Effects of topical N-methyl-D-aspartate on blood-brain barrier permeability in the cerebral cortex of normotensive and hypertensive rats.
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.
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Department of Anesthesia, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick 08901-1977, USA.
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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
D000621:Aminoisobutyric Acids; D005740:Gases; D016194:Receptors, N-Methyl-D-Aspartate; C100049:2-aminoisobutyric acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate