Abstract
We studied effect of chronic hypoxia (CH) on expression of platelet activating factor receptor (PAFR) by neonatal rats (pups). We hypothesized that PAFR antagonist will prevent pulmonary hypertension (PH) in pups exposed to CH. Pups were placed in an air-tight chamber ventilated with 13% oxygen, hypoxia (Hpx) or room air normoxia (Nmx) from 1d to 22d of age. Three groups of pups were studied (each group, n=10-14 pups): Group1, pups in Nmx; Group2, pups in Hpx given 5mg/kg PAFR receptor antagonist, WEB 2170, IP, every other day for 22d, (Hpx+WEB); Group3, pups in Hpx control. Hemotocrit, RV/LV+S, PAF binding, PAF synthesis, and PAFR expression were determined. Hyx control group had 2-fold higher RV/LV+S than Nmx group and PAFR antagonist decreased RV/LV+S to the Nmx control value. Lungs of pups in Hpx expressed more PAFR protein than Hpx+WEB and Nmx groups. Additionally, Hpx increased PAF synthesis and PAFR binding whereas WEB treatment decreased PAFR binding, but produced no difference in PAF synthesis compared to Nmx group. Hpx increased NF-kB p65 and TLR4 expression. WEB treatment abrogated expression or NF-kB p65 and TLR4 proteins. Our findings show that chronic hypoxia induces expression of PAFR, NF-kB p65 and TLR4 by pups’ lungs and suggest that increased PAFR expression may be responsible for the right ventricular hypertrophy and PH. Thus a PAFR antagonist may offer a therapeutic intervention for CH-induced PH in human neonates.