Platelet Thromboxane A₂ Receptor Blockade by Losartan in Hypertensive Patients

Abstract

It has been shown that losartan inhibits vasoconstriction through binding to the thromboxane A₂ receptors. We investigated whether Thromboxane A₂-induced platelet aggregation can be inhibited by losartan and if this effect is present in losartan treated hypertensive patients. Platelet aggregation was measured in platelet rich plasma from healthy volunteers and hypertensive patients, with the use of an aggregometer. Losartan inhibited the effect of Thomboxane A₂ agonist (U46619)-induced platelet aggregation, with a pA₂ value of 48.9 μM and inhibited both second and first phases of Adenosine diphosphate-induced aggregation, from 109 ± 9 to 65 ± 10 mm and from 62± 8 to 0 mm. U46619's and Adenosine diphosphate's concentration required to produce half-maximal response were higher in normotensive volunteers (EC₅₀ 2.01 ± .3 μM and 2.6 ± .4 μM) compared to the hypertensive patients without treatment (EC₅₀ 0.6 ± .2 μM and 2.0 ± .3 μM). The concentration required to produce half-maximal response in losartan treated patients was similar to the healthy volunteers(EC₅₀ 1.7 ± .2 μM and 1.4 ± .3 μM), whereas in the lisinopril hypertension treated patients the concentrations used, were lower (EC₅₀ 1.4 ± .3 μM and 2.11 ± .5 μM). Losartan plasma concentration of hypertensive patients was 60.3 ± 18.7 ng/ml. Computer analysis showed that losartan, Thromboxane A₂ and the Thromboxane A₂ receptor antagonist, SQ29548 have equivalent functional groups and spatial distribution. Conclusion. We suggest that losartan inhibits platelet aggregation through Thromboxane A₂ dependent and independent mechanisms.

Key words: :

• Platelet aggregation
• TXA₂ receptors
• Losartan
• Angiotensin II

Notes

[8] Tallarida RJ, Murray RB. Manual of Pharmacological Calculations by Springer-Verlag new York Inc 1981.