White R P, Deane C, Vallance P, Markus H S
Department of Clinical Neurosciences, King's College School of Medicine and Dentistry and the Institute of Psychiatry, London, UK.
Stroke. 1998 Feb;29(2):467-72. doi: 10.1161/01.str.29.2.467.
Animal studies suggest that nitric oxide (NO) is important in basal cerebral blood flow (CBF) regulation and that it may mediate the vasodilatory response to carbon dioxide. We investigated its role in the human circulation using the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA).
L-NMMA was administered as an intravenous bolus at three doses (1, 3, and 10 mg/kg). CBF was assessed by color velocity ultrasonic imaging of internal and common carotid artery volume flow (ICA flow and CCA flow) and transcranial Doppler ultrasound measurement of middle cerebral artery flow velocity (MCAv). The pressor effect of L-NMMA was controlled for by comparison with noradrenaline titrated to effect an equivalent blood pressure elevation.
L-NMMA produced a dose-dependent reduction in basal mean+/-SD CCA flow from 415.2+/-51.9 to 294+/-56.2 mL/min (at 10 mg/kg) and ICA flow from 268.8+/-59.4 to 226.2+/-72.6 mL/min (P<.005 and P<.05, respectively, comparing areas under the dose-response curve). This was reversed by L-arginine. Mean+/-SD systemic blood pressure rose from 85.2+/-6.4 to 100.8+/-9.6 mm Hg (P<.01). There was no significant reduction in MCAv. There was no significant change in the CBF response to either 6% or 8% carbon dioxide after L-NMMA. Noradrenaline produced a lesser fall in basal CCA flow (12.0%) but had a similar effect on the hypercapnic response.
Basal NO release is important in controlling human CBF, but intravenously administered L-NMMA does not inhibit the hypercapnic hyperemic response in humans. The discrepancy between CBF and MCAv after L-NMMA administration is consistent with MCA vasoconstriction. Neuronal NO synthase inhibition may be protective in stroke. However, our results suggest that nonselective NO synthase inhibitors such as L-NMMA should be used with caution because they reduce CBF.
动物研究表明，一氧化氮（NO）在基础脑血流量（CBF）调节中起重要作用，且可能介导对二氧化碳的血管舒张反应。我们使用一氧化氮合酶抑制剂N(G)-单甲基-L-精氨酸（L-NMMA）研究其在人体循环中的作用。
L-NMMA以三种剂量（1、3和10mg/kg）静脉推注给药。通过彩色速度超声成像评估颈内动脉和颈总动脉容积流量（ICA流量和CCA流量）以及经颅多普勒超声测量大脑中动脉血流速度（MCAv）来评估CBF。通过与滴定至产生等效血压升高的去甲肾上腺素比较来控制L-NMMA的升压作用。
L-NMMA使基础平均±标准差CCA流量从415.2±51.9降至294±56.2mL/min（10mg/kg时），ICA流量从268.8±59.4降至226.2±72.6mL/min（分别比较剂量反应曲线下面积，P<0.005和P<0.05）。这被L-精氨酸逆转。平均±标准差全身血压从85.2±6.4升至100.8±9.6mmHg（P<0.01）。MCAv无显著降低。L-NMMA后对6%或8%二氧化碳的CBF反应无显著变化。去甲肾上腺素使基础CCA流量下降较少（12.0%），但对高碳酸血症反应有类似作用。
基础NO释放对控制人体CBF很重要，但静脉注射L-NMMA不抑制人体的高碳酸血症性充血反应。L-NMMA给药后CBF和MCAv之间的差异与MCA血管收缩一致。神经元型NO合酶抑制在中风中可能具有保护作用。然而，我们的结果表明，应谨慎使用L-NMMA等非选择性NO合酶抑制剂，因为它们会降低CBF。
