Quinapril decreases antifibrinolytic and prooxidative potential of propofol in arterial thrombosis in hypertensive rats

Abstract

Angiotensin converting enzyme inhibitors and propofol both exert hypotensive action and may affect hemostasis. We investigated the influence of quinapril and propofol on hemodynamics and hemostasis in renal-hypertensive rats with induced arterial thrombosis. Two-kidney, one clip hypertensive rats were treated with quinapril (3.0 mg/kg for 10 days), and then received propofol infusion (15 mg/kg/h) during ongoing arterial thrombosis. The hemodynamic and hemostatic parameters were assayed. Quinapril exerted a hypotensive effect increasing after propofol infusion. Quinapril showed an antithrombotic effect with the platelet adhesion reduction, fibrinolysis enhancement and oxidative stress reduction. Propofol did not influence thrombosis; however, it inhibited fibrinolysis and showed prooxidative action. The effect of propofol on fibrinolysis and oxidative stress was significantly lower in quinapril-pretreated rats. Mortality was increased among rats treated with both drugs together. Our study demonstrates that pretreatment with quinapril reduced the adverse effects of propofol on hemostasis. Unfortunately, co-administration of both drugs potentiated hypotension in rats, which corresponds to higher mortality.

Antithrombotic Potential of Tormentil Extract in Animal Models

“…In turn, our earlier studies ( Kramkowski et al, 2006 ; Wojewodzka-Zelezniakowicz et al, 2006 , 2016 ) clearly showed that angiotensin converting enzyme inhibitors (ACE-Is) improve endothelial function in a mechanism involving, among others, BK increase. In the same model of thrombosis, ACE-Is decreased thrombus weight, prolonged the time to carotid artery occlusion, increased blood flow distally to the place of vessel injury and decreased collagen-stimulated whole blood platelet aggregation.…”

“…Furthermore the bleeding time method is used to investigate the primary haemostasis. After vessel wall injury and following vasoconstriction platelets accumulate at the site of the injury to form platelet plug ( Wojewodzka-Zelezniakowicz et al, 2016 ). Prolonged bleeding time clearly indicate the involvement of platelets inhibition in the antithrombotic effect of tormentil extract.…”

“…Rats were anesthetized and placed in a supine position on a heated (37°C) surgical table. The systolic and diastolic blood pressure were measured directly through a cannula filled with heparin solution (150 IU/ml), placed in the left common carotid artery and connected to a pressure transducer (Gabarith 1DT-XX, Poland), and an apparatus for pressure measurement (HSE TRANSONIC, TAM-A, Germany), as described previously ( Wojewodzka-Zelezniakowicz et al, 2016 ).…”

“…Briefly, a standardized device was applied longitudinally on the dorsal part of the tail between 6 and 9 cm from the tip, taking care to avoid the large veins. Immediately after injury, the tail was placed into a cylinder with isotonic saline at 37°C and bleeding time was measured from the moment the tail was surgically cut until bleeding completely stopped (lack of bleeding for < 30 s) ( Wojewodzka-Zelezniakowicz et al, 2016 ).…”

Angiotensin-converting enzyme inhibitors attenuate propofol-induced pro-oxidative and antifibrinolytic effect in human endothelial cells

“…1 Also, an increase in tissue plasminogen activator (t-PA) and decrease in tissue plasminogen activator inhibitor (PAI-1) concentration were observed. 7 …”