CAPTOPRIL INHIBITS THE 72-KDA AND 92-KDA MATRIX METALLOPROTEINASES

Gelatinases are metalloproteinases in the kidney which can cleave type IV collagen as well as gelatin. We partially purified the 72 kDa and 92 kDa gelatinases. The gelatinolytic activity was measured by zymogra phy and a quantitative biotin-avidin assay. By zymography, captopril i n concentrations of 20 mm and 40 mm added to the incubation buffer red uced the gelatinolytic activity in a dose-dependent manner. The additi on of zinc in a concentration of 50 to 100 mum reversed most of the in hibitory effect of captopril. By the biotin-avidin assay, captopril in a concentration of 30 to 50 nm reduced half of either the 72 kDa or 9 2 kDa gelatinolytic activity. Zinc in a concentration of 50 mum comple tely reversed the inhibitory effect of i mum captopril on both gelatin ases. Lisinopril, a non-sulfhydryl ACE inhibitor, similarly inhibited the gelatinases, but a 1000-fold higher concentration of the drug was needed. These findings suggest that captopril reversibly inhibits the 72 kDa and 92 kDa metalloproteinases by interacting with the zinc ion at their active sites. This inhibitory effect is observed with captopr il levels comparable to the concentrations needed to inhibit the angio tensin converting enzyme in vivo and may at least partially explain so me of the renoprotective effects seen with this drug.