Inhibition of platelet aggregability by losartan in essential hypertension

Most clinical events associated with hypertension have a thrombotic compone nt. Losartan is a selective, competitive antagonist of the thromboxane A(2) receptor in experiments performed in isolated vascular strips and in human and rat platelet-enriched plasma. In this study, we investigated for the f irst time whether losartan at therapeutic doses has an effect on platelet a ggregability and indexes of fibrinolysis in essential hypertensive subjects . Changes in the dose-response curve to platelet aggregation induced by the thrombin receptor-activating peptide SFLRRN-NH2 were determined in 9 patie nts (56% men, 72% white; mean age 52.8 years) with stage I or II essential hypertension and in 9 untreated healthy volunteers. After a 4-week washout period, hypertensive subjects received 2 weeks of placebo followed by 4 wee ks of losartan 50 mg/day. Both subjects and end points were blinded for tre atment assignment. In addition, plasminogen activator inhibitor type 1 anti gen and van Willebrand antigen were studied in all patients and controls. F our weeks of losartan produced a statistically significant (p <0.05) increa se in the concentration of SFLRRN-NH2 required to induce a half-maximal res ponse in platelet aggregation extent and rate 4 weeks after initiation of t reatment. The decrease in platelet aggregability was independent of blood p ressure control and the effects of gender and age. Losartan had no effect o n plasma concentrations of plasminogen activator inhibitor-1 and van Willeb rand factor in hypertensive subiects. These data demonstrate for the first time a novel antiplatelet effect of losartan at therapeutic doses, which wa s independent of changes in blood pressure, plasma markers of fibrinolytic activity, and endothelial perturbation. (C) 2000 by Excerpta Medica, Inc.