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Effects of atorvastatin on blood-brain barrier permeability during L-NAME hypertension followed by angiotensin-II in rats.

Abstract：

:Recent studies suggest that 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, statins, can have direct effects on blood vessels beyond their cholesterol-lowering effects. We investigated the effects of atorvastatin on the functional and structural properties of blood-brain barrier (BBB) and the activity of astrocytes during the N(omega)-nitro-L-arginine methyl ester (L-NAME) hypertension followed by angiotensin (ANG) II. We found that decreases in concentration of serum catalase and plasma nitric oxide (NO) induced by L-NAME were significantly ameliorated by atorvastatin, whereas L-NAME-induced serum malondialdehyde and cholesterol concentration increases were significantly reduced by atorvastatin. The content of Evans blue (EB) dye significantly increased in cerebellum, left cerebral cortex and diencephalon regions but atorvastatin markedly reduced the increased BBB permeability to EB in the brain regions of animals treated with L-NAME and L-NAME plus ANG II. Brain vessels of L-NAME-treated animals showed a considerable loss of immunoreactivity of tight junction proteins, zonula occludens (ZO)-1 and occludin. Immunoreactivity for ZO-1 and occludin increased in animals treated with atorvastatin and L-NAME plus atorvastatin. Glial fibrillary acidic protein (GFAP) immunoreactivity was seen in few astrocytes in the brain sections of L-NAME, but immunoreactivity for GFAP increased in L-NAME plus atorvastatin-treated animals. We suggest that long-term L-NAME treatment may affect BBB permeability through disruption of tight junction proteins, at least partly, via decreased NO concentration and increased oxidant capacity; the improvement of BBB integrity and astrocytic activity would be more closely associated with the action of atorvastatin favoring the increase in anti-oxidant capacity and expression of tight junction proteins and GFAP.

journal_name

Brain Res

journal_title

Brain research

authors

Kalayci R,Kaya M,Elmas I,Arican N,Ahishali B,Uzun H,Bilgic B,Kucuk M,Kudat H

doi

10.1016/j.brainres.2005.02.044

subject

Has Abstract

pub_date

2005-05-03 00:00:00

pages

184-93

issue

eissn

0006-8993

issn

1872-6240

pii

S0006-8993(05)00295-7

journal_volume

1042

pub_type

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Effects of atorvastatin on blood-brain barrier permeability during L-NAME hypertension followed by angiotensin-II in rats.