Increases in retinovascular prostaglandin receptor functions by cyclooxygenase-1 and -2 inhibition.

PURPOSE. TO determine the relative contribution of cyclooxygenase (COX)-1 and COX-2 in regulating prostaglandin (PG) E2 and PGF2a receptors (EP and FP, respectively) densities and their functions in retinal vasculature of neonatal pigs. METHODS. Newborn pigs were treated intravenously every 8 hours for 48 hours with saline, 40 mg/kg nonselective COX inhibitor ibuprofen, 80 mg/kg COX-1 inhibitor valeryl salicylate, or 5 mg/kg DuP697 and 5 mg/kg NS398, COX-2 inhibitors. Retinal microvessel EP and FP receptor densities were measured by radioligand binding and receptor-coupled effects by determining second-messenger inositol 1,4,5-trisphosphate (IP3) and vasomotor responses. Retinal blood flow (RBF) response to incremental increases in blood pressure (BP) was measured by a microsphere technique. RESULTS. Valeryl salicylate, DuP697, and NS398 reduced retinal PGE2 and PGF2Q. concentrations in the newborn by approximately half, whereas ibuprofen caused further reduction to levels observed in adults. Retinal vessel EP,, EP3, and FP receptor densities increased approximately threefold after treatments with COX-1 or COX-2 inhibitors, and five- to sixfold after ibuprofen treatment. EP and FP receptor upregulation was associated with corresponding increases in IP3 production and retinal vasoconstriction in response to PGF2a, fenprostalene (an FP agonist), PGE2, 17-phenyl trinor PGE2 (an EP, agonist), and MB the EP2 receptor was not significantly influenced by ontogenic alterations in prostaglandin levels. (Invest Ophthalmol Vis Sci. 1998;39:1888 -1898)