Nag S, Kilty D W
Department of Pathology, University of Toronto, Canada.
Stroke. 1997 May;28(5):1028-34. doi: 10.1161/01.str.28.5.1028.
Our recent study demonstrated that in chronic hypertension, hypertrophy of intracerebral arterioles was associated with an increase in the vascular extracellular matrix proteins: fibronectin, laminin, and collagen IV. An additional cerebral finding in chronic hypertension was hypertensive encephalopathy, in which breakdown of the blood-brain barrier (BBB) to serum proteins occurred in multifocal areas of the cortex and basal ganglia. This study was undertaken to determine which of these alterations were attenuated by antihypertensive therapy.
Two weeks after the surgery to produce chronic renal hypertension, half the hypertensive rats were treated orally with enalapril (30 mg/kg), an angiotensin-converting enzyme inhibitor, for 5 weeks. Rats were perfusion-fixed, and their brains were removed and processed for morphological studies. The effect of treatment on vascular hypertrophy was assessed by quantitative morphometry and on the vascular extracellular matrix proteins and BBB permeability alterations by immunohistochemistry.
There was increased immunoreactivity for laminin, fibronectin, and collagen IV in pial and intracerebral arterioles of untreated hypertensive rats. Immunoreactivity was greatest in arterioles in areas with breakdown of the BBB to serum proteins. Enalapril treatment for 5 weeks resulted in a significant reduction of the mean systolic blood pressure, which was accompanied by attenuation of vascular hypertrophy and attenuation of changes in the vascular extracellular matrix proteins. In addition, there was reduction in the magnitude of BBB breakdown after treatment.
Enalapril treatment had a protective effect and attenuated vascular hypertrophy and the increase in vascular extracellular matrix proteins observed in chronic hypertension. In addition, there was reduction in the magnitude of BBB breakdown.
我们最近的研究表明，在慢性高血压中，脑内小动脉肥大与血管细胞外基质蛋白（纤连蛋白、层粘连蛋白和IV型胶原）增加有关。慢性高血压的另一个脑部表现是高血压脑病，其中血脑屏障（BBB）对血清蛋白的破坏发生在皮质和基底神经节的多灶性区域。本研究旨在确定这些改变中哪些可通过抗高血压治疗得到缓解。
在制作慢性肾性高血压的手术后两周，将一半高血压大鼠口服依那普利（30mg/kg），一种血管紧张素转换酶抑制剂，持续5周。对大鼠进行灌注固定，取出大脑并进行形态学研究。通过定量形态学评估治疗对血管肥大的影响，通过免疫组织化学评估对血管细胞外基质蛋白和血脑屏障通透性改变的影响。
未治疗的高血压大鼠软脑膜和脑内小动脉中层粘连蛋白、纤连蛋白和IV型胶原的免疫反应性增加。在血脑屏障对血清蛋白破坏区域的小动脉中免疫反应性最强。依那普利治疗5周导致平均收缩压显著降低，同时伴有血管肥大减轻和血管细胞外基质蛋白变化减轻。此外，治疗后血脑屏障破坏程度降低。
依那普利治疗具有保护作用，可减轻慢性高血压中观察到的血管肥大和血管细胞外基质蛋白增加。此外，血脑屏障破坏程度降低。
