Alteration of rat cerebral microvascular eicosanoid formation by isradipine, a calcium channel blocker

We studied the influence of the calcium channel blocker isradipine on cerebral microvascular and aortic eicosanoid synthesis. The rat cerebral microvascular eicosanoid formation was assessed by means of bioassay, radioimmunoassay and radio thin layer chromatography from endogenous as well as from exogenous (20:4) radiolabelled substrate. The in vitro as well as the in vivo (0.3 mg/kg/day for 1 week) effect of isradipine was examined. Isradipine increased significantly ( P < 0.01) both conversion to and formation of PGI 2 and its derivative 6-oxo-PGF 1α, respectively, as well as PGD 2-production, while TXB 2-synthesis was diminished. The conversion to the other metabolites was not affected to a significant extent. These findings indicate that isradipine enhances PGI 2-generation in aorta and cerebral microvessels from both exogenous and endogenous substrate and PGD 2 from endogenous substrate, a phenomenon shown to underlie the antiatherosclerotic actions of this calcium channel blocker.