Lung mitochondrial dysfunction in pulmonary hypertension syndrome. I. Site-specific defects in the electron transport chain

The main objectives of this study were to determine a) site-specific defect s in the electron transport chain of lung mitochondria of broilers with pul monary hypertension syndrome (PHS), b) if these defects are attenuated by h igh dietary vitamin E, and c) if these defects have a genetic basis. In Exp eriment 1, lung mitochondria were isolated from broilers with and without P HS fed diets containing 15 IU and 100 IU dl-alpha -tocopherol acetate/kg (V E); the four treatments were control, VE, PHS, and VE-PHS, respectively. Hy drogen peroxide (H2O2) generation in isolated lung mitochondria was monitor ed by dichlorofluorosein (DCF) fluorescence in response to chemicals that i nhibit electron flow at specific sites on the electron transport chain usin g a 96-well microplate with Cytoflour (excitation/emission 480/530 nm). Bas al H2O2 production was higher in PHS than in control mitochondria. Differen ces in H2O2 production between control and PHS were magnified by inhibition of Complexes I and III (Coenzyme Q) of the respiratory chain in mitochondr ia. Functional defects in PHS mitochondria were attenuated by high dietary VE. Ln Experiment 2, basal H2O2 production and that following inhibition of Complexes I and III were lower in lung mitochondria isolated from broilers selected for genetic resistance to PHS than in nonselected birds in the ba se population. The results of this study indicate that site-specific defect s in Complexes I and III may underlie lung mitochondrial dysfunction in bro ilers with PHS, that these defects are attenuated by high dietary vitamin E , and that these defects may be related to genetic predisposition to PHS.