P. Fitscha et al., ISRADIPINE INHIBITS MITOTIC AND PROLIFERATIVE ACTIVITY IN THE ARTERIAL NAIL, Experimental and toxicologic pathology, 46(1), 1994, pp. 75-80
The anti-mitotic (H-3-thymidine uptake quantified using autoradiograph
y) and anti-proliferative (counting of activated smooth muscle cells o
n semithin sections) effects of the dihydropyridine calcium channel bl
ocker isradipine (0.3 mg/kg) have been assessed in a rabbit arterial s
tress model. Isradipine caused a significant drop in both mitotic and
proliferative activity. These effects were more pronounced by pretreat
ment (6 hours before lesion induction with desoxycorticosterone) with
isradipine as compared to posttreatment (6 hours after experimental le
sioning). The benefit induced by isradipine was abolished by aspirin t
reatment. In-vitro vascular prostacyclin formation and cholesterol con
tent were not affected. These findings suggest that the anti-atheroscl
erotic action of isradipine on mitotic activity and cellular prolifera
tion is mediated by a cyclooxygenase product, most likely via enhanced
local vascular PGI(2)-synthesis.