The antithrombotic effect of angiotensin-(1-7) closely resembles that of losartan.
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-IC)receiving acute losartan administration (1.39 +/- 0.29 mg vs. 3.25 +/- 0.62 mg; p<0.01). Infusion of Ang-(1-7) to2K-lC 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.
Kucharewicz
I
I
Department of Pharmacodynamics, Medical Academy, Mickiewicza Str.2C, 15-230, Poland. ikuchar@poczta.onet.pl
Chabielska
E
E
Pawlak
D
D
Matys
T
T
Rólkowski
R
R
Buczko
W
W
D000803:Angiotensin I / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003094:Collagen; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006487:Hemostasis / Q000187:drug effects; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D010973:Platelet Adhesiveness / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D020246:Venous Thrombosis / Q000517:prevention & control*
D000959:Antihypertensive Agents; D005343:Fibrinolytic Agents; D010446:Peptide Fragments; D003094:Collagen; D000803:Angiotensin I; C118790:angiotensin I (1-7); D019808:Losartan