Crataegus Special Extract WS 1442 Causes Endothelium-dependent Relaxation via a Redox-sensitive Src- and Akt-dependent Activation of Endothelial NO Synthase but Not via Activation of Estrogen Receptors

Purpose: This study determined whether the Crataegus (Hawthorn species) special extract WS (R) 1442 stimulates the endothelial formation of nitric oxide (NO), a vasoprotective factor, and characterized the Underlying, mechanism. Methods and Results: Vascular reactivity was assessed in porcine coronary artery rings, reactive oxygen species (ROS) formation in artery sections by microscopy, and phosphorylation of Akt and endothelial NO synthase (eNOS) in endothelial cells by Western blot analysis. WS (R) 1442 caused endothelium-dependent relaxations in coronary, artery rings, which were reduced by N-omega-nitro-L-arginine (it competitive inhibitor of NO synthase) and by charybdotoxin plus apamin (two inhibitors of endothelium-derived hyperpolarizing factor-mediated responses). Relaxations to WS (R) 1442 were inhibited by intracellular ROS scavengers and inhibitors of Src and P13-kinase, but not by an estrogen receptor antagonist. WS (R) 1442 stimulated the endothelial formation of ROS in artery sections, and a redox-sensitive phosphorylation of Akt and eNOS in endothelial cells. Conclusions: WS (R) 1442 induced endothelium-dependent NO-mediated relaxations of coronary artery rings through the redoxsensitive Src/P13-kinase/Akt-dependent phosphorylation of eNOS.