Losartan inhibited expression of matrix metalloproteinases in rat atherosclerotic lesions and angiot

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:candry
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AIM: To explore whether the angiotensin Ⅱ (Ang Ⅱ) receptor 1 (AT1) antagonist, losartan could reduce activity and expression of matrix metalloproteinases (MMPs) in rat atherosclerotic plaques. METHODS: Male Wistar-Kyoto rats were ip injected a single dose of vitamin D3 600 kU·kg-1·month-1 and fed an atherogenic diet for 4 months to induce experimental atheroma. Then either placebo or losartan 50 mg·kg-1·d-1 was administered in rats for another 2 months. In vitro, the effect of losartan 0.1-10μmol/L on the expression of MMP-2 and MMP-9 was investigated in Ang II-stimulated rat peritoneal macrophages. The expression and activity of MMP-2 and MMP-9 were monitored by Western blot, RT-PCR, and SDS-PAGE zymography analysis. RESULTS: High levels of MMP-2 and MMP-9 were expressed in rat atherosclerotic lesions. Losartan significantly reduced the activity and expression of MMP-2 and MMP-9 compared with the placebo group (MMP-2, 5861±539 vs 8991±965, P<0.05; MMP-9, 10527±1002 vs 14623±2462, P<0.01). In AIM: To explore whether the angiotensin II (Ang II) receptor 1 (AT1) antagonist, losartan could reduce activity and expression of matrix metalloproteinases (MMPs) in rat atherosclerotic plaques. METHODS: Male Wistar-Kyoto rats were ip injected a single dose of vitamin D3 600 kU · kg-1 · month-1 and fed an atherogenic diet for 4 months to induce atheroma. Then either placebo or losartan 50 mg · kg-1 · d-1 was administered in rats for another 2 months. In The effect of losartan 0.1-10 μmol / L on the expression of MMP-2 and MMP-9 was investigated in Ang II-stimulated rat peritoneal macrophages. The expression and activity of MMP-2 and MMP-9 were monitored by Western blot RESULTS: High levels of MMP-2 and MMP-9 were expressed in rat atherosclerotic lesions. Losartan significantly reduced the activity and expression of MMP-2 and MMP-9 compared with the placebo group (MMP-2, 5861 ± 539 vs 8991 ± 965, P <0.05; MMP-9, 10527 ± 1002 vs 1462 3 ± 2462, P <0.01)
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