Flunarizine, cerebral blood flow and reversion of experimental atherosclerosis in rabbit

Flunarizine is a calcium entry blocker active in the treatment of peripheral vascular disease. The present study was performed to evaluate the effect of flunarizine on cerebral blood flow (CBF) and lipidic patterns in rabbits with dietary experimental atherosclerosis. Since it is well known that there is only a slight correlation between the severity of atheromatous lesions ascertained at necroscopy and the severity of clinical symptoms of cerebral vascular disease, the effect of the drug was assessed by measuring the CBF and compartmental distribution of blood flow in unanaesthetized rabbits by the intracarotid Xe-133 clearance method; blood pressure, plasma lipids and tissue fat infiltration were also checked. An atherogenic diet brings about significant impairment of CBF. Flunarizine is inactive in normal rabbits if chronically administered at the daily dose of 10 mg/kg p.o. In atherosclerotic rabbits chronic treatment with flunarizine induced a pronounced increase in cerebral haemodynamic parameters. Arterial pressure and blood pCO2 were not significantly modified. Lipidic patterns were not markedly improved by flunarizine treatment in comparison with values for atherosclerotic animals. These data demonstrate that flunarizine treatment counteracts the haemodynamic effects of cerebral atherosclerosis. The pronounced activity on the cerebral vessels is accompanied by a weak antilipaemic effect.