title: Pulsatile mechanical pressure promotes Angiotensin-converting enzyme expression in aortic smooth muscle cells.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan. kiizuka@hoku-iryo-u.ac.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Iizuka
authors.forename: Takuji
authors.initials: T
authors.lastname: Machida
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kawaguchi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hirafuji
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D001011:Aorta / Q000166:cytology; D001274:Atmospheric Pressure; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D002216:Captopril / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003124:Colorimetry / Q000379:methods; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics* / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013314:Stress, Mechanical; D013777:Tetrazoles / Q000494:pharmacology; D013997:Time Factors
chemical_list: D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D005419:Flavonoids; D008565:Membrane Proteins; D012333:RNA, Messenger; D013777:Tetrazoles; D000804:Angiotensin II; D002216:Captopril; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D007703:Peptidyl-Dipeptidase A; C081643:candesartan; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one