Oral warfarin and the thrombin inhibitor dabigatran increase blood pressure in rats: Hidden danger of anticoagulants?

American Journal of Hypertension

Volumn 28, Issue 2, 2015, Pages 182-189

  Ware, Kyle M ^a   Vance, Jay C ^b   Muni, Navin ^a   Hebert, Lee A ^b   Satoskar, Anjali A ^a   Nadasdy, Gyongyi ^a   Ivanov, Iouri ^a   Nadasdy, Tibor ^a   Rovin, Brad H ^b   Brodsky, Sergey V ^a  

^a OHIO STATE UNIVERSITY   (United States)

^b THE OHIO STATE UNIVERSITY WEXNER MEDICAL CENTER   (United States)

Author keywords

5 6 nephrectomy; Blood pressure; chronic kidney injury; dabigatran; hypertension; warfarin

Indexed keywords

1 AMINO 3 CYCLOPROPYLAMINO 7 (4 ISOPROPYLBENZYL) 7H PYRROLO[3,2 F]QUINAZOLINE; ACETYLCYSTEINE; DABIGATRAN; VITAMIN K GROUP; WARFARIN; ANTICOAGULANT AGENT; ANTIFIBRINOLYTIC AGENT; ANTITHROMBIN; BENZIMIDAZOLE DERIVATIVE; BETA ALANINE; N3-CYCLOPROPYL-7-((4-(1-METHYLETHYL)PHENYL)METHYL)-7H-PYRROLO(3, 2-F)QUINAZOLINE-1,3-DIAMINE; PROTEINASE ACTIVATED RECEPTOR 1; PYRROLE DERIVATIVE; QUINAZOLINE DERIVATIVE; SCAVENGER;

ANIMAL EXPERIMENT; ANTICOAGULANT THERAPY; ARTICLE; BLOOD CLOTTING TEST; BLOOD PRESSURE MEASUREMENT; CHRONIC KIDNEY DISEASE; CONTROLLED STUDY; DOSE RESPONSE; ELEVATED BLOOD PRESSURE; INTERNATIONAL NORMALIZED RATIO; KIDNEY FUNCTION; MALE; NEPHRECTOMY; NONHUMAN; PRIORITY JOURNAL; PROTHROMBIN TIME; RAT; SYSTOLIC BLOOD PRESSURE; WEIGHT CHANGE; ANALOGS AND DERIVATIVES; ANIMAL; ANTAGONISTS AND INHIBITORS; BLOOD PRESSURE; CHRONIC KIDNEY FAILURE; DISEASE MODEL; DRUG EFFECTS;

ACETYLCYSTEINE; ANIMALS; ANTICOAGULANTS; ANTIFIBRINOLYTIC AGENTS; ANTITHROMBINS; BENZIMIDAZOLES; BETA-ALANINE; BLOOD PRESSURE; DISEASE MODELS, ANIMAL; DOSE-RESPONSE RELATIONSHIP, DRUG; FREE RADICAL SCAVENGERS; NEPHRECTOMY; PYRROLES; QUINAZOLINES; RATS; RECEPTOR, PAR-1; RENAL INSUFFICIENCY, CHRONIC; VITAMIN K; WARFARIN;

EID: 84922519482     PISSN: 08957061     EISSN: 19417225     Source Type: Journal    
DOI: 10.1093/ajh/hpu129     Document Type: Article

References (31)

