Effects of isoproterenol on blood-brain barrier permeability in rats

This study was performed to examine whether the direct topical application of isoproterenol to the cerebral cortex could modify the blood-brain barrier (BBB) permeability and whether this effect could be blocked 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 was placed on one cortex (Ipsilateral Cortex: IC) and a normal saline patch was placed on the other cortex (Control Cortex: CC). Another 6 animals were pretreated with Timolol 1.5 mg kg(-1) i.v. before the placement of high dose isoproterenol patches. The BBB transfer coefficient (Ki) was determined using C-14-alpha-aminoisobutyric acid. Mean arterial blood pressure decreased after low-and high-dose isoproterenol patches. 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 that of the corresponding CC. Pretreatment with Timolol prevented the increase 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 parenchyma increased the permeability of the BBB, and that this effect could be prevented with a beta-adrenoceptor antagonist.