INTERACTIONS BETWEEN CYTOCHROME P-450 ACTIVITIES AND OZONE-INDUCED MODULATORY EFFECTS ON ENDOTHELIAL PERMEABILITY IN RABBIT LUNGS: Influence of Gender

Abstract

The effects of rabbit exposure to ozone (O3) (0.4 ppm for 4 h) on two different cytochrome P-450 (CYP450)-dependent activities were investigated. In turn, the role of CYP450 in the inhibitory effect of O 3 on acetylcholine (ACh)-evoked increase in endothelial permeability was also assessed. Immediately after the period of exposure, rabbits of both sexes were sacrificed and their lungs were extracted. Some lungs were used for preparation of microsomes and measurement of 7-ethoxyresorufin O -deethylase (EROD) and parathion oxidase activities. Other rabbit lungs were isolated and recirculatingly blood-free perfused. Arterial, venous pressures, and lung weight were continuously recorded. Capillary pressure was measured by applying the double occlusion method. Capillary filtration coefficient (K f,c) was evaluated by measuring the amount of fluid filtering through the endothelium when vascular pressures were suddenly increased. Dose-response curves to ACh were constructed in air- or O3-exposed rabbits. Some animals were pretreated with piperonyl butoxide (PBO), a well-known inhibitor of CYP450. O3 significantly reduced both EROD and parathion oxidase lung microsomal activities in females, while it had no effect in males. Exposure to O3 strongly inhibited the ACh-induced increase in K f,c. Pretreatment with PBO reversed the modulatory effect of O 3 on endothelial permeability in male rabbits, but not in females. It was concluded (1) that inhibition of 2 different CYP450-dependent activities after exposure to 0.4 ppm O3 for 4 h appears to be a gender-dependent phenomenon, and (2) that CYP450 is probably involved in the O 3-evoked inhibitory mechanism against ACh-induced increase in endothelial permeability, but only in males.