title: Study of the mechanisms of aldosterone prothrombotic effect in rats.
abstract: BACKGROUND
  We investigated the role of primary haemostasis, fibrinolysis, nitric oxide (NO) and oxidative stress as well as mineralocorticoid receptors (MR) in acute aldosterone prothrombotic action.
  
  
  METHODS
  Venous thrombosis was induced by stasis in Wistar rats. Aldosterone (ALDO; 10, 30, 100 µg/kg/h) was infused for 1 h. Eplerenone (EPL; 100 mg/kg, p.o.), a selective MR antagonist, was administered before ALDO infusion. Bleeding time (BT) and platelet adhesion to collagen were evaluated. The expression of nitric oxide synthase (NOS), NADPH oxidase, superoxide dismutase (SOD) and plasminogen activator inhibitor (PAI-1) was measured. NO, malonyl dialdehyde (MDA) and hydrogen peroxide (H(2)O(2)) plasma levels were assayed.
  
  
  RESULTS
  Significant enhancement of venous thrombosis was observed after ALDO infusion. ALDO shortened BT and increased platelet adhesion. Marked increases were observed in PAI-1, NADPH oxidase and SOD mRNA levels. MDA and H(2)O(2) levels were augmented in ALDO-treated groups, and NOS expression and NO level were decreased. EPL reduced ALDO effects on thrombus formation, primary haemostasis, PAI-1 expression and MDA level.
  
  
  CONCLUSIONS
  Short-term ALDO infusion enhances experimental venous thrombosis in the mechanism involving primary haemostasis, fibrinolysis, NO and oxidative stress-dependent pathways. The MR antagonist only partially diminished the ALDO effects, suggesting the involvement of additional mechanisms.
authors.affiliation: Medical University of Bialystok, Department of Biopharmacy, Poland. biofarm@umwb.edu.pl
authors.forename: Anna
authors.initials: A
authors.lastname: Gromotowicz
authors.forename: Janusz
authors.initials: J
authors.lastname: Szemraj
authors.forename: Adrian
authors.initials: A
authors.lastname: Stankiewicz
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Zakrzeska
authors.forename: Maria
authors.initials: M
authors.lastname: Mantur
authors.forename: Ewa
authors.initials: E
authors.lastname: Jaroszewicz
authors.forename: Franciszek
authors.initials: F
authors.lastname: Rogowski
authors.forename: Ewa
authors.initials: E
authors.lastname: Chabielska
mesh_terms: D000450:Aldosterone / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D001682:Biological Availability; D001760:Bleeding Time; D006439:Hemodynamics / Q000187:drug effects; D006487:Hemostasis; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists; D009569:Nitric Oxide / Q000097:blood; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D010973:Platelet Adhesiveness / Q000187:drug effects; D011188:Potassium / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D013927:Thrombosis / Q000097:blood / Q000473:pathology* / Q000503:physiopathology / Q000652:urine; D020246:Venous Thrombosis / Q000473:pathology
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D017395:Plasminogen Activator Inhibitor 1; D018161:Receptors, Mineralocorticoid; D009569:Nitric Oxide; D000450:Aldosterone; D019001:Nitric Oxide Synthase; D011188:Potassium