Skip Navigation LinksHome > April 2013 - Volume 61 - Issue 4 > Contribution of α-Adrenoceptor Stimulation by Phenylephrine...
Journal of Cardiovascular Pharmacology:
doi: 10.1097/FJC.0b013e318281fa2d
Original Article

Contribution of α-Adrenoceptor Stimulation by Phenylephrine to Basal Nitric Oxide Production in the Isolated Mouse Aorta

van Langen, Johanna T. H.*; Van Hove, Cor E.*; Schrijvers, Dorien M. PhD; Martinet, Wim PhD; De Meyer, Guido R. Y. PhD; Fransen, Paul PhD; Bult, Hidde PhD*

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Abstract

Abstract: In the mouse aorta, contractions evoked by the α1-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 α2-adrenoceptors. On a prostaglandin F contraction, the α2-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 α2-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 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 α1- but not α2-adrenoceptors are expressed on aortic smooth muscle cells, whereas endothelial cells only express α2-adrenoceptors. Moreover, phenylephrine exerted a very modest relaxing effect through nonspecific stimulation of α2-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.

© 2013 Lippincott Williams & Wilkins, Inc.

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