CEREBRAL ISCHEMIA--ENDOTHELIN-1 AND NITRIC OXIDE

我们已经探讨了生产不平衡的可能性 内皮素-1和一氧化氮可能加重脑损伤 受伤。已知的一种有效的血管收缩多肽ET-1和NO，AN 内皮松弛因子是在其他血管活性物质中产生的 血管内皮细胞和大脑其他细胞中的介体。 有人提出，ET-1的产生之间的不平衡 内皮细胞中的NO可能在脑血管疾病中起一定作用。 特别是，观察到的血浆和/或血浆中ET-1水平的升高 脑卒中、高血压和高血压患者的脑脊液 血管痉挛与ET-1在脑血管疾病发病机制中的关系 进程。这项研究的目的是确定大脑 脑缺血导致脑脊液ET-1升高，这可能是 通过抑制一氧化氮合酶(NOS)而改变。双侧颈动脉 沙土鼠闭塞(15分钟)或释放(5-120分钟) 作为脑缺血的模型。治疗包括以下两种 硝基-L精氨酸甲酯或D-硝基-L精氨酸甲酯40 Mg/kg B.W.)在林格氏溶液(0.5ml)或单独给出的溶剂中 缺血诱导前4小时腹腔注射。类似 以处理过的假手术动物作为对照。全身血 血压(SBP)、脑血流量(CBF)、颞叶和直肠 在麻醉状态下连续监测温度(氟烷1.5% 和NO2/O2 1%)和自发通风沙土鼠。获取脑脊液 在每个实验期结束时从枕大池取出。关卡 用放射免疫法测定脑脊液中ET-1的含量。温度不是 明显受到任何一种治疗的影响。SBP仅在NLA升高- 缺血前和缺血后的处理动物(NLA 77.67加-1.88 和85.33正负1.75毫米汞柱；其他66.67正负 分别为3.45和72.5加负2.17毫米汞)，尽管存在缺血 各组沙土鼠的SBP均有类似的升高。脑血流量减少 (对照组的0.5%)。NLA治疗，但不是 D-NAME阻止再灌注期CBF的初步完全恢复 (7.5分钟)。在脑脊液中，ET-1水平比对照组高2-3倍 缺血15min后早期再灌流。接受NLA治疗的动物 已显示脑缺血后脑脊液中ET-1含量升高 单独进行再灌流。这是第一次展示ET的变化- 1脑缺血再灌注期脑脊液含量。抑制一氧化氮合酶会产生一种 除SBP外，脑脊液中ET-1的早期和持续升高 脑缺血/再灌流时脑血流量升高及不完全恢复。

We have explored the possibility of imbalance between the production of endothelin-1 (ET-1) and nitric oxide (NO) which may exacerbate brain injury. ET-1 a known potent vasoconstrictor peptide and NO, an endothelial relaxing factor, are produced among other vasoactive mediators in the vascular endothelium and in other cells in the brain. It has been suggested that an imbalance between the production of ET-1 and NO in the endothelium may play a role in cerebrovascular disorders. In particular, the observed increased ET-1 levels in plasma and/or cerebrospinal fluid (CSF) of patients with stroke, hypertension and vasospasm implicate ET-1 in the pathogenesis of cerebrovascular disease process. The aim of this study was to establish whether cerebral ischemia leads to CSF elevation of ET-1 which could be additionally altered by inhibition of NO synthase (NOS). Bilateral carotid artery occlusion (15 min) alone or with release (5-120 min) in gerbils served as a model for cerebral ischemia. The treatment consisted of either nitro-L-arginine (NLA) or D-nitro-L-arginine methyl ester (D-NAME) 40 mg/kg b.w.) in Ringer's solution (0.5ml) or the solvent alone given intraperitoneally 4 hr prior to the induction of ischemia. Similarly treated sham-operated animals were used as controls. Systemic blood pressure (SBP), cerebral blood flow (CBF), temporal and rectal temperature were continuously monitored in anesthetized (halothane 1.5% and NO2/O2 1%) and spontaneously ventilated gerbils. CSF was obtained from the cisterna magna at the end of each experimental period. The level of ET-1 in CSF was measured by radioimmunoassay. Temperature was not significantly affected by either treatment. SBP was only elevated in NLA- treated animals during pre- and postischemia (NLA 77.67 plus minus 1.88 and 85.33 plus minus1.75 mm Hg, respectively; others 66.67 plus minus 3.45 and 72.5 plus minus 2.17 mm Hg, respectively), although ischemia induced a similar rise in SBP in all groups of gerbils. CBF was reduced (0.5% of control) during ischemia in all groups. NLA treatment but not D-NAME prevented the initial complete recovery of CBF during reperfusion (7.5 min). In the CSF, the ET-1 level was raised 2-3 fold over controls in early reperfusion after 15 min of ischemia. The NLA-treated animals already showed the increased content of ET-1 in the CSF after ischemia alone with reperfusion. This is the first demonstration of changes in ET- 1 content of CSF in ischemia/reperfusion. NOS inhibition produces an early and persistent rise in ET-1 levels of CSF in addition to SBP elevation and incomplete recovery of CBF during ischemia/reperfusion.