fibrin and Hypertension--Renovascular

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.

Topics: alpha-2-Antiplasmin; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin III; Animals; Blood Pressure; Carotid Arteries; Fibrin; Heart Rate; Hypertension, Renovascular; Infusions, Intravenous; Losartan; Male; Plasminogen Activator Inhibitor 1; Rats; Rats, Wistar; Receptor, Angiotensin, Type 1; Recombinant Proteins; Regional Blood Flow; Tissue Plasminogen Activator; Venous Thrombosis

Malignant renal hypertension was induced in male Wistar rats. In the early phase of the disease, ie. the 1st week, a transient and generalized activation of arterial cellular functions was observed, while later, on day 21 widespread intimal proliferations developed in the arteries. This early activation included an increase in transmural permeability, DNA-, protein, collagen, elastin and ground substance synthesis, a rise in mural PGI2 content and an increase in number of Weibel-Palade bodies. An activation of platelets and monocytes could also be detected during the 1st week. In a group of rats the development of malignant hypertension was interrupted following the early activation of arteries and the incidence of intimal proliferations was compared with that of rats with maintained hypertension. No intimal proliferation was observed on day 21 in the rats with interrupted hypertension. It is concluded that the early activation of the artery does not furnish enough stimulus for triggering intimal proliferations and intimal plaques are not direct sequelae of the early arterial reaction. Furthermore the entrance of plasma materials during transmural permeability increase can not induce smooth muscle proliferation if the hypertension is interrupted.

Topics: Animals; Aorta; Arteries; Arterioles; Cell Membrane Permeability; Endothelium; Fibrin; Hypertension, Renovascular; Hypertrophy; Iron; Male; Microscopy, Electron; Muscle, Smooth, Vascular; Necrosis; Rats; Rats, Inbred Strains; Renin