Effects of isoproterenol on blood-brain barrier permeability in rats

Abstract

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 Timololl a β-adrenergic receptor antagonist without a membrane stabilizing effect. After a craniotomy in each animall 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 14C-α-aminoisobutyric acid. Mean arterial blood pressure decreased after low- and high-dose isoproterenol patches. The low- and highdose of isoproterenol increased Ki by 58% (IC: 5.94 ± 2.021 CC: 3.77± 1.75 µlg min-1) and 66% (IC: 6.97± 3.661 CC: 4.19± 2.48 µlg 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 µlg min-1). Our data demonstrate that a direct application of a β-adrenergic receptor agonist to the brain parenchyma increased the permeability of the BBBI and that this effect could be prevented with a β-adrenoceptor antagonist. [Neural Res 1998; 20: 259-264]