[Changes of MMP-2,9 and TIMP-1 expressions in rats with pulmonary arterial hypertension after captopril and losartan interventions].
OBJECTIVE
To determine the effect of captopril and losartan on the expressions of matrix metalloproteinase-2,9 (MMP-2,9) and metalloproteinase-1 (TIMP-1) in rats with pulmonary arterial hypertension, and the mechanisms of captopril and losartan in intervening the development of pulmonary arterial hypertension.


METHODS
Forty male Spraque-Dawley rats were divided into 4 groups randomly: pulmonary arterial hypertension (created by pneumonectomy plus MCT injection) model group (PAH Model), PAH model treated with captopril [PAH+Cap 10 mg/(kg x d)], losartan group [PAH+Los 15 mg/(kg x d)] and normal control group(Control). The mPAP, weight ratio of RV to LV+S, neointima formation, relative thickness of small pulmonary arteries, and degree of muscularization of non-muscular arterioles were measured at day 35. The expression of SM-a-actin in the PASMC was determined by immunochemistry stain. The expressions of MMP-2, 9, TIMP-1 and MMP-2, 9, TIMP-1 mRNA in the pulmonary tissues were determined by immunohistochemistry and FQ-PCR respectively. The enzymatic activity of MMP-2, 9 was measured by Gelatin zymography.


RESULTS
Pneumonectomy plus MCT injection induced severe pulmonary arterial hypertension characterized by neointimal formation. Captopril or losartan suppressed the increase of mPAP, right ventricle weight, thickness of small pulmonary arteries and muscularization of peripheral pulmonary arterioles in the rats with PAH (P < 0.05). The PAH model group had higher expressions of MMP-2, 9, TIMP-1 mRNA and enzymatic activity of MMP-2, 9 in lung tissue than the other groups (P < 0.05). Captopril intervention had similar effects as losartan intervention.


CONCLUSIONS
The captopril and losartan induced attenuation of PAH and pulmonary vascular remodeling is likely to be associated with the regulation of the expressions of MMP-2, 9, TIMP-1.
Wang
Xian-min
XM
Department of Padiatric Cardiology, West China Second Hospital, Sichuan University, Chengdu 610041, China.
Zhou
Tong-fu
TF
Liu
Bin
B
Wei
Li
L
Shi
Kun
K
Zhao
Shan-shan
SS
Hua
Yi-min
YM
Liu
Han-ming
HM
D000818:Animals; D002216:Captopril / Q000627:therapeutic use*; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000378:metabolism; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D002216:Captopril; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; D019808:Losartan