Platelet activating factor (PAF) receptor expression is increased in lungs of neonatal rats with hypoxia‐induced pulmonary hypertension

Abstract

Endogenous PAF contributes to high vasomotor tone in the fetal pulmonary circulation and has been implicated in the pathogenesis of chronic‐hypoxia (CH)‐induced pulmonary hypertension (PH). We studied the effect of CH on neonatal rat (pup) body weight, right ventricle/left ventricle + septum ratio (RV/LV+S), and lung PAF receptor (PAF‐r) protein expression by Western blotting. Pups were placed in an air‐tight chamber ventilated with 13% oxygen (hypoxia) or room air (normoxia) from 1d to 22d of age. Three groups were studied (12 pups in each group): Group1, pups in Hypoxia; Group2, pups in hypoxia given 5mg/kg WEB 2170 daily, a PAF‐r antagonist, (Hypoxia +WEB); Group3, pups in Normoxia. We found that: a) Pups in Hypoxia gained 50% less weight than pups in Normoxia; WEB treatment in Hypoxia did not improve weight gain; b) RV/LV+S in Hypoxia group was highest at 0.79; 2‐fold higher than in WEB + Hypoxia and Normoxia groups; c) PAF‐r protein expression in lungs of pups in Hypoxia was >3‐fold higher than in WEB+Hypoxia and Normoxia groups. Our findings show that chronic hypoxia induces PAF‐r expression in lungs and suggest that increased PAF‐r expression may be responsible for the right ventricular hypertrophy and PH. Inhibition of PAF effects with a PAF‐r antagonist, WEB, though it did not improve weight gain of the pups in hypoxia, prevented RV hypertrophy in the pups. HL‐077819.