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 PGI2 and its derivative 6-oxo-PGF1alpha respectively, as well as PGD2-production, while TXB2-synthesis was diminished. The conversion to the other metabolites was not affected to a significant extent. These findings indicate that isradipine enhances PGI2-generation in aorta and cerebral microvessels from both exogenous and endogenous substrate and PGD2 from endogenous substrate, a phenomenon shown to underlie the antiatherosclerotic actions of this calcium channel blocker.
Sinzinger
H
H
Wilhelm Auerswald Atherosclerosis Research Group (ASF) Vienna, Austria.
Wasinger
T
T
Böck
P
P
O'Grady
J
J
Peskar
B A
BA
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000187:drug effects; D016718:Arachidonic Acid / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002196:Capillaries / Q000166:cytology / Q000378:metabolism; D015777:Eicosanoids / Q000096:biosynthesis*; D011464:Epoprostenol / Q000096:biosynthesis / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D017275:Isradipine / Q000494:pharmacology*; D008297:Male; D008833:Microcirculation / Q000166:cytology / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D015230:Prostaglandin D2 / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013929:Thromboxane B2 / Q000096:biosynthesis
D002121:Calcium Channel Blockers; D015777:Eicosanoids; D005227:Fatty Acids; D016718:Arachidonic Acid; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D015230:Prostaglandin D2; D017275:Isradipine