Effects on Arterial Hypertension of Heat-inactivated Tyrosinase Preparations. ∗

Abstract

Recent studies of the mechanisms involved in the production of experimental renal hypertension show that several humoral agents may be involved. Following the hypothesis that phenolic amines may be involved in renal hypertension, Schroeder and Adams 1 found tyrosinase preparations from mushrooms to be effective in lowering the blood pressures of hypertensive animals. Their studies were extended to the effects of tyrosinase preparations on arterial hypertension in man and reported results in 17 patients, with significant falls in blood pressures in 13 of these following daily administration of unspecified amounts of their tyrosinase preparations. Some phenolic substance was considered to be altered by the injected enzyme to account for the lowered blood pressures observed.

The present experiments were carried out with mushroom tyro-sinase preparations made by modifications of the purification procedures of Keilin and Mann. 3 The valuation of the enzymic activity was made upon a catechol-hydroquinone substrate in terms of “catecholase” units as defined by Adams and Nelson. 4 The final preparations were made up to contain 500 “catecholase” units per ml and contained about 2 mg per ml of non-dialyzable total solids. By heating such preparations for 40 minutes to 60°C, about 95% of the “catecholase” activity was destroyed, and such preparations are referred to as heat-inactivated.

Four patients with malignant or premalignant hypertension were hospitalized and observed before treatment for 7 to 10 days, with blood pressures taken twice or more daily. In the first patient studied, the marked local reactions from injections of the unheated enzyme preparations suggested that the hypotensive response might be due to non-enzymic substances in the preparation. Treatment was then continued with heat-inactivated preparations and it was observed that, while the enzymic activity was almost completely absent and the local reactions were somewhat less, these preparations were still very effective in lowering blood pressure.