Document Detail

Pioglitazone exerts protective effects against stroke in stroke-prone spontaneously hypertensive rats, independently of blood pressure.
MedLine Citation:
PMID:  17885259     Owner:  NLM     Status:  MEDLINE    
BACKGROUND AND PURPOSE: Very recent subgroup analysis from the PROspective pioglitAzone Clinical Trial In macroVascular Events has shown that pioglitazone reduces the risk of recurrent stroke in type 2 diabetic patients. However, the underlying mechanism of stroke prevention by pioglitazone is unknown. Our aim was to examine the effect of pioglitazone on hypertension-based stroke in rats. METHODS: Pioglitazone (1 mg x kg(-1) x d(-1)) was orally administered to stroke-prone spontaneously hypertensive rats (SHRSP) to examine the effect on incidental stroke, cerebrovascular injury, brain inflammation, oxidative stress, and vascular endothelial dysfunction induced by hypertension. RESULTS: Treatment of SHRSP with pioglitazone for 4 weeks, without affecting blood pressure and blood glucose values, improved vascular endothelial dysfunction (P<0.05), suppressed remodeling of the middle cerebral artery (P<0.05) and brain microvessels (P<0.05), and inhibited brain macrophage infiltration (P<0.05) and the upregulation of brain monocyte chemoattractant protein-1 and tumor necrosis factor-alpha expression (P<0.01). Furthermore, pioglitazone treatment significantly delayed the onset of stroke signs and death in SHRSP (P<0.05). These beneficial effects of pioglitazone on cerebrovascular injury and stroke in SHRSP were associated with a reduction of brain and vascular superoxide via the inhibition of NADPH oxidase activity. CONCLUSIONS: Our work provides the first evidence that pioglitazone significantly protects against hypertension-induced cerebrovascular injury and stroke by improving vascular endothelial dysfunction, inhibiting brain inflammation, and reducing oxidative stress. These beneficial effects of pioglitazone were independent of blood pressure or blood sugar values. Thus, pioglitazone appears to be a potential therapeutic agent for stroke in type 2 diabetes with hypertension.
Taishi Nakamura; Eiichiro Yamamoto; Keiichiro Kataoka; Takuro Yamashita; Yoshiko Tokutomi; Yi-Fei Dong; Shinji Matsuba; Hisao Ogawa; Shokei Kim-Mitsuyama
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-09-20
Journal Detail:
Title:  Stroke; a journal of cerebral circulation     Volume:  38     ISSN:  1524-4628     ISO Abbreviation:  Stroke     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-10-30     Completed Date:  2007-11-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0235266     Medline TA:  Stroke     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3016-22     Citation Subset:  IM    
Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjyo, Kumamoto 860-8556, Japan.
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MeSH Terms
Blood Glucose / drug effects,  physiology
Blood Pressure / drug effects,  physiology
Cerebral Arteries / drug effects,  metabolism,  physiopathology
Cytokines / drug effects,  metabolism
Diabetes Complications / physiopathology
Disease Models, Animal
Endothelial Cells / drug effects,  metabolism
Hypertension / complications*,  physiopathology
Hypoglycemic Agents / pharmacology,  therapeutic use
Macrophages / drug effects,  metabolism
Microcirculation / drug effects,  metabolism,  physiopathology
NADH, NADPH Oxidoreductases / antagonists & inhibitors,  metabolism
Neuroprotective Agents / pharmacology*,  therapeutic use
Oxidative Stress / drug effects,  physiology
Rats, Inbred SHR
Rats, Inbred WKY
Stroke / drug therapy*,  etiology,  physiopathology*
Superoxides / antagonists & inhibitors,  metabolism
Thiazolidinediones / pharmacology*,  therapeutic use
Treatment Outcome
Reg. No./Substance:
0/Blood Glucose; 0/Cytokines; 0/Hypoglycemic Agents; 0/Neuroprotective Agents; 0/Thiazolidinediones; 11062-77-4/Superoxides; 111025-46-8/pioglitazone; EC 1.6.-/NADH, NADPH Oxidoreductases; EC 1.6.99.-/NADPH oxidase 1

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