title: Aliskiren inhibits experimental venous thrombosis in two-kidney one- clip hypertensive rats.
abstract: A substantial amount of evidence links the renin-angiotensin system with thrombosis. For example, ACE inhibitors and angiotensin receptor blockers possess independent of the hemodynamic changes, antithrombotic activity. Aliskiren direct renin inhibitor belongs to a new very promising antihypertensive drug that effectively inhibits the renin-angiotensin system. The aim of study was to determine the influence of aliskiren on stasis-induced venous thrombosis in renovascular hypertensive and normotensive rats. The involvement of nitric oxide and prostacyclin in the potential antithrombotic action was also elucidated. Six weeks after clipping of the left renal artery rats developed hypertension which was confirmed by the "tail cuff" method. Hypertensive and normotensive rats were treated with aliskiren (10, 30 and 100mg/kg/day) per os for 10days. Venous thrombosis was induced by stasis of vena cava inferior. Aliskiren at the highest dose induced a significant decrease in systolic blood pressure in hypertensive, but did not change this parameter in normotensive rats. Oral administration of aliskiren resulted in dose-dependent decrease of venous thrombus weight in hypertensive and normotensive rats. The antithrombotic activity of aliskiren was abolished both by NO synthase inhibitor and prostacyclin synthesis inhibitor. Aliskiren decreased collagen-induced platelet aggregation, increased plasma level of tissue plasminogen activator activity whereas no changes in plasminogen activator inhibitor activity and coagulation parameters were found. We showed that aliskiren prevents the development of venous thrombosis by enhanced fibrinolysis and the blood platelet inhibition via nitric oxide and/or prostacyclin-dependent mechanism.
authors.affiliation: Department of Pharmacodynamics, Medical University of Bialystok, Poland. justyna.hermanowicz@umb.edu.pl
authors.forename: Justyna Magdalena
authors.initials: JM
authors.lastname: Hermanowicz
authors.forename: Adam
authors.initials: A
authors.lastname: Hermanowicz
authors.forename: Piotr
authors.initials: P
authors.lastname: Buczko
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Leszczynska
authors.forename: Anna
authors.initials: A
authors.lastname: Tankiewicz-Kwedlo
authors.forename: Andrzej
authors.initials: A
authors.lastname: Mogielnicki
authors.forename: Wlodzimierz
authors.initials: W
authors.lastname: Buczko
mesh_terms: D000284:Administration, Oral; D000577:Amides / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D005650:Fumarates / Q000008:administration & dosage / Q000494:pharmacology*; D006978:Hypertension, Renovascular / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply*; D008026:Ligation; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D015539:Platelet Activation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012077:Renal Artery / Q000601:surgery*; D010959:Tissue Plasminogen Activator / Q000097:blood; D020246:Venous Thrombosis / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism
chemical_list: D000577:Amides; D015415:Biomarkers; D004791:Enzyme Inhibitors; D005343:Fibrinolytic Agents; D005650:Fumarates; D007004:Hypoglycemic Agents; D017395:Plasminogen Activator Inhibitor 1; D009569:Nitric Oxide; C446481:aliskiren; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D010959:Tissue Plasminogen Activator