STUDY OF THE MECHANISMS INVOLVED IN ADENOSINE-5'-O-(2-THIODIPHOSPHATE) INDUCED RELAXATION OF RAT THORACIC AORTA AND PANCREATIC VASCULAR BED

1 The endothelium-dependent relaxation of blood vessels induced by P-2 Y-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, ad enosine -5'-O-(2-thiodiphosphate) (ADP beta S) using two complementary preparations: rat pancreatic vascular bed and aortic ring. 2 On the p ancreatic vascular bed, ADP beta S (1.5 and 15 mu M) infused for 30 mi n induced a concentration-dependent vasodilatation; it was progressive during the first 10 min (first period) and sustained from 10 to 30 mi n (second period). Indomerhacin (10 mu M) delayed ADP beta S-induced v asodilatation (1.5 and 15 mu M) by about 6 min. N-omega-nitro-L-argini ne methyl ester (L-NAME) (200 mu M) suppressed the relaxation for abou t 5 min but thereafter-ADP beta S at the two concentrations progressiv ely induced an increase in the flow rate. Even the co-administration o f L-NAME and indomethacin did not abolish the ADP beta S-induced vasor elaxation. 3 On 5-hydroxy tryptamine (5-HT) precontracted rings mounte d in isometric conditions in organ baths, we observed that ADP beta S induced a concentration-dependent relaxation of rings with a functiona l endothelium; this effect was stable for 25 min. The ADP beta S relax ant effect was strongly inhibited by Reactive Blue 2 (30 mu M) 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 ADP beta S-induced relaxation of 5-HT precontracted rings is largely i nhibited by indomethacin (100 or 10 mu M) or L-NAME (100 mu M). 5 We c onclude that: the ADP beta S-induced relaxation is endothelium-depende nt, mediated by P-2Y-purinoceptors, and at least in part linked to NO and prostacyclin release, depending on the preparation used. Furthermo re, on the pancreatic vascular bed, (an)other mechanism(s) than prosta cyclin and NO releases may be involved in ADP beta S-induced vasodilat ation.