title: Contribution of α-adrenoceptor stimulation by phenylephrine to basal nitric oxide production in the isolated mouse aorta.
abstract: In the mouse aorta, contractions evoked by the α(1)-adrenoceptor agonist phenylephrine are strongly suppressed by the continuous production of nitric oxide (NO). We investigated whether phenylephrine itself stimulated NO production by activating endothelial α(2)-adrenoceptors. On a prostaglandin F(2α) contraction, the α(2)-adrenoceptor agonist 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK14304) induced 29.3 ± 7.4% relaxation, which was inhibited by 0.1 μM 2-[(4,5-Dihydro-1H-imidazol-2-yl)methyl]-2,3-dihydro-1-methyl-1H-isoindole (BRL44408) with a pKB' corresponding to α(2)-antagonism. In the presence of NO synthase blockers, UK14304 elicited small contractions above 1 μM that were inhibited by 0.1 μM prazosin, but not influenced by 0.1 μM rauwolscine. At 3 μM or higher concentrations, phenylephrine caused only modest relaxation (up to 7.4 ± 2.3%) of segments constricted with prostaglandin F(2α) in the presence of prazosin, which was abolished with 0.1 μM BRL44408. Furthermore, BRL44408 did not increase contractions induced with 1 μM phenylephrine. These results confirm that α(1)- but not α(2)-adrenoceptors are expressed on aortic smooth muscle cells, whereas endothelial cells only express α(2)-adrenoceptors. Moreover, phenylephrine exerted a very modest relaxing effect through nonspecific stimulation of α(2)-adrenoceptors, but only at concentrations higher than 1 μM. It is concluded that the high basal output of NO in the isolated mouse aorta is not due to stimulation of α-adrenoceptors.
authors.affiliation: Division of Pharmacology, University of Antwerp, Antwerp, Belgium. Johanna.vanLangen@ua.ac.be
authors.forename: Johanna T H
authors.initials: JT
authors.lastname: van Langen
authors.forename: Cor E
authors.initials: CE
authors.lastname: Van Hove
authors.forename: Dorien M
authors.initials: DM
authors.lastname: Schrijvers
authors.forename: Wim
authors.initials: W
authors.lastname: Martinet
authors.forename: Guido R Y
authors.initials: GR
authors.lastname: De Meyer
authors.forename: Paul
authors.initials: P
authors.lastname: Fransen
authors.forename: Hidde
authors.initials: H
authors.lastname: Bult
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D000068438:Brimonidine Tartrate; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology; D054833:Isoindoles / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D010656:Phenylephrine / Q000008:administration & dosage / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D011810:Quinoxalines / Q000008:administration & dosage / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects* / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D007093:Imidazoles; D054833:Isoindoles; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D015016:Yohimbine; D009569:Nitric Oxide; D000068438:Brimonidine Tartrate; D019001:Nitric Oxide Synthase; D011224:Prazosin; C072125:BRL 44408