Atorvastatin reduces oxidative stress in the rostral ventrolateral medulla of stroke-prone spontaneously hypertensive rats.
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.
Kishi
Takuya
T
Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Hirooka
Yoshitaka
Y
Shimokawa
Hiroaki
H
Takeshita
Akira
A
Sunagawa
Kenji
K
D000818:Animals; D000069059:Atorvastatin; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D009638:Norepinephrine / Q000652:urine; D018384:Oxidative Stress / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D013564:Sympathetic Nervous System / Q000187:drug effects; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D017392:Thiobarbituric Acid Reactive Substances; D009569:Nitric Oxide; D000069059:Atorvastatin; D009638:Norepinephrine