Examination of potential mechanisms in the enhancement of cerebral blood flow by hypoglycemia and pharmacological doses of deoxyglucose
Examination of potential mechanisms in the enhancement of cerebral blood flow by hypoglycemia and pharmacological doses of deoxyglucose
复制标题
DOI：
10.1097/00004647-199701000-00008
复制
发表时间：
1997-01-01
影响因子：
6.3
通讯作者：
Sokoloff, L
中科院分区：
文献类型：
--
作者：
Horinaka, N;Artz, N;Sokoloff, L
当低血糖限制大脑的葡萄糖供应或药物剂量的2-脱氧葡萄糖(DG)抑制葡萄糖代谢时，脑血流量(CBF)增加。本文对胰岛素诱导低血糖的非麻醉大鼠的研究表明，在动脉血糖降至2.5~3.0 mM之前，用[C-14]安替比林法测得的脑血流量增加相对较小，此时脑血流量急剧上升。排除了胰岛素对脑血流量的直接影响；在葡萄糖注射维持的正常血糖条件下给予胰岛素对脑血流量没有影响。胰岛素治疗提高了血浆乳酸水平，降低了血浆K+和HCO3-浓度及动脉pH值。然而，这不可能与脑血流量增加有关，因为正常血糖条件下的胰岛素有类似的作用，而不影响脑血流量；此外，药物剂量(静脉注射200 mg/kg)抑制脑葡萄糖代谢增加脑血流量，就像胰岛素低血糖一样，而不改变血浆乳酸和K+水平以及动脉血气压力和pH。一氧化氮似乎也不是CBF增加的中介因素。慢性阻断一氧化氮合酶的活性，每日两次，注射NG-硝基-L-精氨酸甲酯4天或急性单次静脉注射。注射使正常血糖、低血糖和DG治疗的大鼠的动脉血压升高，脑血流量降低，但不能显著降低由于胰岛素诱导的低血糖(动脉血糖水平，2.5-3 mM)或药物剂量的脱氧葡萄糖引起的脑血流量的增加。
Cerebral blood flow (CBF) rises when the glucose supply to the brain is limited by hypoglycemia or glucose metabolism is inhibited by pharmacological doses of 2-deoxyglucose (DG). The present studies in unanesthetized rats with insulin-induced hypoglycemia show that the increases in CBF, measured with the [C-14]iodoantipyrine method, are relatively small until arterial plasma glucose levels fall to 2.5 to 3.0 mM, at which point CBF rises sharply. A direct effect of insulin on CBF was excluded; insulin administered under euglycemic conditions maintained by glucose injections had no effects on CBF. Insulin administration raised plasma lactate levels and decreased plasma K+ and HCO3- concentrations and arterial pH. These could not, however, be related to the increased CBF because insulin under euglycemic conditions had similar effects without affecting CBF; furthermore, the inhibition of brain glucose metabolism with pharmacological doses (200 mg/kg intravenously) of DG increased CBF, just like insulin hypoglycemia, without altering plasma lactate and K+ levels and arterial blood gas tensions and pH. Nitric oxide also does not appear to mediate the increases in CBF. Chronic blockade of nitric oxide synthase activity by twice daily i.p, injections of NG-nitro-L-arginine methyl ester for 4 days or acutely by a single i.v. injection raised arterial blood pressure and lowered CBF in normoglycemic, hypoglycemic, and DG-treated rats but did not significantly reduce the increases in CBF due to insulin-induced hypoglycemia (arterial plasma glucose levels, 2.5-3 mM) or pharmacological doses of deoxyglucose.