Edwards D H, Byrne J V, Griffith T M
Department of Radiology, University of Wales College of Medicine, Cardiff.
J Neurosurg. 1992 May;76(5):830-7. doi: 10.3171/jns.1992.76.5.0830.
The authors have investigated the hypothesis that loss of endothelium-derived relaxing factor (EDRF) activity contributes to cerebral vasospasm after subarachnoid hemorrhage. Adventitial exposure to hemoglobin was studied angiographically by injecting purified hemoglobin solution or autologous whole blood into the cisterna magna of anesthetized pigs. Both interventions induced intra- but not extracerebral vasoconstriction, which persisted for 2 and 7 days, respectively. Cyclic guanosine monophosphate (cGMP) levels were measured in isolated buffer-perfused pig intrathecal arteries to quantify inhibition of basal EDRF activity by hemoglobin. Adventitial exposure was less effective than intimal exposure, 10 microM hemoglobin applied adventitially for 30 minutes having an effect equivalent to that of 1 microM applied intraluminally for 5 minutes. The depression of cGMP levels by hemoglobin was reversible and equivalent to the effect of endothelial denudation or incubation with NG-nitro-L-arginine methyl ester, so that the effects of hemoglobin can be attributed to a specific action on EDRF rather than interaction with a nitric oxide-like substance produced by vascular smooth muscle or adventitial nerves. Cyclic GMP levels in isolated arteries were unchanged after in vivo exposure to hemoglobin for either 2 or 7 days or to whole blood for 2 days, and were reduced by intraluminal perfusion with 1 microM hemoglobin. In contrast, after 7 days of in vivo exposure to whole blood, cGMP levels were already depressed, and not further reduced by intraluminal perfusion with 1 microM hemoglobin. The findings support the view that adventitially applied hemoglobin can inhibit basal EDRF activity and that in vivo adventitial exposure to whole blood leads to a reduction in basal cGMP levels in association with vasoconstriction of intrathecal arteries. Both mechanisms could contribute to the clinical syndrome of cerebral vasospasm after subarachnoid hemorrhage.
内皮源性舒张因子（EDRF）活性丧失导致蛛网膜下腔出血后脑血管痉挛。通过将纯化的血红蛋白溶液或自体全血注入麻醉猪的大池，以血管造影术研究外膜暴露于血红蛋白的情况。两种干预均诱导了脑内而非脑外血管收缩，分别持续2天和7天。在分离的缓冲液灌注猪鞘内动脉中测量环磷酸鸟苷（cGMP）水平，以量化血红蛋白对基础EDRF活性的抑制作用。外膜暴露不如内膜暴露有效，外膜应用10 microM血红蛋白30分钟的效果相当于腔内应用1 microM血红蛋白5分钟的效果。血红蛋白对cGMP水平的降低是可逆的，且等同于内皮剥脱或与NG-硝基-L-精氨酸甲酯孵育的效果，因此血红蛋白的作用可归因于对EDRF的特异性作用，而非与血管平滑肌或外膜神经产生的一氧化氮样物质相互作用。在体内暴露于血红蛋白2天或7天或全血2天后，分离动脉中的cGMP水平未发生变化，而腔内灌注1 microM血红蛋白可使其降低。相反，在体内暴露于全血7天后，cGMP水平已降低，腔内灌注1 microM血红蛋白不会使其进一步降低。这些发现支持以下观点：外膜应用血红蛋白可抑制基础EDRF活性，且体内外膜暴露于全血会导致鞘内动脉血管收缩，同时基础cGMP水平降低。这两种机制都可能导致蛛网膜下腔出血后脑血管痉挛的临床综合征。
