The expression of P-glycoprotein is increased in vessels with blood-brain barrier impairment in a stroke-prone hypertensive model.
OBJECTIVE
We previously reported that the blood-brain barrier (BBB) function was impaired in vessels in the hippocampus in 3-month-old stroke-prone spontaneously hypertensive rats (SHRSP). In this study, we examined gene and protein expressions of P-glycoprotein, a representative efflux transporter of cerebral vessels, in the BBB-damaged hippocampal vessels of SHRSP and in the vessels of Wistar Kyoto (WKY) rats as controls, to clarify roles of the efflux transporter in the BBB-damaged vessels.


METHODS
The expression of P-glycoprotein in hippocampal and cortical samples was examined by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting and immunoelectron microscopic techniques.


RESULTS
Real-time RT-PCR and Western blotting analyses revealed that the gene and protein expressions of P-glycoprotein were increased in the hippocampal samples of 3-month-old SHRSP compared with hippocampal samples of 3-month-old WKY rats or with cortical samples of SHRSP. The gene expression of P-glycoprotein was also increased in the hippocampal samples of 4-week-old SHRSP. Immunoelectron microscopic examination revealed that immunosignals of P-glycoprotein were seen in the luminal and ab-luminal cytoplasmic membranes of endothelial cells and the basal lamina, that the labelling density of P-glycoprotein in the vessel wall was higher in the hippocampus of 3-month-old SHRSP than in other groups and that the immunosignals of P-glycoprotein were occasionally co-located with those of albumin.


CONCLUSIONS
These findings indicate that the expression of P-glycoprotein is increased in BBB-damaged hippocampal vessels in hypertensive SHRSP compared with those in WKY rats.
Ueno
M
M
Department of Pathology and Host Defense, Kagawa University, Kagawa, Japan. masaueno@med.kagawa-u.ac.jp
Nakagawa
T
T
Huang
C-l
CL
Ueki
M
M
Kusaka
T
T
Hosomi
N
N
Kanenishi
K
K
Onodera
M
M
Wu
B
B
Sakamoto
H
H
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000418:Albumins / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001485:Basement Membrane / Q000502:physiology; D001794:Blood Pressure; D001812:Blood-Brain Barrier / Q000503:physiopathology*; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply* / Q000503:physiopathology*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000502:physiology; D015870:Gene Expression; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D016253:Microscopy, Immunoelectron; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020521:Stroke / Q000503:physiopathology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000418:Albumins