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 (KCI, 50 mM). At resting tension, DBI induced a concentration-dependent contraction, which was not inhibited in Ca(2+)-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 NG-nitro-L-arginine (L-NOARG; 10(-5) M) or indomethacin (10(-5) M). In the carotid artery with active tone 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.
Miranda
F J
FJ
Department of Physiology, University of Valencia, Spain.
Alabadí
J A
JA
Pérez
P
P
Ortí
M
M
Centeno
J M
JM
Yuste
A
A
Sanz-Cervera
J F
JF
Marco
J A
JA
Alborch
E
E
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D017536:Carotid Artery, Common / Q000187:drug effects / Q000378:metabolism; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000378:metabolism; D007840:Latex / Q000737:chemistry; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry; D011493:Protein Kinase C / Q000378:metabolism; D011817:Rabbits
C107498:7,12-O-diacetyl-8-O-benzoyl-2,3-di(epi)ingol; D002147:Calmodulin; D004224:Diterpenes; D004791:Enzyme Inhibitors; D007840:Latex; D010936:Plant Extracts; D019335:Nitroarginine; D009569:Nitric Oxide; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011464:Epoprostenol; D011493:Protein Kinase C; D002118:Calcium