Losartan inhibits in vitro platelet activation: comparison with candesartan and valsartan.
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.
Núñez
A
A
Cardiovascular Research and Hypertension Laboratory, Fundacion Jimenez Diaz, Madrid, 28040, Spain.
Gómez
J
J
Zalba
L R
LR
Montón
M
M
Jiménez
A
A
Velasco
S
S
López-Blaya
A
A
Uriarte
A C
AC
Casado
S
S
López-Farré
A
A
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
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