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Brain microvascular endothelial cell proliferation with angiotensin stimulation and receptor blockade
Author(s) -
Stingley Cecilia,
Munzenmaier Diane H.
Publication year - 2006
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.20.4.a733-b
Subject(s) - blockade , stimulation , angiotensin receptor , angiotensin ii , cell growth , neuroscience , receptor , microbiology and biotechnology , medicine , chemistry , pharmacology , endocrinology , biology , biochemistry
Aim Hypertension is a major risk factor for stroke. The angiotensin (ANGII) AT 1 receptor antagonist losartan (LOS) is a commonly prescribed hypertension medication. AT 1 receptor activation stimulates angiogenesis in most tissues, yet chronic in vivo blockade of the AT 1 receptor results in angiogenesis in the brain. Since this paradoxical response could be due to alterations in cerebral blood flow rather than direct actions of receptor blockade in the microvessels, this study tested the growth response of human brain microvascular endothelial cells (HBMEC) to ANGII receptor stimulation or blockade in vitro . Methods Cultured HBMEC were exposed to serum‐free media (SFM) alone and in the presence of LOS (10 μM), ANGII (1 μM), or both for 24 hours in 96‐well plates. Cell density was quantified by CyQUANT (Molecular Probes) cell proliferation assay. Results Average fluorescence increased in cells receiving LOS alone (46,358 ± 2771), and was even greater with ANGII stimulation (59,582 ± 7400 ) compared to SFM ( 6,940 ± 168). Results from combined LOS + ANGII stimulation (49,583 ± 3197 ) were not different from LOS treatment alone. Conclusions These data suggest that, unlike in other tissues, AT 1 receptor blockade results in brain endothelial cell proliferation. This supports our previous findings that AT 1 receptor blockade induces cerebral angiogenesis. It is possible that chronic hypertension therapy using ARBs such as losartan might improve brain blood flow through angiogenesis, potentially protecting high‐risk patients from stroke. Supported in part by Frontiers in Physiology Professional Development Fellowship, APS.