Fassot C, Lambert G, Gaudet-Lambert E, Friberg P, Elghozi J L
Laboratoire de Pharmacologie, CNRS UMR 8604, Faculté de Médecine Necker, Paris, France.
Brain Res Bull. 1999 Sep 15;50(2):127-32. doi: 10.1016/s0361-9230(99)00089-1.
Subarachnoid haemorrhage is a serious condition often accompanied by delayed cerebral ischaemia. Earlier reports have provided evidence suggesting a role for angiotensin II in the development of cerebral vasospasm following subarachnoid bleeding. We sought to examine the influence of angiotensin II blockade with losartan on blood pressure and survival in animals following experimental subarachnoid haemorrhage, induced in conscious rats by injecting homologous blood via a catheter placed along the surface of the brain. We combined measurements of plasma renin activity with blood pressure recording in order to examine renin-angiotensin system activation following experimental subarachnoid haemorrhage. Following subarachnoid injury an approximately three-fold increase in plasma renin activity occurred (3.4 +/- 1.0 vs. 10.1 +/- 1.8 ng angiotensin I produced/ml/h, p < 0.01). In animals treated with losartan (20 mg/kg) prior to the induction of subarachnoid haemorrhage blood pressure fell dramatically following the cerebral injury (124 +/- 5 vs. 94 +/- 7 mmHg, p < 0.001), whereas blood pressure remained unchanged in control animals. Survival was markedly reduced in those animals treated with losartan. Given the pronounced decrease in blood pressure and impaired survival following subarachnoid haemorrhage in animals treated with losartan, it would appear that the acute activation of the renin-angiotensin system following this insult is in fact a desirable, compensatory response.
蛛网膜下腔出血是一种严重疾病,常伴有迟发性脑缺血。早期报告提供的证据表明,血管紧张素II在蛛网膜下腔出血后脑血管痉挛的发生中起作用。我们试图研究用氯沙坦阻断血管紧张素II对实验性蛛网膜下腔出血后动物血压和存活率的影响,实验性蛛网膜下腔出血是通过沿脑表面放置的导管向清醒大鼠注射同源血液诱导产生的。我们将血浆肾素活性测量与血压记录相结合,以研究实验性蛛网膜下腔出血后肾素-血管紧张素系统的激活情况。蛛网膜下腔损伤后,血浆肾素活性出现约三倍的增加(每毫升每小时产生的血管紧张素I:3.4±1.0对10.1±1.8纳克,p<0.01)。在诱导蛛网膜下腔出血前用氯沙坦(20毫克/千克)治疗的动物中,脑损伤后血压急剧下降(124±5对94±7毫米汞柱,p<0.001),而对照动物的血压保持不变。用氯沙坦治疗的动物存活率明显降低。鉴于用氯沙坦治疗的动物在蛛网膜下腔出血后血压显著下降且存活率受损,看来这种损伤后肾素-血管紧张素系统的急性激活实际上是一种有益的代偿反应。