title: Losartan inhibits in vitro platelet activation: comparison with candesartan and valsartan.
abstract: A recent study has shown that losartan, an AT(1)-receptor antagonist, interacts with thromboxane A(2) (TxA(2))/prostaglandin H(2) (PGH(2)) receptors in human platelets. The aim of the present study was to analyse the ability of different angiotensin II (Ang II) AT(1)-receptor antagonists to inhibit TxA(2)-dependent human platelet activation. Platelets were obtained from healthy volunteers and were stimulated with the thromboxane A(2) 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 [(3)H]-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 AT(1)-receptor antagonists reduce TxA(2)-dependent human platelet activation, it is not a feature common to all AT(1) antagonists.
authors.affiliation: Cardiovascular Research and Hypertension Laboratory, Fundacion Jimenez Diaz, Madrid, 28040, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Núñez
authors.forename: J
authors.initials: J
authors.lastname: Gómez
authors.forename: L R
authors.initials: LR
authors.lastname: Zalba
authors.forename: M
authors.initials: M
authors.lastname: Montón
authors.forename: A
authors.initials: A
authors.lastname: Jiménez
authors.forename: S
authors.initials: S
authors.lastname: Velasco
authors.forename: A
authors.initials: A
authors.lastname: López-Blaya
authors.forename: A C
authors.initials: AC
authors.lastname: Uriarte
authors.forename: S
authors.initials: S
authors.lastname: Casado
authors.forename: A
authors.initials: A
authors.lastname: López-Farré
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004347:Drug Interactions; D006801:Humans; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000068756:Valsartan
chemical_list: D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D010975:Platelet Aggregation Inhibitors; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D000068756:Valsartan; D014633:Valine; D019808:Losartan; C081643:candesartan