Comparative analysis of the vascular actions of diterpenes isolated from Euphorbia canariensis

Abstract

We have analysed the effects of 2,3-diepiingol 7,12-diacetate-8-isobutyrate (compound 1), ingenol-3-angelate-17-benzoate (compound 2), ingenol-3-angelate-17-benzoate-20-acetate (compound 3) and 3,5,7,8,9,15-hexahydroxyjatropha-6(17),11-dien-14-one-5,8-bis(2-methylbutyrate) -7-(2-methylpropionate) (compound 4), four diterpenes isolated from E. canariensis, on the isometric tension developed by isolated rabbit basilar and carotid arteries. Concentration-response curves to these compounds were obtained cumulatively in both arteries at resting tension and active tone (KCl, 50 mM). At resting tension a concentration-dependent contraction was induced by the four compounds. In the basilar artery the order of potency was 3 = 1 > 2 = 4, without significant differences between E(max) values. In the carotid artery the order of potency was 3 > 2 = 1 = 4 and there were no significant differences between the E(max) (maximum effect) values of compounds 1-3, all of which were higher than that of compound 4. In pre-contracted basilar artery compounds 1-3 induced concentration-dependent relaxation and compound 4 was almost ineffective; the order of potency was 3 > 2 = 1 without significant differences between E(max) values. In the carotid artery with active tone the four compounds tested induced further contractions; the order of potency was 3 > 2 = 4 > 1 without significant differences between E(max) values. These results show that the four diterpenes are potent active substances in rabbit basilar and carotid arteries and that there are regional differences between their action. The four compounds tested contract basilar and carotid arteries at resting tension. Compounds 1-3 relax pre-contracted basilar artery but not carotid artery.