EFFECTS OF ISOPROTERENOL ON BLOOD-BRAIN-BARRIER PERMEABILITY IN RATS

This study was performed to examine whether the direct topical applica tion of isoproterenol to the cerebral cortex could modify the blood-br ain barrier (BBB) permeability and whether this effect could be blocke d by Timolol, a beta-adrenergic receptor antagonist without a membrane stabilizing effect. After a craniotomy in each animal, a low-dose (10 (-4) M, n = 6) or a high-dose (10(-3) M, n = 6) isoproterenol patch wa s placed on one cortex (Ipsilateral Cortex: IC) and a normal saline pa tch was placed on the other cortex (Control Cortex: CC). Another 6 ani mals were pretreated with Timolol 1.5 mg kg(-1) i.v. before the placem ent of high dose isoproterenol patches. The BBB transfer coefficient ( Ki) was determined using C-14-alpha-aminoisobutyric acid. Mean arteria l blood pressure decreased after low-and high-dose isoproterenol patch es. The low-and high dose of isoproterenol increased Ki by 58% (IC: 5. 94 +/- 2.02, CC: 3.77 +/- 1.75 mu l g min(-1)) and 66% (IC: 6.97 +/- 3 .66, CC: 4.19 +/- 2.48 mu l g min(-1)) respectively when compared to t hat of the corresponding CC. Pretreatment with Timolol prevented the i ncrease of the Ki by a high-dose of isoproterenol (IC: 5.33 +/- 1.88, CC: 5.66 +/- 1.72 mu l g min(-1)). Our data demonstrate that a direct application of a beta-adrenergic receptor agonist to the brain parench yma increased the permeability of the BBB, and that this effect could be prevented with a beta-adrenoceptor antagonist.