Effects of lipopolysaccharide on the blood-brain barrier permeability in prolonged nitric oxide blockade-induced hypertensive rats

Abstract

The authors investigated the effects of lipopolysaccharide (LPS) on the blood-brain harrier (BBB) integrity and the activity of astrocytes during the N-(psi)-nitro-L-arginine methyl ester (L-NAME) hypertension followed by angiotensin (ANG) II in rats. They measured the changes in the BBB permeability using the Evans blue (EB) dye and concomitantly in the levels of TNF-alpha, IL-1ss and IL-6 in serum and nitric oxide in plasma. The authors performed two tight junction-specific proteins, zondula occludens-I and occludin, and filial fibrillary acidic protein, by using inummohisto-chemical method. The serum levels of TNF-alpha. IL- 1ss, IL-6, and the plasma level of nitric oxide significantly increased in LPS-treated rats (p <. 01). The EB dye extravasation increased in cerebellum (p < .001) and diencephalon (p < .05),)of L-NAME plus ANG II-treated animals. However, LPS reduced the increased EB dye estravasation in the brain regions of L-NAME-induced hypertensive rats treated with ANG II (p <.001). In L-NAME, there was a considerable loss of staining in both zonula occludens-1 and occludin. Staining for zonula occludens-I and occludin was highly intensive in animals treated with LPS. Glial fibrillary acidic protein staining teas seen in a few astrocytes in brains of L-NAME-treated animals. However, this staining showed an increased intensity in the brain sections of animals treated with LPS. This study, indicates that. ill L-NAME hypertensive rats. ANG II leads to an increase in the ectravasation of EB dye to brain as a result of decreased activity of tight junction proteins and astrocytes, and LPS could significantly attenuate the EB dye transport to the brain through the increased activity of tight junction proteins and astrocytes.