Zobraziť v EDS

Aliskiren inhibits experimental venous thrombosis in two-kidney one- clip hypertensive rats

Uložené v:
Podrobná bibliografia
Názov: Aliskiren inhibits experimental venous thrombosis in two-kidney one- clip hypertensive rats
Autori: Agnieszka Leszczynska, Justyna Magdalena Hermanowicz, Adam Hermanowicz, Piotr Buczko, Andrzej Mogielnicki, Anna Tankiewicz-Kwedlo, Wlodzimierz Buczko
Zdroj: Thrombosis Research. 131:e39-e44
Informácie o vydavateľovi: Elsevier BV, 2013.
Rok vydania: 2013
Predmety: Male, 0301 basic medicine, Dose-response relationship, Enzyme inhibitors - pharmacology, Venous thrombosis - etiology, Wistar, Venous thrombosis - drug therapy, Administration, Oral, Blood Pressure, renovascular - etiology, Kidney, Fibrinolytic agents - administration & dosage, Nitric oxide - metabolism, Fibrinolysis - drug effects, Biomarkers - blood, oral, Amides - pharmacology, 0302 clinical medicine, Fumarates, renovascular - blood, renovascular - drug therapy, animal, Nitric oxide synthase - metabolism, Enzyme Inhibitors, Nitric oxide synthase - antagonists & inhibitors, Tissue plasminogen activator - blood, Fibrinolysis, drug, 3. Good health, Hypertension, Renovascular, Hypoglycemic agents - pharmacology, Administration, Fumarates - pharmacology, Hypertension, Blood platelets - metabolism, Blood Platelets, Disease models, renovascular - physiopathology, Nitric Oxide, Venous thrombosis - blood, Blood platelets - drug effects, renovascular - metabolism, 03 medical and health sciences, Fibrinolytic Agents, Kidney - blood supply, Animals, Hypoglycemic Agents, Fibrinolytic agents - pharmacology, Plasminogen activator inhibitor 1 - blood, Ligation, Dose-Response Relationship, Drug, Fumarates - administration & dosage, Blood pressure - drug effects, Renal artery - surgery, Amides, Epoprostenol, Rats, Platelet activation - drug effects, Disease Models, Animal, Epoprostenol - metabolism, Hypoglycemic agents - administration & dosage, Venous thrombosis - metabolism, Nitric Oxide Synthase, Amides - administration & dosage, Biomarkers
Popis: 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.
Druh dokumentu: Article
Jazyk: English
ISSN: 0049-3848
DOI: 10.1016/j.thromres.2012.11.001
Prístupová URL adresa: https://pubmed.ncbi.nlm.nih.gov/23174623
https://pubmed.ncbi.nlm.nih.gov/23174623/
https://www.sciencedirect.com/science/article/pii/S0049384812008006
http://www.sciencedirect.com/science/article/pii/S0049384812008006
Rights: Elsevier TDM
Prístupové číslo: edsair.doi.dedup.....d18dbaf956895d760bf4bffb4590b460
Databáza: OpenAIRE
Popis
Abstrakt: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.
ISSN:00493848
DOI:10.1016/j.thromres.2012.11.001