1. Brodsky S V, Nadasdy T, Rovin BH, Satoskar AA, Nadasdy GM, Wu HM, Bhatt UY, Hebert LA. Warfarin-related nephropathy occurs in patients with and without chronic kidney disease and is associated with an increased mortality rate. Kidney Int 2011; 80:181-189.
2. Brodsky S V, Satoskar A, Chen J, Nadasdy G, Eagen J W, Hamirani M, Hebert L, Calomeni E, Nadasdy T. Acute kidney injury during warfarin therapy associated with obstructive tubular red blood cell casts: a report of 9 cases. Am J Kidney Dis 2009; 54:1121-1126.
3. Brodsky S V, Collins M, Park E, Rovin BH, Satoskar AA, Nadasdy G, Wu H, Bhatt U, Nadasdy T, Hebert LA. Warfarin therapy that results in an international normalization ratio above the therapeutic range is associated with accelerated progression of chronic kidney disease. Nephron Clin Prac 2010; 115:c142-c146.
4. Ozcan A, Ware K, Calomeni E, Nadasdy T, Forbes R, Satoskar AA, Nadasdy G, Rovin BH, Hebert LA, Brodsky S V. 5/6 nephrectomy as a validated rat model mimicking human warfarin-related nephropathy. Am J Nephrol 2012; 35:356-364.
5. Ware K, Brodsky P, Satoskar AA, Nadasdy T, Nadasdy G, Wu H, Rovin BH, Bhatt U, Von Visger J, Hebert LA, Brodsky S V. Warfarin-related nephropathy modeled by nephron reduction and excessive anticoagu-lation. J Am Soc Nephrol 2011; 22:1856-1862.
6. Ryan M, Ware K, Qamri Z, Satoskar A, Wu H, Nadasdy G, Rovin B, Hebert L, Nadasdy T, Brodsky S V. Warfarin-related nephropathy is the tip of the iceberg: direct thrombin inhibitor dabigatran induces glomerular hemorrhage with acute kidney injury in rats. Nephrol Dial Transplant, published online 5 September 2013.
7. Manolis A, Doumas M, Poulimenos L, Kallistratos M, Mancia G. The unappreciated importance of blood pressure in recent and older atrial fbrillation trials. J Hypertens 2013; 31:2109-2117; discussion 2117.
8. Ware K, Qamri Z, Ozcan A, Satoskar AA, Nadasdy G, Rovin BH, Hebert LA, Nadasdy T, Brodsky S V. N-acetylcysteine ameliorates acute kidney injury but not glomerular hemorrhage in an animal model of warfarin-related nephropathy. Am J Physiol Renal Physiol 2013; 304:F1421-F1427.
9. Poller L, Keown M, Ibrahim S, Lowe G, Moia M, Turpie AG, Roberts C, van den Besselaar AM, van der Meer FJ, Tripodi A, Palareti G, Jespersen J. A multicentre randomised clinical endpoint study of PARMA 5 computer-assisted oral anticoagulant dosage. Brit J Haematol 2008; 143:274-283.
10. Liu C, Wan J, Yang Q, Qi B, Peng W, Chen X. Efects of atorvasta-tin on warfarin-induced aortic medial calcifcation and systolic blood pressure in rats. J Huazhong Univ Sci Technolog Med Sci 2008; 28:535-538.
11. Krishnan S, Chawla N, Ezekowitz MD, Peixoto AJ. Warfarin therapy and systolic hypertension in men with atrial fbrillation. Am J Hypertens 2005; 18:1592-1599.
12. Dao HH, Essalihi R, Graillon JF, Lariviere R, De Champlain J, Moreau P. Pharmacological prevention and regression of arterial remodeling in a rat model of isolated systolic hypertension. J Hypertens 2002; 20:1597-1606.
13. Essalihi R, Dao HH, Yamaguchi N, Moreau P. A new model of isolated systolic hypertension induced by chronic warfarin and vitamin K1 treatment. Am J Hypertens 2003; 16:103-110.
14. Lim MA, Shafque S, See SY, Khan FN, Parikh CR, Peixoto AJ. Efects of warfarin on blood pressure in men with diabetes and hypertension-a longitudinal study. J Clin Hypertens 2007; 9:256-258.
15. Mandal AK, Lyden T W, Saklayen MG. Heparin lowers blood pressure: biological and clinical perspectives. Kidney Int 1995; 47:1017-1022.
16. Susic D, Mandal AK, Jovovic D, Veljkovic V, Panajotovic V, Bell RD, Kentera D. The efect of acute and chronic hematocrit changes on cardiovascular hemodynamics in spontaneously hypertensive rats. Am J Hypertens 1992; 5:713-718.
17. Vasdev S, Prabhakaran V, Sampson CA. Heparin lowers blood pressure and vascular calcium uptake in hypertensive rats. Scan J Clin Lab Invest 1991; 51:321-327.
18. Susic D, Mandal AK, Kentera D. Heparin lowers the blood pressure in hypertensive rats. Hypertension 1982; 4:681-685.
19. Wilson SK, Solez K, Boitnott JK, Heptinstall RH. The efects of heparin treatment on hypertension and vascular lesions in stroke-prone spontaneously hypertensive rats. Am J Pathol 1981; 102:62-71.
20. Eisert WG, Hauel N, Stangier J, Wienen W, Clemens A, van Ryn J. Dabigatran: an oral novel potent reversible nonpeptide inhibitor of thrombin. Arterioscler Tromb Vasc Biol 2010; 30:1885-1889.
21. Coughlin SR. Protease-activated receptors in hemostasis, thrombosis and vascular biology. J Trom Haemost 2005; 3:1800-1814.
22. Coughlin SR. Protease-activated receptors in vascular biology. Tromb Haemost 2001; 86:298-307.
23. Glusa E. Trombin induces endothelium-dependent relaxation of pig coronary arteries. Folia Haematologica 1988; 115:101-105.
24. Inoue Y, Tomita T, Nakamura K, Ezaki M, Nakayama K. Trombin-induced endothelium-dependent relaxation and its inhibition by LDL in porcine coronary arteries. Chem Pharm Bull 1988; 36:4626-4629.
25. Ku DD, Zaleski JK. Receptor mechanism of thrombin-induced endothelium-dependent and endothelium-independent coronary vascular efects in dogs. J Cardiovasc Pharmacol 1993; 22:609-616.
26. Winn MJ, Ku DD, Nelson JM. Inhibition of thrombin-induced endothe-lium-dependent relaxation afer coronary ischemia in the dog: possible role of the coagulation cascade. J Cardiovasc Pharmacol 1991; 18:68-76.
27. Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet 2008; 47:285-295.
28. Favaloro EJ, Lippi G. Laboratory testing and/or monitoring of the new oral anticoagulants/antithrombotics: for and against? Clin Chem Lab Med 2011; 49:755-757.
29. Wienen W, Stassen JM, Priepke H, Ries UJ, Hauel N. In-vitro profle and ex-vivo anticoagulant activity of the direct thrombin inhibitor dabigatran and its orally active prodrug, dabigatran etexilate. Tromb Haemost 2007; 98:155-162.
30. Takahashi H, Yoshika M, Komiyama Y, Nishimura M. The central mechanism underlying hypertension: a review of the roles of sodium ions, epithelial sodium channels, the renin-angiotensin-aldosterone system, oxidative stress and endogenous digitalis in the brain. Hypertens Res 2011; 34:1147-1160.
31. Wilcox CS. Asymmetric dimethylarginine and reactive oxygen species: unwelcome twin visitors to the cardiovascular and kidney disease tables. Hypertension 2012; 59:375-381.