Beneficial effects of pioglitazone on left ventricular hypertrophy in genetically hypertensive rats.
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.
Department of Cardiovascular Medicine, Nephrology, and Neurology, School of Medicine, University of the Ryukyus, Okinawa, Japan.
Tomoko
T
Shinzato
Yusuke
Y
Ohya
Minori
M
Nakamoto
Akio
A
Ishida
Shuichi
S
Takishita
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D055513:Connective Tissue Growth Factor; D004452:Echocardiography; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017874:Immediate-Early Proteins / Q000378:metabolism; D007328:Insulin / Q000097:blood; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D047495:PPAR gamma / Q000378:metabolism; D000077205:Pioglitazone; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017382:Reactive Oxygen Species / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D001786:Blood Glucose; C526316:CCN2 protein, rat; D024042:Collagen Type I; D024061:Collagen Type III; D007004:Hypoglycemic Agents; D017874:Immediate-Early Proteins; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D047495:PPAR gamma; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D045162:Thiazolidinediones; D053773:Transforming Growth Factor beta1; D020097:Natriuretic Peptide, Brain; D055513:Connective Tissue Growth Factor; D020782:Matrix Metalloproteinases; D000077205:Pioglitazone