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Captopril and Lisinopril Only Inhibit Matrix Metalloproteinase‐2 ( MMP ‐2) Activity at Millimolar Concentrations
Author(s) -
Kuntze Luciana B.,
Antonio Raquel C.,
IzidoroToledo Tatiane C.,
Meschiari Cesar A.,
TanusSantos Jose E.,
Gerlach Raquel F.
Publication year - 2014
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12151
Subject(s) - captopril , lisinopril , chemistry , zymography , matrix metalloproteinase , enzyme , angiotensin converting enzyme , chromatography , pharmacology , biochemistry , endocrinology , medicine , blood pressure
Matrix metalloproteinase‐2 ( MMP ‐2) shares structural similarities with the angiotensin‐converting enzyme ( ACE ). ACE inhibitors have been described to inhibit MMP ‐2, but this inhibitory potential was not shown using a highly purified MMP ‐2. This study aimed to investigate the inhibitory potential of captopril and lisinopril regarding MMP ‐2 activity. The first objective was to test the potential of captopril to change the pH of the buffer solution. The second objective was to test the direct inhibitory effect of captopril and lisinopril on plasma MMP ‐2 and on recombinant human MMP ‐2 (rh MMP ‐2). The in vitro activity assays included gelatin zymography and a fluorimetric assay. Captopril solubilization significantly decreased the pH of the 50 mM Tris buffer solution at the following concentrations: 2 mM ( p < 0.05), 4 mM and 8 mM ( p < 0.01), while only the 8 mM lisinopril induced a drop in pH ( p < 0.05). Thus, only 200 mM buffer solutions were used. Zymography results of plasma MMP ‐2 and rh MMP ‐2 showed that inhibition only happened at captopril concentrations ≥ 4 and 1 mM, respectively ( p < 0.05), while only the higher concentration of lisinopril (8 mM) inhibited plasma MMP ‐2 ( p < 0.05). In the fluorimetric assay, captopril led to significant inhibition of the rhMMP‐2 activity at concentrations ≥2 mM ( p < 0.01), whereas aminophenylmercuric acetate‐activated rh MMP ‐2 was inhibited by 0.5 mM captopril ( p < 0.01). The captopril and lisinopril concentrations found to inhibit MMP‐2 are 3 orders of magnitude higher than those present in vivo after drug administration. We also discuss possible pitfalls for gelatinase inhibitory assays (besides the obvious pH problem already cited). In conclusion, this study's data show that captopril and lisinopril did not inhibit MMP ‐2 directly at the concentrations reached in vivo .