Vraamark T, Waldemar G, Edvinsson L, Paulson O B
Department of Neurology, Rigshospitalet, Copenhagen, Denmark.
Pharmacol Toxicol. 1997 Jan;80(1):38-43. doi: 10.1111/j.1600-0773.1997.tb00281.x.
The effect of neuropeptide Y inhibition with alpha-trinositol on the cerebral blood flow autoregulation was studied in Wistar Kyoto rats. alpha-Trinositol was tested in two doses: one dose (5 mg kg-1 hr-1) selectively affecting neuropeptide Y and one higher dose (50 mg kg-1 hr-1) affecting both neuropeptide Y and the adrenergic response. The cerebral blood flow was measured with the intracarotid 133xenon injection method in halothane nitrous oxide-anaesthetized animals. Blood pressure was raised by norepinephrine infusion and lowered by controlled haemorrhage in separate groups of rats. In addition we examined the effect of alpha-trinositol on neuropeptide Y-induced contraction of cerebral vessels in vitro. The in vitro study demonstrated inhibition of neuropeptide Y-induced contraction with a alpha-trinositol dose selective of neuropeptide Y. The in vivo study demonstrated that cerebral blood flow autoregulation was preserved after both doses of alpha-trinositol. alpha-Trinositol in the low neuropeptide Y-selective dose (5 mg kg-1 hr-1) did not affect the blood pressure limits of cerebral blood flow autoregulation, but the higher dose (50 mg kg-1 hr-1) of alpha-trinositol shifted the upper blood pressure limit of cerebral blood flow autoregulation towards lower blood pressures, an effect probably due to inhibition of both the adrenergic and neuropeptide Y systems.
在Wistar Kyoto大鼠中研究了用α-三肌醇抑制神经肽Y对脑血流自动调节的影响。对α-三肌醇进行了两种剂量的测试:一种剂量(5毫克/千克/小时)选择性地影响神经肽Y,另一种较高剂量(50毫克/千克/小时)同时影响神经肽Y和肾上腺素能反应。在氟烷一氧化二氮麻醉的动物中,采用颈内动脉注射133氙的方法测量脑血流量。在不同组的大鼠中,通过输注去甲肾上腺素升高血压,通过控制性出血降低血压。此外,我们还研究了α-三肌醇对体外神经肽Y诱导的脑血管收缩的影响。体外研究表明,α-三肌醇对神经肽Y诱导的收缩具有剂量选择性抑制作用。体内研究表明,两种剂量的α-三肌醇后,脑血流自动调节均得以保留。低剂量(5毫克/千克/小时)的α-三肌醇对脑血流自动调节的血压极限没有影响,但高剂量(50毫克/千克/小时)的α-三肌醇使脑血流自动调节的血压上限向较低血压方向移动,这一效应可能是由于肾上腺素能和神经肽Y系统均受到抑制。