Endothelin-3-induced relaxation of isolated rat basilar artery is mediated by an endothelial ETB-type endothelin receptor.
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 x 10(-6) M prostaglandin (PG) F2 alpha, 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 PGF2 alpha-induced contraction that was not observed with IRL 1620. The presumably specific ETB receptor antagonist IRL 1038 (10(-7) - 3 x 10(-6) M) diminished or even abolished (3 x 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.
Schilling
L
L
Department of Physiology, University of Munich, Germany.
Feger
G I
GI
Ehrenreich
H
H
Wahl
M
M
D000109:Acetylcholine / Q000494:pharmacology; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001488:Basilar Artery / Q000502:physiology; D016232:Endothelins / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D051381:Rats; D017208:Rats, Wistar; D017466:Receptors, Endothelin / Q000502:physiology*
D016232:Endothelins; D017466:Receptors, Endothelin; D019335:Nitroarginine; D009569:Nitric Oxide; D006632:Histamine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D000109:Acetylcholine