title: Effects of topical N-methyl-D-aspartate on blood-brain barrier permeability in the cerebral cortex of normotensive and hypertensive rats.
abstract: This study was performed to examine if blood-brain barrier (BBB) permeability could be increased by N-methyl-D-aspartate (NMDA) in the cerebral cortex, and to compare the degree of alteration of BBB permeability in normotensive and in chronic hypertensive rats. Twenty- to 22-week-old spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were anesthetized with isoflurane. After craniotomy in 7 animals in each group (SHR and WKY group), an NMDA patch (10 mM) was placed on one cortex (ipsilateral cortex: IC), and a normal saline patch was placed on the other cortex (control cortex: CC). The other 7 rats in each group were pretreated with MK-801 before placing NMDA and normal saline patches (SHR.MK-801 and WKY.MK-801 group). The BBB transfer coefficient (Ki) was determined using 14C-alpha-aminoisobutyric acid. The mean arterial pressures of the SHR and the SHR.MK-801 group were about 65% higher than those of the WKY and the WKY.MK-801 groups. In the WKY group, the Ki of the IC was significantly higher than that of the CC (IC: 10.0 +/- 2.7, CC: 6.2 +/- 2.4 microliters g-1 min-1). In the WKY.MK-801 group, the Ki was similar in both cortices (IC: 8.6 +/- 4.0, CC: 8.2 +/- 3.3). In the SHR group, the Ki of the IC was significantly higher than that of the CC (IC: 9.5 +/- 3.7, CC: 6.5 +/- 3.4), and the Ki of each cortex was similar to that of the corresponding cortex of the WKY group. In the SHR.MK-801 group, the Ki was similar in both cortices (IC: 7.2 +/- 1.5, CC: 7.1 +/- 2.7), and was also similar to those of the WKY.MK-801 group. Our data suggest that NMDA is involved in increasing BBB permeability. In chronic hypertension, the response of the BBB to NMDA is not altered when compared with normotension.
authors.affiliation: Department of Anesthesia, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick 08901-1977, USA.
authors.forename: O Z
authors.initials: OZ
authors.lastname: Chi
authors.forename: Q
authors.initials: Q
authors.lastname: Chang
authors.forename: H R
authors.initials: HR
authors.lastname: Weiss
mesh_terms: D000287:Administration, Topical; D000621:Aminoisobutyric Acids / Q000493:pharmacokinetics; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002199:Capillary Permeability / Q000187:drug effects*; D002540:Cerebral Cortex / Q000098:blood supply*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005740:Gases / Q000097:blood; D006973:Hypertension / Q000097:blood / Q000503:physiopathology*; D016202:N-Methylaspartate / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012016:Reference Values
chemical_list: D000621:Aminoisobutyric Acids; D005740:Gases; D016194:Receptors, N-Methyl-D-Aspartate; C100049:2-aminoisobutyric acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate