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 cerebr al microvascular eicosanoid formation was assessed by means of bioassa y, radioimmunoassay and radio thin layer chromatography from endogenou s as well as from exogenous (20:4) radiolabelled substrate. The in vit ro as well as the in vivo (0.3 mg/kg/day for 1 week) effect of isradip ine was examined. Isradipine increased significantly (P < 0.01) both c onversion to and formation of PGI(2) and its derivative 6-oxo-PGF(1 al pha) respectively, as well as PGD(2)-production, while TXB2-synthesis was diminished. The conversion to the other metabolites was not affect ed to a significant extent. These findings indicate that isradipine en hances PGI(2)-generation in aorta and cerebral microvessels from both exogenous and endogenous substrate and PGD(2) from endogenous substrat e, a phenomenon shown to underlie the antiatherosclerotic actions of t his calcium channel blocker.