Endothelin-3-Induced Relaxation of Isolated Rat Basilar Artery is Mediated by an Endothelial ETB-Type Endothelin Receptor

Abstract

The endothelin (ET) receptor mediating relaxation of cerebral arteries was characterized using ring segments obtained from the rat basilar artery. Under resting tension, ET-3 (>10−8 M) but not the specific ETB receptor agonist IRL 1620 induced contraction. In ring segments precontracted with 3 × 10−6 M prostaglandin (PG) F2α, ET-3 (10−12–10−8 M) and IRL 1620 (10−14–10−6 M) induced concentration-related relaxation. IRL 1620 was more potent than ET-3, the pD2 (-log10EC50) values being 10.002 ± 0.751 (mean ± SD) for IRL 1620 and 8.836 ± 0.415 for ET-3. Relaxation was abolished after preincubation with the nitric oxide (NO) synthase inhibitor NG-nitro-l-arginine (10−5 M) as well as in segments devoid of a functionally intact endothelium. At a concentration above 10−8 M, ET-3 resulted in a further increase of PGF2α-induced contraction that was not observed with IRL 1620. The presumably specific ETB receptor antagonist IRL 1038 (10−7–3 × 10−6 M) diminished or even abolished (3 × 10−6 M) the relaxation induced by ET-3 or IRL 1620. IRL 1038 did not exert any vasomotor effect by itself, and it did not significantly affect ET-3-induced contraction. These results indicate that in the rat isolated basilar artery, the ET-3-induced relaxation is probably due to activation of an ETB-type receptor located on the endothelial cells and mediated by release of nitric oxide.