Biosynthesis of Prostacyclin in Rat Cerebral Microvessels and the Choroid Plexus

Abstract

Microvessels, predominantly capillaries, were isolated from rat cerebrum by a modification of published procedures. The morphology and purity of the preparations were monitored by light microscopy and by enrichment in alkaline phosphatase, .gamma.-glutamyl transpeptidase and prostacyclin synthetase. A reversed-phase high-pressure liquid chromatographic method was used in the purification of prostaglandins [PG] after extraction from aqueous incubation solutions. Prostacyclin synthesis in brain is localized in cerebral blood vessels and capillaries. The endogenous biosynthetic capacity of the isolated cerebral capillary fractions for prostacyclin, measured as its chemically stable breakdown product, 6-keto-PGF1.alpha., was 11 ng/mg protein per 10 min. Choroid plexus and intact surface vessels synthesized 6-keto-PGF1.alpha. at 37 and 35 ng/mg protein per 10 min, respectively. The prostacyclin-synthesizing enzyme of the cerebral capillaries also converted the exogenously added PG endoperoxides to 6-keto-PGF1.alpha.. Comparison of the synthesis of 6-keto-PGF1.alpha., PGE2 and PGF2.alpha. showed that 6-keto-PGF1.alpha. was the major PG formed in the microvessels, in the larger surface vessels and in the choroid plexus. PGD2 was not detected. Prostacyclin synthesis by the crebral vasculature is similar to that in other blood vessels and cultured human endothelial cells. Possible physiological roles of prostacyclin in the cerebral microvasculature are discussed with special regard to the autoregulation of cerebral blood flow.