Raszkiewicz J L, Linville D G, Kerwin J F, Wagenaar F, Arneric S P
Abbott Laboratories, Abbott Park, IL 60064-3500.
J Neurosci Res. 1992 Sep;33(1):129-35. doi: 10.1002/jnr.490330116.
This study sought to determine whether the activity of nitric oxide synthase (NOS) is an important physiological link required to mediate increases in cortical cerebral blood flow (CBF) elicited by electrical microstimulation of the basal forebrain (BF). Changes in cortical CBF were assessed in urethane anesthetized rats using laser-Doppler flowmetry. Microstimulation of the BF elicited stimulus-locked increases in CBF that were dependent on frequency and current intensity (up to 280% of control at 50 Hz). Infusion of the potent NOS inhibitor NG-nitro-L-arginine (L-NNA) resulted in significant dose-related reductions in the BF-elicited response at 50 Hz (3.75-60 mg/kg, i.v.), significant elevation in resting mean arterial pressure (MAP) from 106 to 160 mmHg, and modest 21% reductions in resting CBF. The stereoisomer NG-nitro-D-arginine (D-NNA) was without any effect on CBF, although at higher concentrations MAP was elevated to levels comparable to those obtained with L-NNA. Infusion of arginase was also without effect on resting or BF-elicited CBF responses. In contrast, L-arginine (100-400 mg/kg, i.v.) significantly potentiated the BF-elicited response up to an additional 38%, without affecting resting CBF or MAP. This study suggests that NO, or a related nitroso precursor formed by NOS, has a critical role in mediating regulation of cortical CBF by BF neurons.
本研究旨在确定一氧化氮合酶（NOS）的活性是否是介导由基底前脑（BF）电微刺激引起的皮质脑血流量（CBF）增加所必需的重要生理环节。在乌拉坦麻醉的大鼠中，使用激光多普勒血流仪评估皮质CBF的变化。对BF进行微刺激会引起与刺激相关的CBF增加，这取决于频率和电流强度（在50Hz时高达对照值的280%）。注入强效NOS抑制剂NG-硝基-L-精氨酸（L-NNA）导致在50Hz时BF引起的反应出现与剂量相关的显著降低（静脉注射3.75 - 60mg/kg），静息平均动脉压（MAP）从106mmHg显著升高至160mmHg，并使静息CBF适度降低21%。立体异构体NG-硝基-D-精氨酸（D-NNA）对CBF没有任何影响，尽管在较高浓度时MAP升高到与L-NNA相当的水平。注入精氨酸酶对静息或BF引起的CBF反应也没有影响。相比之下，L-精氨酸（静脉注射100 - 400mg/kg）可使BF引起的反应显著增强，额外增加高达38%，而不影响静息CBF或MAP。本研究表明，NO或由NOS形成的相关亚硝基前体在介导BF神经元对皮质CBF的调节中起关键作用。
