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Role of AT1‐receptors in hypercholesterolemia‐induced thrombosis.
Author(s) -
Russell Janice M,
Granger D. Neil
Publication year - 2009
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.23.1_supplement.593.16
Subject(s) - thrombus , losartan , thrombosis , medicine , arteriole , angiotensin ii receptor type 1 , microcirculation , endocrinology , angiotensin ii , receptor
Hypercholesterolemia is associated with increased platelet aggregation and increased risk for thrombosis. Previous reports have described the ability of diet‐induced hypercholesterolemia (HC) to enhance thromboembolism in arterioles, but not venules, in rabbit mesentery (Broeders; ATBV 22:680, 2002). The objectives of this study were to determine whether: 1) HC promotes thrombus formation in microvessels of mouse cremaster muscle and 2) angiotensin II type‐1 receptors (AT1‐R) mediate the HC‐induced responses. Intravital videomicroscopy was used to monitor thrombus formation induced with a light/dye endothelial injury model in mice placed on either a normal diet (ND), 2 wks high‐cholesterol diet (HCD) or HCD mice treated with the AT1‐R antagonist, losartan (25mg/kg/day) in drinking water for 7 days. Arterioles in HCD mice exhibited an enhanced rate of thrombus formation compared to ND mice, decreasing the time of thrombus onset and the time to flow cessation. As previously reported, light/dye‐induced thrombosis was not altered in venules of HCD mice. The HCD‐enhanced thrombosis in arterioles was not altered by losartan treatment. These findings confirm the vulnerability of arterioles to HC‐induced thrombosis, and indicate that mechanisms other than AT1‐R activation underlie the increased risk for thrombosis during hypercholesterolemia. (Supported by HL26441).