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 th e proliferation of vascular smooth muscle cells (SMC) stimulated by foetal calf serum, basic fibroblast growth factor and platelet derived growth fact or, and in vivo with regard to SMC migration and proliferation which occurr ed following injury of the porcine carotid artery. The intimal lesion was i nduced 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 growt h factor-induced proliferation of SMC (0.20 < IC50 < 0.46 muM) In vivo, SR3 3805 reduced the intima/media ratio of the cross sectional surface area (de crease of 60%, P < 0.05) without affecting neointimal SMC density. The medi al SMC density was 40% lower in treated than in control animals (upstream, P < 0.05 acid downstream to the stenosis, P < 0.01). Thus, it appears that SR33805 significantly reduced intimal hyperplasia, which occurred after per ivascular manipulation of the artery, an effect consistent with its in vitr o proliferation inhibitory activity, suggesting that long-term treatment wi th SR33805 may reduce or delay SMC proliferation. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.