M. Akishita et al., Angiotensin converting enzyme inhibitor restrains inflammation-induced vascular injury in mice, J HYPERTENS, 19(6), 2001, pp. 1083-1088
Citations number
28
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Objectives Recent advances in molecular genetics made the mouse model impor
tant for studying the genetic basis of hypertension and vascular diseases s
uch as the components of the renin-angiotensin system. This study was under
taken to investigate the role of angiotensin converting enzyme (ACE) in the
mouse vascular injury model.
Design and methods Inflammation-induced vascular injury was created by plac
ing a polyethylene cuff around the femoral artery of 12-14-week-old male FV
B/N mice. Cuffed arteries were harvested and applied to reverse transcripta
se-polymerase chain reaction analysis and immunohistochemistry for ACE. Sub
sequently, the effects of an ACE inhibitor, perindopril (3 mg/kg per day),
on neointimal thickening were examined 2 weeks after cuff placement. The in
fluence of a nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl es
ter (L-NAME, 20 mg/ kg per day) on the effects of perindopril was also exam
ined.
Results ACE mRNA expression increased in a time-dependent manner up to 2 we
eks after cuff placement. Immunoreactive ACE was localized in the endotheli
um in the intact artery, while positive staining was observed in the medial
and neointimal layer as well as in the periadventitial region of the cuffe
d artery. The intimamedia area ratio was significantly decreased by perindo
pril treatment (vehicle, 0.75 +/- 0.10; perindopril, 0.32 +/- 0.04; P < 0,0
5), The effect of perindopril was abrogated by coadministration of L-NAME w
hereas L-NAME alone did not affect the intima-media ratio (L-NAME, 0.66 +/-
0.11; perindopril + L-NAME, 0.72 +/- 0,09).
Conclusions This study provides evidence that ACE plays a role in cuff-indu
ced neointimal thickening in mice. Nitric oxide may contribute, at least in
part, to the inhibitory effects of perindopril.