|
Sign In to gain access to subscriptions and/or personal tools.
|
Losartan inhibits in vitro platelet activation: comparison with candesartan and valsartan
Antonio Núñez
Cardiovascular Research and Hypertension Laboratory, Fundación Jiménez Díaz, Madrid, Spain
Juan Gómez
Cardiovascular Research and Hypertension Laboratory, Fundación Jiménez Díaz, Madrid, Spain
Luis Rico Zalba
Cardiovascular Research and Hypertension Laboratory, Fundación Jiménez Díaz, Madrid, Spain
Mercedes Montón
Cardiovascular Research and Hypertension Laboratory, Fundación Jiménez Díaz, Madrid, Spain
Ana Jiménez
Cardiovascular Research and Hypertension Laboratory, Fundación Jiménez Díaz, Madrid, Spain
Sandra Velasco
Cardiovascular Research and Hypertension Laboratory, Fundación Jiménez Díaz, Madrid, Spain
Almudena López-Blaya
Cardiovascular Research and Hypertension Laboratory, Fundación Jiménez Díaz, Madrid, Spain
Angel Celdrán Uriarte
Cardiovascular Research and Hypertension Laboratory, Fundación Jiménez Díaz, Madrid, Spain
Santos Casado
Cardiovascular Research and Hypertension Laboratory, Fundación Jiménez Díaz, Madrid, Spain
Antonio López-Farré
Cardiovascular Research and Hypertension Laboratory, Fundación Jiménez Díaz, Madrid, Spain, alopeza{at}fjd.es
A recent study has shown that losartan, an AT1-receptor antagonist, interacts with thromboxane A2 (TxA2)/prostaglandin H2 (PGH2) receptors in human platelets. The aim of the present study was to analyse the ability of different angiotensin II (Ang II) AT1-receptor antagonists to inhibit TxA2-dependent human platelet activation. Platelets were obtained from healthy volunteers and were stimulated with the thromboxane A2 analogue, U46619 (10-6 mol/L). U46619-stimulated platelet activation was significantly reduced by losartan in a dose-dependent manner. Only maximal doses of valsartan (5x10-6 mol/L), reduced U46619-induced platelet activation. The active form of candesartan cilexetil, candesartan (CV-11974), failed to modify platelet activation. Losartan reduced the binding of [3H]-U46619 to platelets, an effect that was observed to a lesser extent with valsartan but not with CV-11974. These results suggest that, whilst some AT1-receptor antagonists reduce TxA2-dependent human platelet activation, it is not a feature common to all AT1 antagonists.
Key Words: platelets • AT1 antagonists • receptors • thromboxane A2
References
- Furukawa Y., Kishimoto S., Nishikawa K. Hypotensive imidazole-5-acetic acid derivatives. US patent 4, 355,040. Issued to Takeda Chemical Industries LTD (Osaka, Japan), 1982.
- Wong PC, Price WA Jr, Chiu AT et al. Nonpeptide angiotensin II receptor antagonist: studies with EXP9270 and DuP753. Hypertension 1990; 15:823-34.[Abstract/Free Full Text]
- Siegl PKS. Discovery of losartan, the first specific non-peptide angiotensin II receptor antagonist. J Hypertension 1993; 11:S19-S22.[Web of Science]
- Burrell LM, Johnston CI Angiotensin II receptor antagonists check ref.potential in elderly patients with cardiovascular disease. Drugs & Aging 1997; 10:421-34.[Web of Science][Medline]
[Order article via Infotrieve]
- Patrono C., Renda G. Platelet activation and inhibiton in unstable coronary syndromes. Am J Cardiol 1997; 80:17E-20E.[CrossRef][Medline]
[Order article via Infotrieve]
- Li P., Ferrario CM, Brosnihan KB Nonpeptide angiotensin II antagonist losartan inhibits thromboxane A2-induced contractions in canine coronary arteries.JPharmacol Exp Ther 1997; 281:1065-70.[Abstract/Free Full Text]
- Bertolino F., Valentín JP, Maffre M., Jover B., Bessac AM, John GW Prevention of thromboxane A2 receptor-mediated pulmonary hypertension by a nonpeptide angiotenin II type 1 receptor antagonist. J Pharmacol Exp Ther 1994; 268:747-52.[Abstract/Free Full Text]
- Guerra JI, Montón M., Rodríguez-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]
- López-Farré A., Caramelo C., Esteban A. et al. Effects of aspirin on platelet-neutrophil interactions. Role of nitric oxide and endothelin-1. Circulation 1995; 91:2080-8.[Abstract/Free Full Text]
- López-Farré A., Riesco A., Digiuni E. et al.Aspirin-stimulated nitric oxide production by neutrophils after acute myocardial ischemia in rabbits. Circulation 1996; 94:83-7.[Abstract/Free Full Text]
- Kattelman EJ, Venton DL, Le Breton GC Characterization of U46619 binding in unactivated intact human platelets and determinations of binding site affinities of four TxA2/PGH2 receptor antagonists. Thromb Res 1986; 41:471-81.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Corriu C., Bernard S., Schott C., Stoclet JC Effects of losartan on cantractile responses of conductance and resistance arteries from rats. J Cardiovasc Pharmacol 1995; 26:688-92.[Web of Science][Medline]
[Order article via Infotrieve]
- Kroll MH, SchaferAL Biochemical mechanisms of platelet activation. Blood 1989; 74:1181-90.[Free Full Text]
- Marcus AJ, Safier LB Thromboregulation: multicellular modulation of platelet reactivity in haemostasis and thrombosis. FASEB J 1995; 91:2080-8.
- Moncada S., Palmer RMJ, Higgs EA Nitric oxide: physiology, pathophysiology. Pharmacol Rev 1991; 43:109-41.[Web of Science][Medline]
[Order article via Infotrieve]
- Gohlke P., Pees C., Unger T. AT2 stimulation increases aortic cyclic GMPc in SHRSP by a kinin-dependent mechanism. Hypertension 1998; 31:349-55.[Abstract/Free Full Text]
- Ridker PM, Gaboury CL, Conlin PR, Seely EW,Williams GH, Vaughan DE Stimulation of plasminogen activator inhibitor in vivo by infusion of angiotensin II. Evidence of a potential interaction between the renin-angiotensin system and fibrinolytic function. Circulation 1993; 87:1969-73.[Abstract/Free Full Text]
- Timmermans Pbmwm, Smith RDAngiotensin II receptor subtypes: selective antagonists and functional correlates. Eur Heart J1994; 15:79-87.
Journal of Renin-Angiotensin-Aldosterone System, Vol. 1, No. 2,
175-179 (2000)
DOI: 10.3317/jraas.2000.022
 CiteULike  Complore  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter What's this?
|
|
