We have shown that COX inhibition of newborn pigs with the non-selective COX inhibitor, ibuprofen, up-regulates brain microvessel FP and EP (EP1 and EP3) receptor density and vasoconstriction to levels of adults. In the present study we investigated the relative contribution of COX-1 and COX-2 to this receptor up-regulation. Newborn (1 day old) pigs were treated either with the selective inhibitor of COX-1, valeryl salicylate (VSA, 80 mg/kg iv), or of COX-2 (DuP697 or NS398, 5 mg/kg iv), with ibuprofen (40 mg/kg iv), or with saline, every 8 h for 48 h. We then measured brain microvessel EP and FP receptor densities (Bmax, fmol/mg protein), receptor-coupled inositol 1,4,5-triphosphate (IP3) production and vasoconstriction (video imaging). DuP697 and NS398 (similar response to DuP697) increased newborn microvessel EP and FP receptor densities and maximal vasoconstriction (VC,% decrease in vessel diameter) in response to EP1, EP3 and FP agonists (17-phenyl trinor PGE2, M&B28,767 and PGF2ω, respectively) to a similar extent as ibuprofen (table); VSA had no effects. Corresponding changes in IP3 production were observed. Consistent with our recent report that COX-2 is the main source of prostaglandins in newborn brain, the present findings indicate that homologous regulation of EP and FP receptors and receptor-coupled function in brain microvasculature of the newborn is predominantly controlled by COX-2.
