Document Detail

Beneficial effects of pioglitazone on left ventricular hypertrophy in genetically hypertensive rats.
MedLine Citation:
PMID:  18037780     Owner:  NLM     Status:  MEDLINE    
Beneficial effects of thiazolidinediones, peroxisome proliferator-activated receptor gamma (PPARgamma) agonists, on cardiovascular injuries have been reported. However, the effects of these agonists on left ventricular (LV) hypertrophy have not been clarified. To investigate whether pioglitazone improves LV hypertrophy, we used 32-week-old stroke-prone spontaneously hypertensive rats (SHR-SP) that had been treated or not treated with pioglitazone (10 mg/kg/day) for 8 weeks, and Wistar Kyoto rats (WKY). We evaluated LV geometry by echocardiography; myocyte hypertrophy, tissue fibrosis, and appearance of myofibroblasts by histological examination; mRNA expression by real-time polymerase chain reaction (PCR); protein expression by Western blot; activities of matrix metalloproteinase (MMP) by zymography; and production of reactive oxygen species (ROS) by electron spin resonance spectroscopy or thiobarbituric acid reactive substances (TBARS). SHR-SP showed concentric hypertrophy of the LV, but WKY did not. The myocyte diameter, fraction of tissue fibrosis, and number of myofibroblasts were greater in SHR-SP. mRNA expressions of collagen type I and type III, tissue growth factor (TGF)-beta1, and brain natriuretic peptide (BNP); protein expression of connective tissue growth factor (CTGF); activities of MMP2 and MMP9; and ROS were increased in SHR-SP. Pioglitazone did not decrease blood pressure, but partially normalized LV geometry in addition to decreasing myocyte diameter, interstitial fibrosis and number of myofibroblasts; mRNA levels of collagen type I and BNP; MMP2 activity; and protein level of CTGF. However, the mRNA level of collagen type III and TGF-beta1, MMP9 activity, and ROS production were not improved. In conclusion, pioglitazone reversed the concentric LV remodeling independently from blood pressure or oxidative stress in chronic hypertension.
Tomoko Shinzato; Yusuke Ohya; Minori Nakamoto; Akio Ishida; Shuichi Takishita
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Hypertension research : official journal of the Japanese Society of Hypertension     Volume:  30     ISSN:  0916-9636     ISO Abbreviation:  Hypertens. Res.     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-11-26     Completed Date:  2008-01-29     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9307690     Medline TA:  Hypertens Res     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  863-73     Citation Subset:  IM    
Department of Cardiovascular Medicine, Nephrology, and Neurology, School of Medicine, University of the Ryukyus, Okinawa, Japan.
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MeSH Terms
Blood Glucose / metabolism
Blood Pressure / drug effects
Collagen Type I / metabolism
Collagen Type III / metabolism
Connective Tissue Growth Factor
Hypertension / blood,  complications,  drug therapy*
Hypertrophy, Left Ventricular / drug therapy*,  etiology,  metabolism,  pathology
Hypoglycemic Agents / pharmacology,  therapeutic use*
Immediate-Early Proteins / metabolism
Insulin / blood
Intercellular Signaling Peptides and Proteins / metabolism
Matrix Metalloproteinases / metabolism
Natriuretic Peptide, Brain / metabolism
Organ Size / drug effects
PPAR gamma / metabolism
RNA, Messenger / metabolism
Rats, Inbred SHR
Rats, Inbred WKY
Reactive Oxygen Species / metabolism
Thiazolidinediones / pharmacology,  therapeutic use*
Transforming Growth Factor beta1 / metabolism
Reg. No./Substance:
0/Blood Glucose; 0/Collagen Type I; 0/Collagen Type III; 0/Ctgf protein, rat; 0/Hypoglycemic Agents; 0/Immediate-Early Proteins; 0/Intercellular Signaling Peptides and Proteins; 0/PPAR gamma; 0/RNA, Messenger; 0/Reactive Oxygen Species; 0/Thiazolidinediones; 0/Transforming Growth Factor beta1; 11061-68-0/Insulin; 111025-46-8/pioglitazone; 114471-18-0/Natriuretic Peptide, Brain; 139568-91-5/Connective Tissue Growth Factor; EC 3.4.24.-/Matrix Metalloproteinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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