title: Isradipine increases vascular prostaglandin I2-formation while the thromboxane B2-synthesis is diminished.
abstract: PGI2- and TXA2-synthesis from vascular tissue samples derived from cultured (endothelial and smooth muscle) cells, rabbit aorta and human bypass surgery were determined using specific radioimmunoassays for the stable derivatives (6-oxo-PGF1a and TXB2, respectively) of these compounds. Cultured cells were incubated in presence of isradipine, rabbits were pretreated for 4 weeks receiving 0.3 mg isradipine/kg*day, while patients were on isradipine (5-10 mg total dose/day, per os twice daily) since 6-19 weeks. In presence of isradipine, cultured cells produced significantly (p < 0.01) more 6-oxo-PGF1a and significantly less TXB2 (p < 0.05). 6-oxo-PGF1a-formation in rabbit aorta was significantly (p < 0.01) higher in isradipine treated normocholesterolemic animals while no significant changes were seen in isradipine treated hypercholesterolemic animals. TXB2 was significantly (p < 0.01) depressed in the abdominal and the thoracic aortic segment of isradipine treated hypercholesterolemic animals and was not significantly influenced in isradipine treated normocholesterolemic animals. Similarly, PGI2-synthesis in human arterial specimen was significantly (p < 0.01) enhanced as compared to the untreated controls. These findings indicate a beneficial behaviour of isradipine on vascular wall eicosanoid profile, which may contribute to a variety of antiatherosclerotic actions at the vascular wall level and to an improvement in hemostatic balance already described.
authors.affiliation: Wilhelm Auerswald Atherosclerosis Research Group (ASF), Vienna, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Kritz
authors.forename: P
authors.initials: P
authors.lastname: Schmid
authors.forename: A
authors.initials: A
authors.lastname: Keiler
authors.forename: J
authors.initials: J
authors.lastname: O'Grady
authors.forename: H
authors.initials: H
authors.lastname: Sinzinger
mesh_terms: D000368:Aged; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000819:agonists / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D017275:Isradipine / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D013552:Swine; D013556:Swine, Miniature; D013929:Thromboxane B2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
chemical_list: D002121:Calcium Channel Blockers; D013929:Thromboxane B2; D011464:Epoprostenol; D017275:Isradipine