Analysis of rabbit vascular responses to DBI, an ingol derivative isolated from Euphorbia canariensis

We have analysed the effects of 7,12-O-diacetyl-8-O-benzoil-2,3-diepiingol (DBI), an ingol derivative isolated from E. canariensis, on isometric tension developed by isolated rabbit basilar and carotid arteries. Concentration-response curves to DBI (10(-8)-3 x 10(-5) M) were obtained cumulatively in both arteries at resting tension and active tone (KCl, 50 mM). At resting tension, DBI induced a concentration-dependent contraction, which was not inhibited in Ca2+-free medium. H7 (1-(5-isoquinoline sulphonyl)-2-methylpiperazine dichloride) (10(-4) M) inhibited the DBI-induced contraction both in basilar and in carotid arteries. Calmidazolium (10(-4) M) inhibited the maximum contraction of the carotid artery to DBI, and completely abolished the response in the basilar artery. In pre-contracted basilar arteries DBI induced a concentration-dependent relaxation that was not modified by incubation with N-G-nitro-L-arginine (L-NOARG; 10(-5) M) or indomethacin (10(-5) M). In the carotid artery with active rone DBI induced further contractions, which were not significantly modified by L-NOARG (10(-5) M) and were potentiated by indomethacin (10(-5) M). These results suggest that DBI contracts rabbit basilar and carotid arteries by a mechanism that is independent of extracellular Ca2+ and involves the participation both of protein kinase C and of calmodulin. DBI relaxes basilar but not carotid arteries by a mechanism independent of the liberation of nitric oxide and prostacyclin. In the carotid artery prostacyclin but not nitric oxide partially counteracts the contractile action of DBI.