Interactions of Ruscus-extract with endothelin-receptors in human varicose veins

Extract of the plant Ruscus aculeatus is used in the treatment of venous insufficiency. Endothelins represent a family of vasoconstrictor peptides produced by vascular endothelial cells. In animals, venous smooth muscle is more sensitive to the vasoconstrictor action of endothelin-1 than arterial smooth muscle. Experiments were designed to determine whether or not contractions of human varicose veins to Ruscus require activation of endothelin-receptors. Rings cut from greater saphenous veins and varicose tributaries of patients (3 male, 17 females) undergoing vein stripping for primary varicosity were suspended in organ chambers for the measurement of isometric force. The endothelium was mechanically removed from some rings. Ruscus-extract caused concentration-dependent contractions which were greater in varicose tributaries than in greater saphenous veins; contractions were similar in rings with and without endothelium in each type of vein. Phentolamine and propranolol, to block alpha- and beta-adrenergic receptors, respectively, significantly reduced maximal tensions developed to the extract in each type of vein. BQ-123 (10^-6 M) which blocks selectively endothelin- A receptors did not reduce contractions to Ruscus in segments of human greater saphenous or varicose veins without endothelium. On the contrary, in the presence of BQ-123 contractions of varicose veins with endothelium were increased. These results suggest that in vitro, Ruscus-extract causes concentration-dependent contractions in leg veins of patients with primary varicosity; varicose tributaries are more sensitive to the contractile effects of Ruscus-extract than segments of greater saphenous veins from the same patient. Contractions to Ruscus are independent of the endothelium and mediated by activation of adrenergic but not endothelin-A receptors on the smooth muscle.