title: Role of endothelin receptors, calcium and nitric oxide in the potentiation by endothelin-1 of the sympathetic contraction of rabbit ear artery during cooling.
abstract: 1. To examine further the potentiation by endothelin-1 on the vascular response to sympathetic stimulation, we studied the isometric response of isolated segments, 2 mm long, from the rabbit central ear artery to electrical field stimulation (1-8 Hz), under different conditions, at 37 degrees C and during cooling (30 degrees C). 2. Electrical stimulation produced frequency-dependent contraction, which was reduced (about 63% for 8 Hz) during cooling. At 30 degrees C, but not at 37 degrees C, endothelin-1 (1, 3 and 10 nM) potentiated the contraction to electrical stimulation in a dose-dependent way (from 43 +/- 7% to 190 +/- 25% for 8 Hz). 3. This potentiation by endothelin-1 was reduced by the antagonist for endothelin ETA receptors BQ-123 (10 microM) but not by the antagonist for endothelin ETB receptors BQ-788 (10 microM). The agonist for endothelin ETB receptors IRL-1620 (0.1 microM) did not modify the contraction to electrical stimulation. 4. The blocker of L-type Ca2+ channels verapamil (10 microM l-1) reduced (about 72% for 8 Hz) and the unspecific blocker of Ca(2+)-channels NiCl2 (1 mM) practically abolished (about 98%), the potentiating effects of endothelin-1 found at 30 degrees C. 5. Inhibition of nitric oxide synthesis with NG-nitro-L-arginine (L-NOARG, 0.1 mM) increased the contraction to electrical stimulation at 30 degrees C more than at 37 degrees C (for 8 Hz, this increment was 297 +/- 118% at 30 degrees C, and 66 +/- 15% at 37 degrees C). Endothelium removal increased the contraction to electrical stimulation at 30 degrees C (about 91% for 8 Hz) but not at 37 degrees C. Both L-NOARG and endothelium removal abolished the potentiating effects of endothelin-1 on the response to electrical stimulation found at 30 degrees C. 6. These results in the rabbit ear artery suggest that during cooling, endothelin-1 potentiates the contraction to sympathetic stimulation, which could be mediated at least in part by increasing Ca2+ entry after activation of endothelin ETA receptors. This potentiating effect of endothelin-1 may require the presence of an inhibitory tone due to endothelial nitric oxide.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma, Madrid, Spain.
authors.forename: A L
authors.initials: AL
authors.lastname: García-Villalón
authors.forename: J
authors.initials: J
authors.lastname: Padilla
authors.forename: N
authors.initials: N
authors.lastname: Fernández
authors.forename: L
authors.initials: L
authors.lastname: Monge
authors.forename: B
authors.initials: B
authors.lastname: Gómez
authors.forename: G
authors.initials: G
authors.lastname: Diéguez
mesh_terms: D000818:Animals; D001158:Arteries / Q000294:innervation; D002118:Calcium / Q000502:physiology*; D003080:Cold Temperature; D004423:Ear / Q000098:blood supply; D004558:Electric Stimulation; D019332:Endothelin-1 / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine / Q000494:pharmacology; D011817:Rabbits; D017466:Receptors, Endothelin / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D019332:Endothelin-1; D017466:Receptors, Endothelin; D019335:Nitroarginine; D009569:Nitric Oxide; D002118:Calcium