Interactions between cytochrome P-450 activities and ozone-induced modulatory effects on endothelial permeability in rabbit lungs: Influence of gender

The effects of rabbit exposure to ozone (O-3) (0.4 ppm for 4 h) on two diff erent 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. Immedia tely after the period of exposure, rabbits of both sexes were sacrificed an d their lungs were extracted. Some lungs were used for preparation of micro somes and measurement of 7-ethoxyresorufin O-deethylase (EROD) and parathio n oxidase activities. Other rabbit lungs were isolated and recirculatingly blood-free perfused. Arterial, venous pressures, and lung weight were conti nuously recorded. Capillary pressure was measured by applying the double oc clusion method. Capillary filtration coefficient (K-f,K-c) was evaluated by measuring the amount of fluid filtering through the endothelium when vascu lar pressures were suddenly increased. Dose-response curves to ACh were con structed in air- or O-3-exposed rabbits. Some animals were pretreated with piperonyl butoxide (PBO), a well-known inhibitor of CYP450. O-3 significant ly reduced both EROD and parathion oxidase lung microsomal activities in fe males, while it had no effect in males. Exposure to O-3 strongly inhibited the ACh-induced increase in K-f,K-c. Pretreatment with PBO reversed the mod ulatory effect of O-3 on endothelial permeability in male rabbits, but not in females. it was concluded (1) that inhibition of 2 different CYP450-depe ndent activities after exposure to 0.4 ppm O-3 for 4 h appears to be a gend er-dependent phenomenon, and (2) that CYP450 is probably involved in the O- 3-evoked inhibitory mechanism against ACh-induced increase in endothelial p ermeability, but only in males.