increased nitric oxide and prostacyclin Bradykinin B2 receptor knockout mice are protected from thrombosis by

ABSTRACT Bradykinin (BK) liberates nitric oxide, prostacyclin, and tissue plasminogen activator from endothelial cells. We hypothesized that BK B2 receptor KO mice (BKB2R-/-) have increased thrombosis risk. Paradoxically, the BKB2R-/- have long bleeding times and delayed carotid artery thrombosis, 78±6.7 min vs 31±2.7 min control. The mechanism(s) for thrombosis protection was sought. In BKB2R-/- plasma coagulation, fibrinolysis and anticoagulant proteins are normal except for an increased prekallikrein and decreased factor XI. BKB2R-/- have elevated BK 1-5, (160±75 fmol/ml vs 44±29 fmol/ml control) and angiotensin II (182±41 pg/ml vs 49±7 pg/ml control). Ramipril treatment shortens vessel occlusion time. BKB2R-/- have elevated plasma 6-keto-PGF 1α (666±232 ng/ml vs 23±5.3 ng/ml control) and serum nitrate (61±5.3 μ M vs 24±1.8 μ M control). Treatment with L-NAME or nimesulide shortens the thrombosis time. BKB2R-/- have increased angiotensin receptor 2 (AT 2 R) mRNA and protein expression. Treatment with an AT