[Changes of MMP-2,9 and TIMP-1 expressions in rats with pulmonary arterial hypertension after captopril and losartan interventions].

Abstract

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.

CONCLUSION:

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.

• Authors: Xian-min Wang, Tong-fu Zhou, Bin Liu, Li Wei, Kun Shi, Shan-shan Zhao, Yi-min Hua, Han-ming Liu
• Journal: Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition (Sichuan Da Xue Xue Bao Yi Xue Ban) Vol. 40 Issue 2 Pg. 255-9 (Mar 2009) ISSN: 1672-173X [Print] China
• PMID: 19462901 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Messenger
• Tissue Inhibitor of Metalloproteinase-1
• Captopril
• Matrix Metalloproteinase 2
• Mmp2 protein, rat
• Matrix Metalloproteinase 9
• Losartan

Topics

• Animals
• Captopril (therapeutic use)
• Hypertension, Pulmonary (drug therapy, metabolism)
• Losartan (therapeutic use)
• Male
• Matrix Metalloproteinase 2 (genetics, metabolism)
• Matrix Metalloproteinase 9 (genetics, metabolism)
• RNA, Messenger (genetics, metabolism)
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Tissue Inhibitor of Metalloproteinase-1 (genetics, metabolism)