Document Detail

Angiotensin II type 1 receptor blocker attenuates myocardial remodeling and preserves diastolic function in diabetic heart.
MedLine Citation:
PMID:  17587756     Owner:  NLM     Status:  MEDLINE    
Blockade of the renin-angiotensin system reduces cardiovascular morbidity and mortality in diabetic patients. Angiotensin II (Ang II) plays an important role in the structural and functional abnormalities of the diabetic heart. We investigated whether or not Ang II type 1 receptor blocker (ARB) could attenuate left ventricular (LV) remodeling in male mice with diabetes mellitus (DM) induced by the injection of streptozotocin (200 mg/kg, i.p.). Diabetic mice were treated with candesartan (1 mg/kg/day; DM+Candesartan, n=7) or vehicle (DM+Vehicle, n=7) for 8 weeks. Heart rate and aortic blood pressure were comparable between the groups. Normal systolic function was preserved in diabetic mice. In contrast, diastolic function was impaired in DM+Vehicle and was improved in DM+Candesartan, as assessed by the deceleration time of the peak velocity of transmitral diastolic flow (40.3+/-0.3 vs. 37.3+/-0.5 ms, p<0.01) and the time needed for relaxation of 50% maximal LV pressure to baseline value (tau; 10.6+/-0.7 vs. 8.7+/-0.6 ms, p<0.05) without significant changes in heart rate and aortic blood pressure. Improvement of LV diastolic function was accompanied by the attenuation of myocyte hypertrophy, interstitial fibrosis and apoptosis in association with the expression of connective tissue growth factor (CTGF) and myocardial oxidative stress. Moreover, candesartan directly inhibited Ang II-mediated induction of CTGF in cultured cardiac fibroblasts. ARB might be beneficial to prevent cardiac abnormalities in DM.
Hiroyuki Tsutsui; Shouji Matsushima; Shintaro Kinugawa; Tomomi Ide; Naoki Inoue; Yukihiro Ohta; Takashi Yokota; Sanae Hamaguchi; Kenji Sunagawa
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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 May 
Date Detail:
Created Date:  2007-06-25     Completed Date:  2007-07-18     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  9307690     Medline TA:  Hypertens Res     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  439-49     Citation Subset:  IM    
Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
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MeSH Terms
Angiotensin II Type 1 Receptor Blockers / pharmacology*
Apoptosis / drug effects
Benzimidazoles / pharmacology*
Blood Glucose
Blood Pressure / drug effects
Body Weight
Cells, Cultured
Connective Tissue Growth Factor
Diabetes Complications / drug therapy*
Diabetes Mellitus, Experimental / complications*
Diastole / drug effects
Fibroblasts / cytology,  drug effects,  metabolism
Heart Failure / drug therapy*,  etiology,  ultrasonography
Heart Rate / drug effects
Immediate-Early Proteins / metabolism
Intercellular Signaling Peptides and Proteins / metabolism
Lipid Peroxidation / drug effects
Matrix Metalloproteinases / metabolism
Mice, Inbred Strains
Myoblasts, Cardiac / drug effects,  metabolism,  pathology
Tetrazoles / pharmacology*
Transforming Growth Factor beta / metabolism
Ventricular Function, Left / drug effects
Ventricular Remodeling / drug effects*
Reg. No./Substance:
0/Angiotensin II Type 1 Receptor Blockers; 0/Benzimidazoles; 0/Blood Glucose; 0/Ctgf protein, mouse; 0/Immediate-Early Proteins; 0/Intercellular Signaling Peptides and Proteins; 0/Tetrazoles; 0/Transforming Growth Factor beta; 139568-91-5/Connective Tissue Growth Factor; EC 3.4.24.-/Matrix Metalloproteinases; S8Q36MD2XX/candesartan

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