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The antithrombotic effect of angiotensin-(1—7) closely resembles that of losartan

Department of Pharmacodynamics, Medical Academy in Bialystok, Poland, ikuchar@ poczta.onet.pl

Ewa Chabielska

Department of Pharmacodynamics, Medical Academy in Bialystok, Poland

Dariusz Pawlak

Department of Pharmacodynamics, Medical Academy in Bialystok, Poland

Tomasz Matys

Department of Pharmacodynamics, Medical Academy in Bialystok, Poland

Roland Rólkowski

Department of Laboratory Diagnostics, Regional Centre of Oncology, Bialystok, Poland

Wlodzimierz Buczko

Department of Pharmacodynamics, Medical Academy in Bialystok, Poland

Angiotensin-(1-7) [Ang-(1-7)] is the bioactive peptide which may be responsible for some of the pharmacological effects of losartan. Our previous study has demonstrated the antithrombotic action of losartan in a model of experimental thrombosis. In the present study, we compared the antithrombotic action of losartan and Ang-(1-7).

Acute (10 mg/kg, p.o.) and chronic (10 mg/kg, p.o., three weeks) losartan administration to spontaneously hypertensive rats (SHR) induced a decrease in thrombus weight (1.6±0.6 mg and 1.2±0.3 mg respectively vs. control 2.9±0.8 mg; p<0.05, p<0.05). A similar reduction was observed in two-kidney, one-clip hypertensive rats (2K-1C) receiving acute losartan administration (1.39±0.29 mg vs. 3.25±0.62 mg; p<0.01). Infusion of Ang-(1-7) to 2K-1C rats also reduced the thrombus weight (1.01±0.34 mg, 1.23±0.38 mg and 2.17±0.36 mg for 1, 10, 100 pmol/kg/min, respectively vs. 3.58±0.6 mg control; p<0.01, p<0.01, p<0.05). Losartan produced a decrease in systolic blood pressure (BP) in SHR as well as in 2K-1C rats, while Ang-(1-7) infusion had no effect on BP. Acute losartan dosing to 2K-1C rats decreased platelet adhesion to fibrillar collagen (24.9±1.0% vs. control 31.5±1.1%, p<0.001). The incubation of platelet samples with Ang-(1-7) (10^-6 and 10 ^—5 M) also reduced adhesion to fibrillar collagen (38.4±0.1% and 33.8±0.8% respectively vs. control 40.0±0.6%; p<0.05, p<0.001). There were no apparent changes in prothrombin time, activated partial thromboplastin time and euglobulin clot lysis time in losartan and Ang-(1-7)-treated groups. We conclude that, like losartan, Ang-(1-7) is able to act as an antithrombotic agent.

Key Words: losartan • angiotensin-(1-7) • venous thrombosis

Journal of Renin-Angiotensin-Aldosterone System, Vol. 1, No. 3, 268-272 (2000)
DOI: 10.3317/jraas.2000.041


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