title: The acute prothrombotic effect of aldosterone in rats is partially mediated via angiotensin II receptor type 1.
abstract: BACKGROUND
  We showed previously that the prothrombotic effect of one hour aldosterone (ALDO) infusion in rats was only partially mediated by the mineralocorticoid receptor (MR). Bearing in mind that ALDO potentiates the effects of angiotensin II (Ang II), in the present study we investigated the role of Ang II receptor type 1 - AT1 in acute ALDO prothrombotic action.
  
  
  METHODS
  The experiments were performed in a stasis-induced venous thrombosis model in male Wistar, normotensive rats. ALDO (30μg/kg) was infused for 1h. Valsartan (VAL; 10mg/kg), a selective AT1 receptor antagonist, was administered in a single bolus injection before ALDO infusion. Eplerenone (EPL, 100mg/kg), a selective MR receptor antagonist, was administered per os before ALDO. Thrombus weight and incidences of thrombosis were assayed. Bleeding time and platelet adhesion to collagen were evaluated as primary hemostasis parameters. The plasma levels of some coagulation and fibrinolysis parameters, and plasma NO metabolite levels were assayed.
  
  
  RESULTS
  AT1 blockade with valsartan significantly reduced ALDO-induced thrombosis expressed as a reduced thrombus mass (p<0.05 vs ALDO) and diminished the incidence of thrombosis. Valsartan reduced the ALDO-induced changes in bleeding time and platelet adhesion, as well as in coagulation, fibrinolysis, and NO metabolite levels. The effect of AT1 blockade in ALDO-induced thrombosis was similar to the effect of MR blockade. However, dual blockade of AT1 and MR showed no additional benefit.
  
  
  CONCLUSIONS
  ALDO prothrombotic action is partially mediated via AT1 receptor in the mechanism involving enhanced platelet activation, induced coagulation, impaired fibrinolysis and reduced NO bioavailability.
authors.affiliation: Department of Biopharmacy, Medical University of Bialystok, Mickiewicza 2c, 15-089 Bialystok, Poland. Electronic address: anna.gromotowicz@umb.edu.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Gromotowicz-Poplawska
authors.affiliation: Department of Biopharmacy, Medical University of Bialystok, Mickiewicza 2c, 15-089 Bialystok, Poland.
authors.forename: Adrian
authors.initials: A
authors.lastname: Stankiewicz
authors.affiliation: Department of Biopharmacy, Medical University of Bialystok, Mickiewicza 2c, 15-089 Bialystok, Poland.
authors.forename: Karol
authors.initials: K
authors.lastname: Kramkowski
authors.affiliation: Department of Biopharmacy, Medical University of Bialystok, Mickiewicza 2c, 15-089 Bialystok, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Gradzka
authors.affiliation: Department of Emergency Medicine and Disasters, Medical University of Bialystok, Szpitalna 37, 15-295 Bialystok, Poland.
authors.forename: Marzena
authors.initials: M
authors.lastname: Wojewodzka-Zelezniakowicz
authors.affiliation: Department of Human Anatomy, Medical University of Bialystok, Mickiewicza 2a, 15-230 Bialystok, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Dzieciol
authors.affiliation: Department of Medical Biochemistry, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Szemraj
authors.affiliation: Department of Biopharmacy, Medical University of Bialystok, Mickiewicza 2c, 15-089 Bialystok, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Chabielska
mesh_terms: D000450:Aldosterone / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001777:Blood Coagulation; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D020246:Venous Thrombosis / Q000097:blood / Q000378:metabolism* / Q000473:pathology*
chemical_list: D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D000450:Aldosterone
keywords: Aldosterone; Angiotensin II; Hemostasis; Thrombosis; Valsartan