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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*

Journal of Cardiovascular Pharmacology: April 2013 - Volume 61 - Issue 4 - p 318–323
doi: 10.1097/FJC.0b013e318281fa2d
Original Article

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.

*Divisions of Pharmacology

Physiopharmacology, University of Antwerp, Antwerp, Belgium.

Reprints: Johanna van Langen, Division of Pharmacology, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp-Wilrijk, Belgium (e-mail: Johanna.vanLangen@ua.ac.be).

Supported by the University of Antwerp (GOA-BOF 2407) and the Fund for Scientific Research (FWO) Flanders (grant G.0293.10N). J. van Langen is supported by a PhD scholarship from the FWO Flanders.

The authors report no conflicts of interest.

Received November 08, 2012

Accepted December 06, 2012

© 2013 Lippincott Williams & Wilkins, Inc.