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 14C-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 microl g min(-1)) and 66% (IC: 6.97+/-3.66, CC: 4.19+/-2.48 microl 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 microl 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.
Chi
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OZ
Department of Anesthesia, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick 08901-1977, USA.
Wang
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Chang
Q
Q
Weiss
H R
HR
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000621:Aminoisobutyric Acids / Q000493:pharmacokinetics*; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002250:Carbon Radioisotopes; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013999:Timolol / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D000621:Aminoisobutyric Acids; D002250:Carbon Radioisotopes; C100049:2-aminoisobutyric acid; D013999:Timolol; D007545:Isoproterenol