Possible Mechanisms for the Inhibitory Effect of Ruscus Extract on Increased Microvascular Permeability Induced by Histamine in Hamster Cheek Pouch

Extract of Ruscus aculeatus is used in treatment of venous insufficiency. In the present study, we used the hamster cheek pouch preparation and investigated in vivo the effects of an α1 and α2adrenoceptor antagonists, a calcium blocker, Ruscus extract, and their combination on increased microvascular permeability induced by histamine. Experiments were performed on male hamsters; 30 min after completion of the cheek pouch preparation, fluorescein-labeled dextran (molecular weight 150,000) was given intravenously (i.v.). Histamine, applied topically, increased the number of fluorescent vascular leakage sites from postcapillary venules, evidence of an increase in macromolecular permeability, which was quantified by ultraviolet light microscopy as the number of leaky sites in the prepared area. Prazosin (α1-adrenoceptor antagonist), diltiazem (calcium blocker), and Ruscus extract applied topically dosedependently inhibited the macromolecular permeability-increasing effect of histamine. Rauwolscine (α2-adrenoceptor antagonist), also applied topically, had no effect on histamine-induced permeability increase. Inhibition of the histamine-induced permeability increase evoked by Ruscus extract could be blocked by prazosin and by diltiazem but not by rauwolscine. These results indicate that any variation in the transmembrane flux of calcium impairs formation of microvascular leaky sites by histamine. Our results show that Ruscus extract has a protective effect against the leakage of FITC-dextran in hamster cheek pouch after administration of histamine that is modulated by calcium and selectively by α1-adrenoceptors.