Isradipine inhibits mitotic and proliferative activity in the arterial wall.
The anti-mitotic (3H-thymidine uptake quantified using autoradiography) and anti-proliferative (counting of activated smooth muscle cells on semithin sections) effects of the dihydropyridine calcium channel blocker isradipine (0.3 mg/kg) have been assessed in a rabbit arterial stress model. Isradipine caused a significant drop in both mitotic and proliferative activity. These effects were more pronounced by pretreatment (6 hours before lesion induction with desoxycorticosterone) with isradipine as compared to posttreatment (6 hours after experimental lesioning). The benefit induced by isradipine was abolished by aspirin treatment. In-vitro vascular prostacyclin formation and cholesterol content were not affected. These findings suggest that the anti-atherosclerotic action of isradipine on mitotic activity and cellular proliferation is mediated by a cyclooxygenase product, most likely via enhanced local vascular PGI2-synthesis.
Fitscha
P
P
2nd Department of Internal Medicine, Policlinic Vienna, Austria.
Rauscha
F
F
O'Grady
J
J
Keiler
A
A
Sinzinger
H
H
D000818:Animals; D001158:Arteries / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D003900:Desoxycorticosterone / Q000031:analogs & derivatives / Q000494:pharmacology; D011464:Epoprostenol / Q000096:biosynthesis; D006801:Humans; D017275:Isradipine / Q000494:pharmacology*; D008297:Male; D008938:Mitosis / Q000187:drug effects*; D011817:Rabbits; D013936:Thymidine / Q000493:pharmacokinetics
C019323:deoxycortone pivalate; D003900:Desoxycorticosterone; D002784:Cholesterol; D011464:Epoprostenol; D001241:Aspirin; D013936:Thymidine; D017275:Isradipine