Borges N, Sarmento A, Azevedo I
Institute of Pharmacology and Therapeutics, Medical Faculty, Porto, Portugal.
J Auton Pharmacol. 1999 Aug;19(4):209-17. doi: 10.1046/j.1365-2680.1999.00137.x.
The effects of adrenergic drugs on the formation and resolution of cerebral oedema in a rat model of cold-induced vasogenic brain oedema were studied. Evans blue dye extravasation, water content and ultrastructural alterations (pinocytotic vesicle formation in capillary endothelial cells and apparent water accumulation in the brain parenchyma) were evaluated in parietal cortex. Previous administration of the alpha-adrenoceptor antagonist phenoxybenzamine produced a reduction of Evans blue extravasation and water content, diminished vesicle formation and reduced water accumulation. Previous administration of the beta2-adrenoceptor agonist clenbuterol reduced Evans blue extravasation and water content, but did not change vesicle frequency. The effects of clenbuterol on Evans blue passage to the brain were blocked by timolol (beta-adrenoceptor antagonist) but not by metoprolol (selective beta1-adrenoceptor antagonist). When given after the application of cold, clenbuterol was also able to reduce Evans blue and water content in the brain. Isoprenaline (beta-adrenoceptor agonist that does not cross the blood-brain barrier) showed a reduction in Evans blue extravasation only when given intracerebroventricularly. Vinblastine (a drug that prevents vesicle formation) produced a reduction of the amount of pinocytotic vesicles. We conclude that there is an influence of the central adrenergic nervous system on the formation and/or resolution of vasogenic brain oedema and that the alterations on water movement and Evans blue transport mediated by adrenergic drugs seem to be due, at least in part, to alterations of pinocytotic activity in capillary endothelial cells.
研究了肾上腺素能药物对冷诱导血管源性脑水肿大鼠模型中脑水肿形成和消退的影响。评估了顶叶皮质中的伊文思蓝染料外渗、含水量和超微结构改变（毛细血管内皮细胞中吞饮小泡形成以及脑实质中明显的积水）。预先给予α-肾上腺素能受体拮抗剂酚苄明可减少伊文思蓝外渗和含水量，减少小泡形成并减少积水。预先给予β2-肾上腺素能受体激动剂克仑特罗可减少伊文思蓝外渗和含水量，但不改变小泡频率。克仑特罗对伊文思蓝进入脑内的作用被噻吗洛尔（β-肾上腺素能受体拮抗剂）阻断，但未被美托洛尔（选择性β1-肾上腺素能受体拮抗剂）阻断。在施加寒冷后给予克仑特罗，也能够减少脑中的伊文思蓝和含水量。异丙肾上腺素（一种不能穿过血脑屏障的β-肾上腺素能受体激动剂）仅在脑室内给药时才显示伊文思蓝外渗减少。长春碱（一种阻止小泡形成的药物）使吞饮小泡数量减少。我们得出结论，中枢肾上腺素能神经系统对血管源性脑水肿的形成和/或消退有影响，并且肾上腺素能药物介导的水移动和伊文思蓝转运的改变似乎至少部分归因于毛细血管内皮细胞中吞饮活性的改变。
