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

Blood
Zia Shariat-MadarA H Schmaier

Abstract

Bradykinin (BK) liberates nitric oxide, prostacyclin, and tissue plasminogen activator from endothelial cells. We hypothesized that BK B2 receptor knockout (KO) mice (BKB2R(-/-)) have increased thrombosis risk. Paradoxically, the BKB2R(-/-) mice have long bleeding times and delayed carotid artery thrombosis, 78 +/- 6.7 minutes, versus 31 +/- 2.7 minutes in controls. 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(-/-) mice have elevated BK 1-5 (160 +/- 75 fmol/mL, vs 44 +/- 29 fmol/mL in controls) and angiotensin II (182 +/- 41 pg/mL, vs 49 +/- 7 pg/mL in controls). Ramipril treatment shortens vessel occlusion time. BKB2R(-/-) mice have elevated plasma 6-keto-PGF1alpha (666 +/- 232 ng/mL, vs 23 +/- 5.3 ng/mL in controls) and serum nitrate (61 +/- 5.3 microM, vs 24 +/- 1.8 microM in controls). Treatment with L-NAME (NG-mono-methyl-L-arginine ester) or nimesulide shortens the thrombosis time. BKB2R(-/-) mice have increased angiotensin receptor 2 (AT2R) mRNA and protein expression. Treatment with an AT2R antagonist, PD123 319, normalizes the thrombosis time and nitrate and...Continue Reading

References

Mar 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·J A OlsonM K Raizada
Jun 29, 1968·Nature·H Y YangT S Chiang
Oct 8, 1999·The Journal of Clinical Investigation·Y TsutsumiT Iwasaka
Mar 15, 2001·American Journal of Physiology. Heart and Circulatory Physiology·Y ZhaoA H Schmaier
Mar 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·D PraticòG A FitzGerald
Feb 7, 2002·The Journal of Biological Chemistry·Zia Shariat-MadarAlvin H Schmaier
Apr 17, 2002·The Journal of Clinical Investigation·Eun D HanAlvin E Davis
Oct 18, 2002·Blood·Ethan J WeissShaun R Coughlin
Jan 23, 2003·Journal of the American Society of Nephrology : JASN·Michael ObstFriedrich C Luft
Feb 25, 2003·American Journal of Physiology. Heart and Circulatory Physiology·Ahmed A K HasanAlvin H Schmaier
Jun 10, 2003·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Alvin H Schmaier
Jun 28, 2003·Proceedings of the National Academy of Sciences of the United States of America·Robson A S SantosThomas Walther
Feb 10, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Yan TanAyad A Jaffa
Mar 5, 2004·Blood·Zia Shariat-MadarAlvin H Schmaier
Jun 24, 2004·The Journal of Pharmacology and Experimental Therapeutics·Marvin T NiemanAlvin H Schmaier
Aug 23, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Z Shariat-MadarA H Schmaier

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Citations

Mar 16, 2011·Journal of Thrombosis and Thrombolysis·Rebecca S WoodruffRichard C Becker
Mar 29, 2007·Nature Clinical Practice. Nephrology·Paolo MadedduSamir El-Dahr
Aug 30, 2008·The Journal of Clinical Investigation·Coen MaasMartijn F B G Gebbink
Aug 30, 2008·The Journal of Clinical Investigation·Alvin H Schmaier
May 21, 2009·Biological Chemistry·Eliete S RodriguesSuma I Shimuta
Apr 25, 2014·Thrombosis Research·Alvin H Schmaier
Nov 14, 2015·Journal of Thrombosis and Haemostasis : JTH·Alvin H Schmaier
Mar 6, 2012·Colloids and Surfaces. B, Biointerfaces·Weixing ShenPeng Liu
Jan 12, 2013·Thrombosis and Haemostasis·Trang T VuJeffrey I Weitz
Sep 22, 2007·Journal of Thrombosis and Haemostasis : JTH·A H Schmaier, K R McCrae
May 23, 2013·Journal of Thrombosis and Haemostasis : JTH·R S WoodruffB A Sullenger
Sep 1, 2015·Pharmacological Reports : PR·Karol KramkowskiWlodzimierz Buczko
Jan 10, 2008·International Immunopharmacology·Elice C BatistaRonaldo C Araújo
Jan 10, 2008·International Immunopharmacology·Alvin H Schmaier
Oct 9, 2012·European Journal of Pharmacology·Bhoomika M Patel, Anita A Mehta
Nov 13, 2012·Blood·Abd Al-Roof Higazi, Douglas B Cines
Feb 24, 2015·Frontiers in Medicine·Alvin H Schmaier
Feb 20, 2015·Hematology·Maurits L van Montfoort, Joost C M Meijers
Jul 6, 2016·Current Opinion in Hematology·Alvin H Schmaier
Jul 13, 2017·Expert Opinion on Therapeutic Patents·Thomas H Graham
Feb 5, 2011·Arteriosclerosis, Thrombosis, and Vascular Biology·Shinsuke NakamuraHideaki Hara
Oct 6, 2007·Arteriosclerosis, Thrombosis, and Vascular Biology·David Gailani, Thomas Renné
Apr 30, 2016·Circulation Research·Jonathan H Foley, Edward M Conway
Mar 3, 2007·Pharmacological Reviews·Noboru TodaTomio Okamura
Jan 20, 2018·Physiological Reviews·Robson Augusto Souza SantosMaria Jose Campagnole-Santos
Jul 25, 2009·Blood·Alec A Schmaier, Alvin H Schmaier
Jun 29, 2007·American Journal of Physiology. Renal Physiology·Yan TanAyad A Jaffa
Aug 22, 2017·Frontiers in Medicine·Fabrício Simão, Edward P Feener
Oct 26, 2010·Life Sciences·Danilo Roman-CamposJader Santos Cruz

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