Developmental regulation of endothelial nitric oxide synthase in cerebral vessels of newborn pig by prostaglandin E-2

We investigated whether prostaglandins regulate endothelial nitric oxide sy nthase (eNOS) in the pig cerebral vasculature during the neonatal period. P rostaglandins, eNOS mRNA, eNOS protein, and NO production were higher in ce rebral microvessels of newborn (1 day old) than in those of adult (6- to 8- month-old) pigs. The treatment of isolated cerebral microvessels of newborn animals with ibuprofen for 24 h reduced eNOS mRNA and nitrite production t o levels in the adult; this effect of ibuprofen was prevented by concurrent treatment with prostaglandin (PG)E-2 analog 16,16-dimethyl-PGE(2), nonsele ctive PGE(2) receptor analog 11-deoxy PGE(1), and prostaglandin EP3 recepto r agonists sulprostone and M&B 28,767 but was not modified by PGI(2) analog carbaprostacyclin, PGD(2), and EP1 receptor agonist 17-phenyl trinor PGE(2 ). Correspondingly, 16,16-dimethyl-PGE(2) and M&B 28,767 increased eNOS mRN A expression of adult microvessels to values in the newborn. Data similar t o those with isolated cerebral vessels were obtained through histochemical analysis (NADPH-diaphorase positivity) of brain from newborn animals treate d in vivo with ibuprofen in combination or not with sulprostone. Furthermor e, substance P-induced NO-mediated cerebral vasorelaxation was decreased to adult values through the treatment of newborn pigs with ibuprofen; this ef fect was prevented by concomitant treatment with sulprostone. It is conclud ed that PGE2 regulates eNOS in newborn pig cerebral microvessels via EP3 re ceptors; this may be physiologically required during normal neurovascular d evelopment.