Nephrol Dial Transplant (2001) 16: 45-49
© 2001 European Renal Association-European Dialysis and Transplant Association
Angiotensin II AT1 receptor antagonists and platelet activation
Fundación Jiménez Díaz, Cardiovascular Research and Hypertension Laboratory, Avda Reyes Católicos 2, 28040 Madrid, Spain
Multiple factors are involved in thrombus formation and require complex and highly therapeutic strategies. Platelet activation plays a critical role in the genesis of acute coronary syndromes involving not only platelets but also endothelial cells, leucocytes and erythrocytes. Angiotensin II (Ang II) is a vasoconstrictor that could participate in the thrombotic process. Platelets also express Ang II AT1 type receptors on their surface. Losartan is a non-peptidic inhibitor of AT1 receptors. It has been demonstrated that losartan reduced platelet aggregation induced by the thromboxane A2 (TXA2) analogue U46619. This effect was not observed with the losartan metabolite EXP 3174. The effect of losartan was assessed in binding studies in which losartan competitively inhibited the binding of [3H]U46619 to platelets in a dose-dependent manner. Irbesartan also inhibits the TXA2 receptor in platelets, an effect that was not obtained with the active form of candesartan, CV11974, and with valsartan. These results suggest that the structural requirements necessary to antagonize the TXA2/PGH2 platelet receptor may be different from those involved in AT1 receptor antagonism. The in vivo relevance of the in vitro findings has been confirmed by the fact that in vivo administration of losartan decreases P-selectin expression in platelets obtained from stroke-prone spontaneously hypertensive rats.
Keywords: angiotensin; AT1 receptors; platelets; thromboxane A2; thrombus
Correspondence and offprint requests to: Dr Antonio López Farré, Cardiovascular Research and Hypertension Laboratory, Fundación Jiménez Díaz, Avda. Reyes Católicos 2, Madrid. 28040, Spain.
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