Study of the mechanisms involved in adenosine-5′-O-(2-thiodiphosphate) induced relaxation of rat thoracic aorta and pancreatic vascular bed

摘要

1. The endothelium-dependent relaxation of blood vessels induced by P_(2Y)-purinoceptor activation has often been shown to involve prostacyclin and/or nitric oxide (NO) release. In this work, we have investigated the mechanisms involved in the relaxant effect of the P_(2Y) agonist, adenosine -5′-O-(2-thiodiphosphate) (ADPβS) using two complementary preparations: rat pancreatic vascular bed and aortic ring. 2. On the pancreatic vascular bed, ADPβS (1.5 and 15 μM) infused for 30 min induced a concentration-dependent vasodilatation; it was progressive during the first 10 min (first period) and sustained from 10 to 30 min (second period). Indomethacin (10 μM) delayed ADPβS-induced vasodilatation (1.5 and 15 μM) by about 6 min. N~ω-nitro-L-arginine methyl ester (L-NAME) (200 μM) suppressed the relaxation for about 5 min but thereafter ADPβS at the two concentrations progressively induced an increase in the flow rate. Even the co-administration of L-NAME and indomethacin did not abolish the ADPβS-induced vasorelaxation. 3. On 5-hydroxy tryptamine (5-HT) precontracted rings mounted in isometric conditions in organ baths, we observed that ADPβS induced a concentration-dependent relaxation of rings with a functional endothelium; this effect was stable for 25 min. The ADPβS relaxant effect was strongly inhibited by Reactive Blue 2 (30 μM) and was suppressed by pretreatment of rings with saponin (0.05 mg ml~(-1) for 30 min), which also abolished the acetylcholine-induced relaxation. 4. ADPβS-induced relaxation of 5-HT precontracted rings is largely inhibited by indomethacin (100 or 10 μM) or L-NAME (100 μM). 5. We conclude that: the ADPβS-induced relaxation is endothelium-dependent, mediated by P_(2Y)-purinoceptors, and at least in part linked to NO and prostacyclin release, depending on the preparation used. Furthermore, on the pancreatic vascular bed, (an)other mechanism(s) than prostacyclin and NO releases may be involved in ADPβS-induced vasodilatation.