Lung strips from guinea pigs as test system for lipoxygenase inhibitors. Inhibition of arachidonic acid-induced contractions by 3-t-butyl-4-hydroxyanisole and nordihydroguaiaretic acid.

Lung strips and tracheal spirals from guinea pigs and rats were compared as test systems for lipoxygenase inhibitors. The contraction of the smooth muscle was induced by addition of arachidonic acid. Lung strips of guinea pigs proved to be the most suitable in vitro model. Under basal conditions half-maximal contraction was produced by 13 microM arachidonic acid (AA) which was strongly inhibited by 50 microM nordihydroguaiaretic acid (NDGA) or 100 microM 3-t-butyl-4-hydroxyanisole (BHA). NDGA and BHA caused a shift of response towards higher concentrations of AA. BHA also produced pronounced dilatations of both basal tonus and carbachol-induced contractions of the preparations from the respiratory tract. It is concluded that the actions of NDGA and BHA on the airway preparations are due to inhibition of the lipoxygenase reaction and, therefore, of leukotriene synthesis. The assumption of the lipoxygenase inhibition is supported by their action on purified lipoxygenase from rabbit reticulocytes which was inhibited by 50% by 0.5 microM NDGA and 160 microM BHA. In contrast, the antioxidant 2,6-di-t-butyl-4-hydroxytoluene (BHT) did not inhibit at all at 1 mM. To the knowledge of the authors this is the first evidence so far reported for the bronchodilating action of BHA.