Angiotensin II enhances thrombosis development in renovascular hypertensive rats.
There is an increased number of in vitro evidence that angiotensin II (Ang II) may promote thrombosis. However there are no in vivo experiments exploring the effect of Ang II on thrombus formation. In the present study we have investigated the influence of Ang II on venous thrombosis in renovascular hypertensive rats. Furthermore, we examined the role of AT(1) receptor and Ang II metabolites: angiotensin III (Ang III) and angiotensin IV (Ang IV) in the mechanisms of Ang II action. The contribution of coagulation and fibrinolytic systems in the mode of Ang II action was also determined. Venous thrombosis was induced by ligation of vena cava. Ang II infused into rats developing venous thrombosis caused dose-dependent increase in thrombus weight, which was partially reversed by losartan, selective AT(1) antagonist. Ang III did not influence the thrombus formation in hypertensive rats, while Ang IV caused a marked increase in thrombus weight only in one of the used doses. Our study shows that Ang II via AT(1) receptor enhances thrombosis development. The prothrombotic effect of Ang II may partially depend on enhanced leukocytes adhesion to endothelial cells accompanied by accelerated fibrin formation and increased plasma level of PAI-1. Moreover, Ang II action is partially mediated by one of its metabolites - Ang IV.
Mogielnicki
Andrzej
A
Department of Pharmacodynamics, Medical University, Mickiewicza Str. 2C, 15-089 Bialystok, Poland.
Chabielska
Ewa
E
Pawlak
Robert
R
Szemraj
Janusz
J
Buczko
Wlodzimierz
W
D000804:Angiotensin II / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D000805:Angiotensin III / Q000008:administration & dosage; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects / Q000503:physiopathology; D005337:Fibrin / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006978:Hypertension, Renovascular / Q000150:complications* / Q000503:physiopathology; D007262:Infusions, Intravenous; D019808:Losartan / Q000008:administration & dosage; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000502:physiology; D011994:Recombinant Proteins / Q000008:administration & dosage; D012039:Regional Blood Flow / Q000187:drug effects; D010959:Tissue Plasminogen Activator / Q000097:blood; D020246:Venous Thrombosis / Q000209:etiology* / Q000503:physiopathology; D000979:alpha-2-Antiplasmin / Q000378:metabolism
D047228:Angiotensin II Type 1 Receptor Blockers; D017395:Plasminogen Activator Inhibitor 1; D044140:Receptor, Angiotensin, Type 1; D011994:Recombinant Proteins; D000979:alpha-2-Antiplasmin; D000804:Angiotensin II; D000805:Angiotensin III; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; D005337:Fibrin; D010959:Tissue Plasminogen Activator; D019808:Losartan