Document Detail

Pulsatile mechanical pressure promotes Angiotensin-converting enzyme expression in aortic smooth muscle cells.
MedLine Citation:
PMID:  18679784     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Hypertension is a major risk factor for atherosclerosis, and elevated pressure (i.e., mechanical pressure stresses) has been known to modulate vascular remodeling, possibly by affecting the tissue renin-angiotensin system.
METHODS: In the present study we applied pulsatile pressure to human aortic smooth muscle cells (HASMCs) and investigated whether mechanical pressure stress affects cell proliferation and/or the angiotensin-converting enzyme (ACE), and we tested whether the administration of an angiotensin II (AII) receptor blocker has a favorable effect.
RESULTS: Three hours of pulsatile atmospheric pressure resulted in an approximately 8% increase in cell proliferation of human aortic smooth muscle cells. The cell surface ACE level, enzyme activity and mRNA expression were all elevated (37%, 110% and 17%, respectively) under pressurized conditions, and co-administration of AII reduced all these values. The reductions in these three parameters resulting from the administration of AII were all abolished by AII receptor blocker co-administration and values were increased (11%, 62% and 12%, respectively) under pressurized conditions. Pulsatile atmospheric pressure increased the amount of phosphorylated extracellular signal-regulated kinase (ERK) by approximately 54% in HASMCs. The administration of PD98059 (10 microM) resulted in a decrease in phosphorylated ERK and ACE activity in HASMCs compared to those of the pressurized control.
CONCLUSION: From these observations, we conclude that pulsatile mechanical pressure is one of the mediators of ACE production in vascular smooth muscle cells and that AII receptor blocking may prevent negative feedback. The present findings may provide a potential therapeutical target beyond lowering blood pressure in hypertensive patients.
Kenji Iizuka; Takuji Machida; Hideaki Kawaguchi; Masahiko Hirafuji
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Publication Detail:
Type:  Journal Article     Date:  2008-08-05
Journal Detail:
Title:  Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy     Volume:  22     ISSN:  0920-3206     ISO Abbreviation:  Cardiovasc Drugs Ther     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-09-05     Completed Date:  2009-01-12     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  8712220     Medline TA:  Cardiovasc Drugs Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  383-90     Citation Subset:  IM    
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan.
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MeSH Terms
Angiotensin II / pharmacology
Angiotensin Receptor Antagonists
Aorta / cytology
Atmospheric Pressure
Benzimidazoles / pharmacology
Captopril / pharmacology
Cell Line
Cell Proliferation / drug effects
Colorimetry / methods
Dose-Response Relationship, Drug
Extracellular Signal-Regulated MAP Kinases / metabolism
Flavonoids / pharmacology
Gene Expression Regulation, Enzymologic / drug effects
Membrane Proteins / genetics,  metabolism
Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors,  metabolism
Muscle, Smooth, Vascular / cytology,  drug effects,  metabolism*
Peptidyl-Dipeptidase A / genetics*,  metabolism*
Phosphorylation / drug effects
RNA, Messenger / genetics,  metabolism
Reverse Transcriptase Polymerase Chain Reaction
Stress, Mechanical
Tetrazoles / pharmacology
Time Factors
Reg. No./Substance:
0/2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; 0/Angiotensin Receptor Antagonists; 0/Benzimidazoles; 0/Flavonoids; 0/Membrane Proteins; 0/RNA, Messenger; 0/Tetrazoles; 11128-99-7/Angiotensin II; 62571-86-2/Captopril; EC Signal-Regulated MAP Kinases; EC Protein Kinase 1; EC A; S8Q36MD2XX/candesartan

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

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