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 insufficien cy. In the present study, we used the hamster cheek pouch preparation and investigated in vivo the effects of an alpha(1) and alpha(2)adreno ceptor antagonists, a calcium blocker, Ruscus extract, and their combi nation on increased microvascular permeability induced by histamine. E xperiments were performed on male hamsters; 30 min after completion of the cheek pouch preparation, fluorescein-labeled dextran (molecular w eight 150,000) was given intravenously (i.v.). Histamine, applied topi cally, increased the number of fluorescent vascular leakage sites from postcapillary venules, evidence of an increase in macromolecular perm eability, which was quantified by ultraviolet light microscopy as the number of leaky sites in the prepared area. Prazosin (alpha(1)-adrenoc eptor antagonist), diltiazem (calcium blocker), and Ruscus extract app lied topically dosedependently inhibited the macromolecular permeabili ty-increasing effect of histamine. Rauwolscine (alpha(2)-adrenoceptor antagonist), also applied topically, had no effect on histamine-induce d permeability increase. Inhibition of the histamine-induced permeabil ity 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 mi crovascular leaky sites by histamine. Our results show that Ruscus ext ract has a protective effect against the leakage of FITC-dextran in ha mster cheek pouch after administration of histamine that is modulated by calcium and selectively by alpha(1)-adrenoceptors. -