Prado R, Watson B D, Kuluz J, Dietrich W D
Cerebral Vascular Disease Research Center, University of Miami School of Medicine, FL 33101.
Stroke. 1992 Aug;23(8):1118-23; discussion 1124. doi: 10.1161/01.str.23.8.1118.
We determined the effects of inhibiting the production of cerebral endothelium-derived nitric oxide on pial artery diameter, cortical blood flow, and vascular morphology.
An inhibitor of endothelium-derived nitric oxide synthesis, NG-nitro-L-arginine methyl ester hydrochloride (L-NAME), or an equivalent volume of 0.9% saline was infused into rats intra-arterially in a retrograde fashion via the right external carotid artery at a rate of 3 mg/kg/min to a total dose of 190 mg/kg or intravenously at 1 mg/kg/min to a total dose of 15 mg/kg. Large pial arteries were continuously visualized through an operating microscope, and cortical cerebral blood flow was monitored by laser-Doppler flowmetry. To localize areas of morphological interest, the protein tracer horseradish peroxidase was injected 15 minutes before termination of the L-NAME infusion and the rats were perfusion-fixed 15 minutes later for light and electron microscopic analysis.
Infusion of L-NAME significantly raised arterial blood pressure at both doses (for 190 mg/kg, from 103.2 +/- 3.4 to 135 +/- 3.4 mm Hg; for 15 mg/kg, from 125 +/- 2.8 to 144.4 +/- 4.0 mm Hg). Pial arteries constricted within 10 minutes after the start of the intracarotid infusion to 40% of the preinfusion diameter, while cortical cerebral blood flow decreased to an average of 72.5% of that at baseline. Morphological abnormalities in the experimental rats included microvascular stasis and focal areas of blood-brain barrier disruption to protein. Ultrastructural examination of cortical leaky sites revealed constricted arterioles with many endothelial pinocytotic vesicles and microvilli.
These observations suggest that inhibition of endothelium-derived nitric oxide synthesis affects the relation between cerebral arterial diameter and cerebral blood flow and can lead to subtle cerebral vascular pathological changes consistent with focal brain ischemia.
我们确定了抑制脑内皮源性一氧化氮生成对软脑膜动脉直径、皮质血流及血管形态的影响。
通过右颈外动脉以逆行方式经动脉内以3mg/kg/min的速率向大鼠输注内皮源性一氧化氮合成抑制剂盐酸N-硝基-L-精氨酸甲酯（L-NAME）或等体积的0.9%盐水，总剂量为190mg/kg，或以1mg/kg/min的速率静脉输注，总剂量为15mg/kg。通过手术显微镜持续观察大的软脑膜动脉，并用激光多普勒血流仪监测皮质脑血流。为了定位感兴趣的形态学区域，在L-NAME输注终止前15分钟注射蛋白示踪剂辣根过氧化物酶，15分钟后对大鼠进行灌注固定以进行光镜和电镜分析。
两种剂量的L-NAME输注均显著升高动脉血压（190mg/kg时，从103.2±3.4mmHg升至135±3.4mmHg；15mg/kg时，从125±2.8mmHg升至144.4±4.0mmHg）。颈内动脉输注开始后10分钟内软脑膜动脉收缩至输注前直径的40%，而皮质脑血流降至基线时平均值的72.5%。实验大鼠的形态学异常包括微血管淤滞和血脑屏障对蛋白的局灶性破坏区域。对皮质渗漏部位的超微结构检查显示小动脉收缩，伴有许多内皮吞饮小泡和微绒毛。
这些观察结果表明，抑制内皮源性一氧化氮合成会影响脑动脉直径与脑血流之间的关系，并可导致与局灶性脑缺血一致的细微脑血管病理变化。
