Antithrombotic effect of tissue and plasma type angiotensin converting enzyme inhibitors in experimental thrombosis in rats

J Physiol Pharmacol. 2006 Jun;57(2):231-45.

Abstract

This study compared the antithrombotic effect of plasma angiotensin converting enzyme inhibitors (ACE-Is): captopril (CAP), enalapril (ENA) and tissue ACE-Is: perindopril (PER), quinapril (QUIN) in experimental venous and arterial thrombosis. Normotensive Wistar rats were treated p.o. with CAP (75 mg/kg), ENA (20 mg/kg), PER (2 mg/kg) and QUIN (3 mg/kg) for 10 days. The influence of ACE-Is on coagulation and fibrinolytic systems as well as platelet function was evaluated. The hypotensive effect of ACE-Is was equal in all groups. QUIN maintained the final carotid blood flow at the highest value in comparison to PER and plasma ACE-Is. The arterial thrombus weight was reduced in PER and QUIN groups while venous thrombus weight was also reduced after CAP. Tissue and plasma ACE-Is caused the inhibition of platelet adhesion and aggregation. A reduction of fibrin generation, prolongation of prothrombin time (PT), activated partial thromboplastin time (APTT) and shortening of euglobulin clot lysis time (ECLT) were observed after PER and QUIN treatment. In conclusion, given in equipotent hypotensive doses, tissue ACE-Is exerted more pronounced antithrombotic effect than plasma ACE-Is in experimental thrombosis. The differences between tissue and plasma ACE-Is in terms of their more pronounced inhibition of experimental thrombosis may be related to the intensified activation of fibrinolysis and inhibition of coagulation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / classification
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Animals
  • Blood Pressure / drug effects
  • Captopril / pharmacology
  • Captopril / therapeutic use
  • Carotid Arteries / physiopathology
  • Disease Models, Animal
  • Enalapril / pharmacology
  • Enalapril / therapeutic use
  • Fibrillar Collagens / pharmacology
  • Fibrin / biosynthesis
  • Hemostasis / drug effects
  • Male
  • Perindopril / pharmacology
  • Perindopril / therapeutic use
  • Platelet Adhesiveness / drug effects
  • Platelet Aggregation / drug effects
  • Quinapril
  • Rats
  • Rats, Wistar
  • Regional Blood Flow / drug effects
  • Tetrahydroisoquinolines / pharmacology
  • Tetrahydroisoquinolines / therapeutic use
  • Thromboembolism / blood
  • Thromboembolism / drug therapy*

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Fibrillar Collagens
  • Tetrahydroisoquinolines
  • Enalapril
  • Fibrin
  • Captopril
  • Quinapril
  • Perindopril