Cistus ladaniferus L. (Cistaceae) is a medicinal plant originated from the Mediterranean region which exerts different pharmacological effects. In the present study, our goal was to examine whether the plant possessed antihypertensive properties. Aqueous extract of Cistus leaves (AEC, 500 mg/kg/day) reduced systemic blood pressure (SBP) in two animal models of hypertension, the L-NAME and renovascular two kidney-one clip (2K-1C) hypertensive rats. In the former, AEC prevented the increase in SBP when co-administered with L-NAME during four weeks (164 +/- 3 mm Hg in L-NAME vs. 146 +/- 1 mm Hg in L-NAME + AEC, p < 0.001). In the latter, AEC reversed the increase in SBP when administered during four weeks after installation of the hypertension (146 +/- 5 mm Hg with AEC vs. 179 +/- 6 mm Hg without, p < 0.05). AEC treatment also reversed the endothelial dysfunction observed in both animal models of hypertension. A direct effect on cardiac and vascular tissue was also tested by examining the contractile effects of AEC in rat isolated aortic rings and Langendorff perfused hearts. AEC (10 mg/L) had no effect on left ventricular developed pressure and heart rate in isolated perfused heart. However, AEC produced a strong relaxation of pre-contracted rat aortic rings (80 +/- 2% relaxation, n = 25). When the rings were denuded from endothelium or were incubated with 1 mM N omega-nitro-L-arginine (L-NNA), the relaxant effect of AEC was lost. We conclude that C. ladaniferus possesses antihypertensive properties which are mainly due to an endothelium-dependent vasodilatory action. (C) 2009 Elsevier Inc. All rights reserved.