Document Detail


Fibrotic response to angiotensin II is blunted in the kidney, but not in the heart, in insulin-sensitive long-lived transgenic dwarf rats.
MedLine Citation:
PMID:  17143544     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Insulin resistance is a characteristic feature of cardiovascular and renal diseases, and angiotensin II (Ang II) has been suggested to induce insulin resistance. The aims of this study were to elucidate the effect of chronic Ang II infusion on vascular reactivity and organ damage in insulin-sensitive rats. We confirmed the following three points. First, there was no significant difference in pressor response to chronic Ang II infusion (600 ng/kg/min) between insulin-sensitive transgenic rats (Tg) and control rats (C). Second, there was no significant difference in cardiac hypertrophy and fibrosis by chronic Ang II infusion between the two groups. However, third, fibrotic response to chronic Ang II infusion evaluated by histopathological scoring in the kidney was significantly decreased in insulin-sensitive transgenic rats (renal fibrosis and nephropathy score: C+Ang II vs Tg+Ang II; 2.5 vs 1.3; p<0.05). Furthermore, the expression of TGF-beta, a fibrosis indicator, was also significantly suppressed in the kidneys of the transgenic rats (TGF-beta1/GAPDH ratio: C+Ang II vs Tg+Ang II; 1.15 vs 0.81; p<0.05). This result indicates that the growth hormone/insulin-like growth factor-1 axis is critically involved in the development of renal injury and fibrosis, rather than hypertension, cardiac hypertrophy, and cardiac fibrosis induced by chronic Ang II administration.
Authors:
Osami Sato; Naoto Ashizawa; Akira Ohtsuru; Ryo Imanishi; Hiroaki Kawano; Shinji Seto; Shunichi Yamashita; Isao Shimokawa; Katsusuke Yano
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  International journal of molecular medicine     Volume:  19     ISSN:  1107-3756     ISO Abbreviation:  Int. J. Mol. Med.     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2006-12-04     Completed Date:  2007-03-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9810955     Medline TA:  Int J Mol Med     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  23-7     Citation Subset:  IM    
Affiliation:
Division of Cardiovascular Medicine, Course of Medical and Dental Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
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MeSH Terms
Descriptor/Qualifier:
Angiotensin II / administration & dosage*
Animals
Animals, Genetically Modified
Body Weight / drug effects
Dwarfism
Echocardiography
Fibrosis / etiology*,  metabolism
Heart Rate / drug effects
Infusions, Intravenous
Insulin / pharmacology
Insulin-Like Growth Factor I / analysis
Kidney / drug effects,  metabolism,  pathology*
Male
Myocardium / pathology*
Organ Specificity
RNA, Messenger / metabolism
Rats
Rats, Wistar
Transforming Growth Factor beta1 / metabolism
Chemical
Reg. No./Substance:
0/RNA, Messenger; 0/Transforming Growth Factor beta1; 11061-68-0/Insulin; 11128-99-7/Angiotensin II; 67763-96-6/Insulin-Like Growth Factor I

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