Effect of cilnidipine (FRC-8653) on autoregulation of cerebral blood flow

Effect of cilnidipine, a new calcium antagonist, on autoregulation of cerebral blood flow was studied in spontaneously hypertensive rats. Cilnidipine, at doses of 1-100 micrograms/kg, i.v., showed a hypotensive effect in a dose-dependent manner without affecting regional cerebral blood flows (rCBF) in the cerebral cortex or nucleus caudatus. At intraduodenal doses of 1 or 10 mg/kg, cilnidipine also did not affect rCBFs, while it produced long-lasting hypotension with a slow onset, decreasing blood pressure by about 40% of the pre-administration value at 10 mg/kg. Cilnidipine at a dose of 10 mg/kg, i.d. significantly lowered the lower limit for autoregulation of cerebral blood flow. These findings suggest that autoregulation of cerebral blood flow remains intact even in the excessive hypotension induced with cilnidipine and that the drug shifts the lower limits for autoregulation of cerebral blood flow downward.