tissue obtained using the micropunch technique were used as measures of oxidative stress. Prior to the treatment, TBARS levels in the RVLM of SHRSP were significantly higher than those of WKY. After 30 days, TBARS levels in the RVLM of SHRSP were significantly lower in the atorvastatin group than in the control group. After 30 days in WKY, however, there were no differences in blood pressure, urinary norepinephrine excretion, and TBARS levels between the atorvastatin and control groups. These results suggest that atorvastatin reduces oxidative stress in the RVLM of SHRSP, which might contribute to the sympatho-inhibitory effects of atorvastatin in SHRSP.
KW - Brain
KW - Hypertension
KW - Oxidative stress
KW - Statin
KW - Sympathetic nervous system
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U2 - 10.1080/10641960701813429
DO - 10.1080/10641960701813429
M3 - Article
C2 - 18214729
AN - SCOPUS:38549092439
VL - 30
SP - 3
EP - 11
JO - Clinical and Experimental Hypertension
JF - Clinical and Experimental Hypertension
SN - 1064-1963
IS - 1
ER -