PROSTANOID SYNTHESIS IN RESPONSE TO HIGH CO2 IN NEWBORN PIG BRAIN MICROVASCULAR ENDOTHELIAL-CELLS

Hypercapnia-induced cerebral vasodilation involves prostanoids in newb orn pigs. However, the source of prostanoids has not been determined. The current study was designed to address the hypothesis that piglet c erebral microvascular endothelial cells increase their synthesis of pr ostanoids in response to high CO2. Microvascular endothelial cells, sm ooth muscle cells, and glia were isolated and grown in primary culture . They were identified morphologically and by indirect immunofluoresce nce staining. Cerebral microvascular endothelial cell cultures from ne wborn pigs produced equal amounts of 6-ketoprostaglandin (PG) F1alpha (stable hydrolysis product of PGI2) PGE2 and a small amount of PGF2alp ha under basal conditions. Administration of calcium ionophore A23187 to the endothelial cells increased release of all three prostanoids in a dose- and time-dependent manner. Exposure of piglet cerebral microv ascular endothelial cells to higher than normal CO2 increased the prod uction of 6-keto-PGF1alpha and PGE2 but not of PGF2alpha. The enhanced prostanoid biosynthesis was concentration dependent, peaking at 14% C O2, and was detected during the first 10 min exposure to 14% CO2. Hype rcapnia-induced increased synthesis of prostanoids was blocked dose de pendently by the simultaneous addition of PGH synthase inhibitor indom ethacin. High CO2 did not increase prostanoid production by cerebral m icrovascular smooth muscle cells or glia, although A23187 enhanced pro stanoid formation by both cell types. These data show that high CO2 st imulates prostanoid synthesis by newborn pig cerebral microvascular en dothelial cells, which is consistent with an involvement of cerebral v ascular endothelium in hypercapnia-induced vasodilation.