ENDOTHELIN-3-INDUCED RELAXATION OF ISOLATED RAT BASILAR ARTERY IS MEDIATED BY AN ENDOTHELIAL ET(B)-TYPE ENDOTHELIN RECEPTOR

The endothelin (ET) receptor mediating relaxation of cerebral arteries was characterized using ring segments obtained from the rat basilar a rtery. Under resting tension, ET-3 (>10(-8) M) but not the specific ET (B) receptor agonist IRL 1620 induced contraction. In ring segments pr econtracted with 3 x 10(-6) M prostaglandin (PG) F-2 alpha, ET-3 (10(- 12)-10(-8) M) and IRL 1620 (10(-14)-10(-6) M) induced concentration-re lated relaxation. IRL 1620 was more potent than ET-3, the pD(2) (-log( 10)EC(50)) values being 10.002 +/- 0.751 (mean +/- SD) for IRL 1620 an d 8.836 +/- 0.415 for ET-3. Relaxation was abolished after preincubati on with the nitric oxide (NO) synthase inhibitor N-G-nitro-L-arginine (10(-5) M) as well as in segments devoid of a functionally intact endo thelium. At a concentration above 10(-8) M, ET-3 resulted in a further increase of PGF(2 alpha)-induced contraction that was not observed wi th IRL 1620. The presumably specific ET(B) receptor antagonist IRL 103 8 (10(-7)-3 x 10(-6) M) diminished or even abolished (3 x 10(-6) M) th e relaxation induced by ET-3 or IRL 1620. IRL 1038 did not exert any v asomotor effect by itself, and it did not significantly affect ET3-ind uced contraction. These results indicate that in the rat isolated basi lar artery, the ET3-induced relaxation is probably due to activation o f an ET(B)-type receptor located on the endothelial cells and mediated by release of nitric oxide.