Dynamic observation of mechanically-injured mouse femoral artery reveals an antiinflammatory effect of renin inhibitor.
OBJECTIVE
The renin-angiotensin-aldosterone system (RAS) plays a central role in atherosclerosis. To investigate the effects of a direct renin inhibitor aliskiren on vascular inflammation, we conducted leukocyte adhesion assays in vivo and in vitro using a novel real-time imaging system.


RESULTS
Aliskiren (10 mg/kg/d) or PBS was administered to C57BL/6 mice (6-7 weeks of age; Oriental Yeast, Tokyo, Japan) for 2 weeks via an osmotic pump. Blood pressure was not significantly changed in the 2 groups throughout the experimental period. A perivascular cuff injury was then introduced to the femoral artery and real-time intravital microscopic observation was conducted 24 hours after injury. The number of adherent leukocytes was elevated in the injured mice without aliskiren (43.8+/-9.3/10(-2) mm(2)), whereas that was significantly reduced in the mice with aliskiren (18.4+/-4.4, P<0.05). Treatment of human umbilical vein endothelial cells (HUVECs) with aliskiren significantly reduced the adhesion of THP-1 cells to TNF-alpha-activated HUVECs (P<0.05). Interestingly, TNF-alpha-induced renin activity and angiotensin II production in HUVECs were also blunted by aliskiren. Furthermore, exogenous renin and angiotensin II abrogated the aliskiren-mediated reduction of THP-1 cell adhesion to HUVECs.


CONCLUSIONS
Our in vivo and in vitro findings indicate a pivotal role for renin inhibition in vascular inflammation independent of blood pressure.
Life Science and Bioethics Research Center, Tokyo Medical and Dental University, Tokyo, Japan.
Jun
J
Ino
Chiari
C
Kojima
Mizuko
M
Osaka
Kosaku
K
Nitta
Masayuki
M
Yoshida
D000577:Amides / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D005263:Femoral Artery / Q000187:drug effects* / Q000293:injuries*; D005650:Fumarates / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000502:physiology; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000092502:Renin Inhibitors
D000577:Amides; D005650:Fumarates; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D000092502:Renin Inhibitors; C446481:aliskiren