Interaction of Myeloperoxidase and Elastase Enzyme Activity with the Antihypertensive Agents Hydralazine and Dihydralazine

Abstract

Autoantibodies directed against myeloperoxidase and elastase have been found in patients developing hydralazine‐induced lupus and hydralazine‐induced isolated glomerulonephritis. The aim of this study was to investigate influence of hydralazine and dihydralazine upon myeloperoxidase and elastase enzyme activity. Using a 4‐aminoantipyrin in vitro system, dihydralazine was 2.5 times as potent in inhibiting myeloperoxidase activity as compared to hydralazine. The corresponding Ki‐values were 4 μmM for dihydralazine and 25 μM for hydralazine. When using 2.2′‐azino‐bis‐3‐ethylbenzothiazoline‐6‐sulphonic acid system inhibition was found at lower concentrations. Furthermore, the difference between the compounds was not so pronounced as seen for 4‐aminoantipyrin. The Ki‐values for hydralazine and dihydralazine were 1.2 and 1.4 μM respectively. Complete inhibition was seen for both compounds at concentrations above 7.5 μM. Hydralazine binds to elastase, but neither hydralazine nor dihydralazine inhibited elastase enzyme activity. 1993 Nordic Pharmacological Society