Document Detail


Inhibition of experimental abdominal aortic aneurysm progression by nifedipine.
MedLine Citation:
PMID:  18204791     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Agents to inhibit the renin-angiotensin system have been reported to suppress the progression of abdominal aortic aneurysm (AAA). However, the effects of calcium channel blockers (CCBs) are still unclear in terms of the inhibition of the progression of AAA. Recently, several effects of CCBs beyond those associated with blood pressure lowering have attracted much interest. In this study, we examined the effects of nifedipine on AAA progression. AAA was induced in rats by transient aortic perfusion with elastase. Then, nifedipine (10 mg/kg/day) and saline (control) were administered to rats by osmotic mini-pump. At 2 and 4 weeks, the size of the AAA, blood pressure and heart rate were measured. Then, to further explore the mechanisms of the progression of AAA, we used human vascular smooth muscle cells (VSMCs). Especially, we focused on NF-kappaB and matrix metalloproteinase-9 (MMP-9). Treatment with nifedipine resulted in a significant inhibition of the progression of AAA such as aneurismal dilation at 14 and 28 days compared to the control (week 2: control, 2.98+/-0.71 mm; nifedipine, 2.37+/-0.64 mm; p<0.05 and week 4: control, 3.28+/-0.98 mm; nifedipine, 2.41+/-0.17 mm; p<0.05). Neither nifedipine nor saline changed blood pressure and heart rate, significantly. Nifedipine (1 microM) significantly suppressed angiotensin II-induced (10(-6) M) NF-kappaB activity in VSMCs by reporter assay (p<0.01). Furthermore, nifedipine (1 microM) inhibited MMP-9 protein expression and activity. Saline did not show such inhibitory effects. Taken together, these results indicated that nifedipine inhibits the progression of experimental AAA possibly through suppression of NF-kappaB and MMP-9 activity, leading to protective effects against AAA beyond those associated with blood pressure lowering.
Authors:
Naruya Tomita; Keita Yamasaki; Keiko Izawa; Yasuo Kunugiza; Mariana K Osako; Toshio Ogihara; Ryuichi Morishita
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of molecular medicine     Volume:  21     ISSN:  1107-3756     ISO Abbreviation:  Int. J. Mol. Med.     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-01-21     Completed Date:  2008-03-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9810955     Medline TA:  Int J Mol Med     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  239-44     Citation Subset:  IM    
Affiliation:
Division of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Suita 565-0871, Japan. tomita@med.kawasaki-m.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Animals
Aortic Aneurysm, Abdominal / drug therapy*,  pathology*,  physiopathology,  ultrasonography
Blood Pressure / drug effects
Blotting, Western
Calcium Channel Blockers / therapeutic use*
Cells, Cultured
Disease Models, Animal
Disease Progression
Electrophoretic Mobility Shift Assay
Heart Rate / drug effects
Humans
Male
NF-kappa B / genetics,  metabolism
Nifedipine / pharmacology,  therapeutic use*
Rats
Rats, Wistar
Sodium Chloride / pharmacology
Time Factors
Transcription, Genetic / drug effects
Chemical
Reg. No./Substance:
0/Calcium Channel Blockers; 0/NF-kappa B; 21829-25-4/Nifedipine; 7647-14-5/Sodium Chloride

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


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