Inhibition of platelet activation in stroke-prone spontaneously hypertensive rats: comparison of losartan, candesartan, and valsartan.

Abstract

In vitro studies have suggested that losartan interacts with the thromboxane (TxA2)/ prostaglandin H2 (PGH2) receptor in human platelets, reducing TxA2-dependent platelet activation. The aim of this study was to evaluate the effect of different angiotensin II type 1 receptor antagonists in stroke-prone spontaneously hypertensive rats (SHRSP). The level of platelet activation was assessed by determining P-selectin expression in platelets by flow cytometry. The ex vivo adhesion of platelets was also analyzed. The number of platelets that expressed P-selectin in SPSHR was significantly increased (% P-selectin expression: WKY 4 +/- 0, 4%; SHRSP 15.5 +/- 0, 8% [n = 8], p < 0.05). In SHRSP receiving losartan (20 mg/kg body weight per day) the percentage of platelets expressing P-selectin fell to levels close to that observed in WKY. The number of platelets from SHRSP treated with valsartan and candesartan (20 mg/kg body weight per day for 14 days) that expressed P-selectin was not significantly different from those from untreated SPRHR. Only losartan treatment reduced ex vivo platelet adhesion to a synthetic surface. The antiplatelet effect of losartan does not appear to be related to the level of blood pressure reduction. In ex vivo experiments, losartan significantly reduced the binding of the radiolabeled TxA2 agonist U46619 to platelets obtained from SHRSP in a dose-dependent manner. Treatment with losartan reduced the number of activated platelets in SHRSP independently of its blood pressure effects. TxA2-receptor blockade is proposed as a mechanism by which losartan can prevent platelet activation.

• Authors: A M Jiménez, M Montón, R García, A Núñez, J Gómez, L Rico, E García-Colis, L S de Miguel, M M Arriero, F Cabestrero, J Farré, S Casado, A López-Farré
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 37 Issue 4 Pg. 406-12 (Apr 2001) ISSN: 0160-2446 [Print] United States
• PMID: 11300653 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antihypertensive Agents
• Benzimidazoles
• Biphenyl Compounds
• P-Selectin
• Tetrazoles
• Thromboxane A2
• 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
• Valsartan
• Valine
• Losartan
• candesartan

Topics

• 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid (metabolism)
• Animals
• Antihypertensive Agents (pharmacology)
• Benzimidazoles (pharmacology)
• Biphenyl Compounds
• Blood Platelets (drug effects, metabolism, physiology)
• Blood Pressure
• Humans
• Hypertension (blood, physiopathology)
• Losartan (pharmacology)
• P-Selectin (genetics, metabolism)
• Platelet Activation (drug effects, physiology)
• Platelet Adhesiveness
• Rats
• Rats, Inbred SHR
• Rats, Inbred WKY
• Stroke (physiopathology)
• Tetrazoles (pharmacology)
• Thromboxane A2 (metabolism)
• Valine (analogs & derivatives, pharmacology)
• Valsartan