The calcium inhibitor SR33805 reduces intimal formation following injury of the porcine carotid artery.
We studied the effect of SR33805, a calcium channel blocker, in vitro on the proliferation of vascular smooth muscle cells (SMC) stimulated by foetal calf serum, basic fibroblast growth factor and platelet derived growth factor, and in vivo with regard to SMC migration and proliferation which occurred following injury of the porcine carotid artery. The intimal lesion was induced by a silasten collar surgically positioned around the carotid artery and by a stenosis reducing blood flow by 50% for 30 days. Animals received SR33805 (5 mg/kg/day) 8 days before the induction of the lesion and up to 30 days after. In vitro, SR33805 inhibited in a dose-dependent manner growth factor-induced proliferation of SMC (0.20<IC(50)<0.46 microM). In vivo, SR33805 reduced the intima/media ratio of the cross sectional surface area (decrease of 60%, P<0.05) without affecting neointimal SMC density. The medial SMC density was 40% lower in treated than in control animals (upstream, P<0.05 and downstream to the stenosis, P<0.01). Thus, it appears that SR33805 significantly reduced intimal hyperplasia, which occurred after perivascular manipulation of the artery, an effect consistent with its in vitro proliferation inhibitory activity, suggesting that long-term treatment with SR33805 may reduce or delay SMC proliferation.
Hainaud
P
P
Institut des Vaisseaux et du Sang, Hôpital Lariboisière, 8 rue Guy Patin, 75475 Cedex 10, Paris, France.
Bonneau
M
M
Pignaud
G
G
Bal dit Sollier
C
C
André
P
P
Hadjiisky
P
P
Fieffé
J P
JP
Caen
J P
JP
Herbert
J M
JM
Dol
F
F
Drouet
L O
LO
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000473:pathology / Q000517:prevention & control; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020212:Carotid Artery Injuries; D017536:Carotid Artery, Common / Q000187:drug effects / Q000473:pathology*; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D018715:Microscopy, Video; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D013450:Sulfones / Q000494:pharmacology*; D013552:Swine; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology*
D002121:Calcium Channel Blockers; D007211:Indoles; D013450:Sulfones; C084255:SR 33805