Watanabe K, Dozen M, Hayashi Y
Pharmaceuticals Research Laboratories, Fujirebio Inc., Tokyo, Japan.
Nihon Yakurigaku Zasshi. 1995 Dec;106(6):393-9. doi: 10.1254/fpj.106.393.
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.
在自发性高血压大鼠中研究了新型钙拮抗剂西尼地平对脑血流自动调节的影响。静脉注射剂量为1 - 100微克/千克的西尼地平呈剂量依赖性降压作用,且不影响大脑皮层或尾状核的局部脑血流(rCBF)。十二指肠内给予1或10毫克/千克剂量的西尼地平也不影响rCBF,但会产生起效缓慢的持久降压作用,10毫克/千克剂量时血压降低约为给药前值的40%。十二指肠内给予10毫克/千克剂量的西尼地平显著降低了脑血流自动调节的下限。这些发现表明,即使在西尼地平诱导的过度低血压状态下,脑血流自动调节仍保持完整,且该药物使脑血流自动调节的下限向下移动。