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The antithrombotic effect of captopril and losartan on experimental arterial thrombosis in rats
E Chabielska1, R Pawlak, J Golatowski
1Department of Pharmacodynamics, Medical University of Bialystok, Poland.
Abstract:
The mechanism by which ACE-Is (angiotensin converting enzyme inhibitors) reduces the rate of coronary thrombosis among patients with left ventricular dysfunction is not known. A potential interaction between the renin-angiotensin system (RAS) and the thrombotic process has been suggested. The goal of the present study was to evaluate the antithrombotic action of drugs which block the RAS by different mechanisms; captopril (50 mg/kg p.o.)-the angiotensin converting enzyme inhibitor and losartan (30 mg/kg p.o.)-the selective AT1 receptor antagonist. The normotensive rats were treated in acute or chronic manner (7 days) and then the arterial thrombosis was induced by insertion of a loop-shaped cannula into the abdominal aorta. The occlusion time (the period during which the loop was totally occluded by thrombus) was significantly prolonged in comparison with the control groups after chronic treatment with captopril (by 46%; p < 0.01) and losartan (by 42%; p < 0.05). Our results provide experimental evidence that the drugs blocking RAS exert an antithrombotic effect in the arterial thrombosis model in rats. This effect was independent from changes in blood pressure and primary hemostasis.
Insights
Angiotensin converting enzyme inhibitors and AT1 receptor antagonists, which block the renin-angiotensin system, demonstrate significant antithrombotic effects in a rat arterial thrombosis model. These findings suggest a role for the renin-angiotensin system in thrombosis independent of blood pressure.
Area of Science:
- Cardiovascular Pharmacology
- Thrombosis Research
- Renin-Angiotensin System (RAS)
Background:
- The mechanism of coronary thrombosis reduction by ACE inhibitors in left ventricular dysfunction is unclear.
- A link between the renin-angiotensin system (RAS) and thrombotic processes is hypothesized.
Purpose of the Study:
- To investigate the antithrombotic potential of RAS-blocking drugs.
- To evaluate captopril (ACE inhibitor) and losartan (AT1 receptor antagonist) in an arterial thrombosis model.
Main Methods:
- Normotensive rats received acute or chronic (7-day) treatment with captopril or losartan.
- Arterial thrombosis was induced via aortic cannula insertion.
- Occlusion time, indicating thrombus formation, was measured.
Main Results:
- Chronic captopril treatment significantly prolonged occlusion time by 46% (p < 0.01).
- Chronic losartan treatment significantly prolonged occlusion time by 42% (p < 0.05).
- Antithrombotic effects were observed irrespective of blood pressure or primary hemostasis changes.
Conclusions:
- Drugs blocking the renin-angiotensin system exhibit significant antithrombotic activity in rats.
- This antithrombotic effect is independent of alterations in blood pressure and primary hemostasis.
- The RAS plays a role in arterial thrombosis.