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Altered Blood Brain Barrier Integrity in Hypertensive Rats: Role of Angiotensin II.
Author(s) -
Son Sook Jin,
Ahmadi Sahra,
Filosa Jessica A.,
Stern Javier E.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1019.9
Subject(s) - blood–brain barrier , losartan , angiotensin ii , brainstem , endocrinology , medicine , chemistry , dextran , evans blue , renin–angiotensin system , central nervous system , blood pressure , biochemistry
The blood brain barrier (BBB) acts as a physical barrier and a transport mechanism in the CNS, restricting access of systemic harmful chemicals while allowing entrance of essential nutrients. Growing evidence supports compromised BBB integrity under pathological conditions. Here, we aimed to assess if BBB integrity is altered in hypertensive rats. WKY and SHR rats at two developmental stages (7–8 & 11–13 week old) received intracarotid infusions of two fluorescently labeled dyes, RHO‐dextran 70kD and FITC‐dextran 10kD (28 mg/kg.bw, 30 sec). Dyes were allowed to circulate for 20min before the brains were removed, fixed, and processed for confocal imaging. BBB integrity was assessed based on the degree of dye leakage into the extravascular CNS space of hypothalamic and brainstem nuclei. RHO‐70 (larger dye) was largely confined within microvessels, and no differences in extravascular leakage were detected between WKY and SHRs (P>0.5). Conversely, extravascular FITC‐10 mean fluorescence intensity significantly increased in the PVN, NTS and RVLM of SHR compared to WKY rats at both stages (20–200% increase). These changes were largely prevented in SHR rats treated with Losartan (0.2mg/ml, 7 weeks). Our results supports the notion of a disrupted BBB within key CNS areas involved in cardiovascular control in hypertensive rats, and further suggests an AngII‐dependent mechanism. Supported by AHA 0640092N.