White R P, Vallance P, Markus H S
Clinical Neurosciences, Guy's, King's and St Thomas' School of Medicine and Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK.
Clin Sci (Lond). 2000 Dec;99(6):555-60.
Cerebral blood flow is maintained constant over a range of cerebral perfusion pressures by cerebral autoregulation. Impaired cerebral autoregulation may be important in the pathogenesis of cerebral ischaemia. The mechanisms mediating normal cerebral autoregulation in humans are poorly understood. We used a recently described transcranial Doppler technique, which allows non-invasive measurement of dynamic cerebral autoregulation, to test the hypothesis that nitric oxide mediates cerebral autoregulation. The rate of rise of middle cerebral artery blood flow velocity, compared with that of arterial blood pressure, was determined following a stepwise fall in arterial blood pressure, in order to calculate an autoregulatory index. The effect of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) on dynamic autoregulation was compared with that of noradrenaline titrated to result in a similar rise in blood pressure. Six healthy subjects were studied in each group. The mean (S.D.) change in autoregulatory index following noradrenaline at a similar pressor dose was significantly greater than the change following the L-NMMA bolus: 1. 1 (1.2) compared with -0.8 (0.8) for the left middle cerebral artery (P=0.002), and 1.1 (0.8) compared with -0.8 (0.8) for the right middle cerebral artery (P=0.002). There was no difference in the mean (S.D.) blood pressure increase resulting from the two agents: L-NMMA, 19.7 (7.4) mmHg; noradrenaline, 15.5 (4.8) mmHg (P=0.281). These results suggest that nitric oxide mediates at least part of the dynamic phase of cerebral autoregulation in humans. Reduced nitric oxide release may play a role in the impaired cerebral autoregulation seen in patients with, or at risk of, cerebral ischaemia.
通过脑自动调节，脑血流量在一定范围的脑灌注压下保持恒定。脑自动调节受损可能在脑缺血的发病机制中起重要作用。人们对介导人类正常脑自动调节的机制了解甚少。我们使用了一种最近描述的经颅多普勒技术，该技术可对动态脑自动调节进行无创测量，以检验一氧化氮介导脑自动调节的假说。在动脉血压逐步下降后，测定大脑中动脉血流速度与动脉血压的上升速率，以计算自动调节指数。将一氧化氮合酶抑制剂N（G）-单甲基-L-精氨酸（L-NMMA）对动态自动调节的作用与滴定至导致血压类似升高的去甲肾上腺素的作用进行比较。每组研究6名健康受试者。在相似的升压剂量下，去甲肾上腺素后自动调节指数的平均（标准差）变化显著大于L-NMMA推注后的变化：左大脑中动脉为1.1（1.2），而L-NMMA推注后为-0.8（0.8）（P = 0.002）；右大脑中动脉为1.1（0.8），而L-NMMA推注后为-0.8（0.8）（P = 0.002）。两种药物引起的平均（标准差）血压升高无差异：L-NMMA为19.7（7.4）mmHg；去甲肾上腺素为15.5（4.8）mmHg（P = 0.281）。这些结果表明，一氧化氮介导了人类脑自动调节的至少部分动态阶段。一氧化氮释放减少可能在脑缺血患者或有脑缺血风险的患者中出现的脑自动调节受损中起作用。
