Angiotensin II AT(1) receptor antagonists and platelet activation
| Autor: | Antonio Núñez, Lourdes Sánchez de Miguel, Ana Jiménez, Juan Gómez, Antonio López-Farré, Almudena Lopez‐Bloya, M Montón, L. Rico, Santos Casado |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
medicine.medical_specialty
Platelet Aggregation Thromboxane Receptors Thromboxane Tetrazoles Coronary Disease Receptor Angiotensin Type 2 Losartan Receptor Angiotensin Type 1 Thromboxane A2 chemistry.chemical_compound Angiotensin Receptor Antagonists Internal medicine Rats Inbred SHR medicine Animals Humans Platelet Platelet activation Antihypertensive Agents Transplantation Angiotensin II receptor type 1 business.industry Coronary Thrombosis Biphenyl Compounds Thrombosis Valine Platelet Activation Angiotensin II Rats P-Selectin Endocrinology chemistry Nephrology 15-Hydroxy-11 alpha 9 alpha-(epoxymethano)prosta-5 13-dienoic Acid cardiovascular system Valsartan Benzimidazoles business hormones hormone substitutes and hormone antagonists circulatory and respiratory physiology medicine.drug |
| Zdroj: | Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 16 |
| ISSN: | 0931-0509 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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