タイトル(掲載誌)Journal of Cardiovasc Pharmacol
一般注記The cardiac effects of calcium channel blockers(CCBs)related to cardiac remodeling are inconsistent. Matrix metalloprotein-ases(MMPs)contribute to tissue remodeling. Cardiac fibroblasts play an important role in the regulation of collagen degradation by MMPs. Using gelatin zymography, Western blotting, Griess reagent, and a calcium kit-fluo3, we investigated the effects of nifedipine, verapamil, diltiazem, and amlodipine on MMP-2 expression and fur-ther elucidate the mechanisms in cultured rat cardiac fibroblasts. Ni-fedipine increased and amlodipine decreased the expression of MMP-2; however, neither verapamil nor diltiazem altered MMP-2 expression. Nifedipine also increased nitrite production, and this in-crease was blunted by a nitric oxide(NO)synthases inhibitor(L-NAME).Nifedipine-induced MMP-2 expression was also blunted by L-NAME. An NO donor(sodiumnitroprusside)induced MMP-2 ex-pression. Data indicated that nifedipine might increase MMP-2 ex-pression through a possible NO-dependent pathway. Amlodipine had no influence on nitrite production. The amlodipine-induced decrease of MMP-2 expression was abolished by two protein tyrosine kinase inhibitors, genistein and herbimycin A, indicating that amlodipine might decrease MMP-2 expression through a possible protein tyro-sine kinase pathway. None of the four CCBs could alter the fluosce-nce intensity of fluo3, indicating that the effects of CCBs on MMP-2 expression were independent of the variation in intracellular Ca2+ concentration. Our findings revealed that different CCBs exerted dif-ferent effects on MMP-2 expression in cardiac fibroblasts.
一次資料へのリンクURLhttps://u-fukui.repo.nii.ac.jp/?action=repository_action_common_download&item_id=19956&item_no=1&attribute_id=22&file_no=1
連携機関・データベース国立情報学研究所 : 学術機関リポジトリデータベース(IRDB)(機関リポジトリ)