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The antithrombotic effect of angiotensin-(1—7) closely resembles that of losartan
Iwona Kucharewicz
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
References
- Cachofeiro V., Maeso R., Rodrigo E., Navarro J., Ruilope LM, Lahera V. Nitric oxide and prostacyclin in the prolonged effects of losartan and ramipril in hypertension. Hypertension 1995; 26: 236-43.[Abstract/Free Full Text]
- Ardaillou R. Angiotensin II receptors. J Am Soc Nephrol 1999; 10: S30-S39.[Web of Science][Medline]
[Order article via Infotrieve]
- McIntyre M., Caffe SA, Michalak RA, Reid JL Losartan, an orally active angiotensin (AT1) receptor antagonist: a review of its efficacy and safety in essential hypertension. Pharmacol Ther 1997; 74:181-94.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Pitt B., Segal R., Martinez FA et al. Randomised trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE). Lancet 1997; 349: 747-52.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Pitt B., Poole-Wilson PA, Segale R. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial - the Losartan Heart Failure Survival Study ELITE II. Lancet 2000; 355: 1582-87.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Iyer SN, Chappell MC, Averill DB, Diz DI, Ferrario CM Vasodepressor actions of angiotensin-(1-7) unmasked during combined treatment with lisinopril and losartan. Hypertension 1998; 31: 669-705.
- Ferrario CM, Chappell MC, Tallant EA, Brosnihan KB, Diz DI Counterregulatory actions of angiotensin-(1-7). Hypertension 1997; 30: 535-41.[Abstract/Free Full Text]
- Chabielska E., Pawlak R., Golatowski J., Rólkowski R., Buczko W. Losartan inhibits the experimental venous thrombosis in spontaneously hypertensive rats. Thromb Res 1998; 90: 271-8.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Chabielska E., Pawlak R., WollnyT, Rólkowski R., Buczko W. Antithrombotic activity of losartan in two kidney, one clip hypertensive rats. A study on the mechanism of action. J Physiol Pharmacol 1999; 50: 99-109.[Medline]
[Order article via Infotrieve]
- Zatz R. A low-cost tail-cuff method for the estimation of mean arterial pressure in conscious rats. Lab Anim Sci 1990; 42:198-201.
- Reyers I., DeGaetano G., Donati MB Venostasis-induced thrombosis in rat is not influenced by circulating platelet or leukocyte number.AgentsActions 1989; 28: 137-40.
- Radomski MW, Palmer MJR, Moncada S.The role of nitric oxide and cGMP in platelet adhesion to vascular endothelium. Biochem Biophys Res Commun 1987; 148: 1482-89.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Pawlak R., Chabielska E., Golatowski J.,Azzadin A., Buczko W. Nitric oxide and prostacyclin are involved in antithrombotic action of captopril in venous thrombosis in rats. Thromb Haemost 1998; 79: 1208-12.[Web of Science][Medline]
[Order article via Infotrieve]
- Abramczyk P., Lisiecka A., Papierski K., Ziecina R., Przybylski J.Arterial hypertension due to occlusion of the adrenal vein in the rat is strain- dependent. J Hypertens 1998; 16: 1249-51.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Ploth DW Angiotensin-dependent renal mechanisms in two-kidney, one-clip renal vascular hypertension. Am J Physiol 1983; 245: F131-F141.[Web of Science][Medline]
[Order article via Infotrieve]
- MoriguchiA, Brosnihan KB, Kumagai H., Ganten D., Ferrario CM Mechanism of hypertension in transgenic rats expressing mouse Ren-2 gene. Am J Physiol 1994; 266: R1273-R1279.[Web of Science][Medline]
[Order article via Infotrieve]
- Handa RK Angiotensin-(1-7) can interact with the rat proximal tubule AT4 receptor system. Am J Physiol 1999; 277: F75-F83.[Web of Science][Medline]
[Order article via Infotrieve]
- Kerins DM, Hao Q., Vaughan DE Angiotensin induction of PAI-1 expression in endothelial cells is mediated by hexapeptide angiotensin IV. J Clin Invest 1995; 96: 2515-20.[Web of Science][Medline]
[Order article via Infotrieve]
- Provost P., Lam JYT, Lacoste L., Merhi Y., Waters D. Endothelium - derived nitric oxide attenuates neutrophil adhesion to endothelium under arterial flow conditions. Arterioscler Thromb 1994; 14: 331-5.[Abstract/Free Full Text]
- Crabos M., Bertschin S., Buhler FR et al. Identification of AT1-receptors on human platelets and decreased angiotensin II binding in hypertension.JHypertens 1993; 11: 5230-31.
- Moore TJ,Williams GH Angiotensin II receptors on human platelets. Circ Res 1982; 51: 314-20.[Abstract/Free Full Text]
- Campbell DJ, Menard J., Azizi M., Gonzales MF Synergistic interaction between angiotensin converting enzyme inhibition and angiotensin II antagonism in spontaneously hypertensive rats. J Hypertens 1997; 15(suppl): S63.[Web of Science]
- Li P., Ferrario CM, Brosnihan KB Losartan inhibits thromboxane A2-induced platelet aggregation and vascular constriction in spontaneously hypertensive rats. J Cardiovasc Pharmacol 1998; 32: 198-205.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Liu ECK, Hedberg A., Goldenberg HJ, Harris DN, Webb ML DuP 753, the selective angiotensin II blocker, is a competitive antagonist to human thromboxane A2/prostaglandin H2 (TP) receptors. Prostaglandins 1992; 44: 89-99.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Guera-Cuesta JI, Monton M., Rodriquez Feo JA et al. Effect of losartan on human platelet activation. J Hypertens 1999; 17: 447-52.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
Journal of Renin-Angiotensin-Aldosterone System, Vol. 1, No. 3,
268-272 (2000)
DOI: 10.3317/jraas.2000.041
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