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Title
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Contribution of -adrenoceptor stimulation by phenylephrine to basal nitric oxide production in the isolated mouse aorta
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Author
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Abstract
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| In the mouse aorta, contractions evoked by the [alpha]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 [alpha]2-adrenoceptors. On a prostaglandin F2[alpha] contraction, the [alpha]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 [micro]M 2-[(4,5-Dihydro-1H-imidazol-2-yl)methyl]-2,3-dihydro-1-methyl-1H-isoindole (BRL44408) with a pKB' corresponding to [alpha]2-antagonism. In the presence of NO synthase blockers, UK14304 elicited small contractions above 1 [micro]M which were inhibited by 0.1 [micro]M prazosin, but not influenced by 0.1 [micro]M rauwolscine. At 3 [micro]M or higher concentrations, phenylephrine caused only modest relaxation (up to 7.4+/-2.3%) of segments constricted with prostaglandin F2[alpha] in the presence of prazosin, which was abolished with 0.1 [micro]M BRL44408. Furthermore, BRL44408 did not increase contractions induced with 1 [micro]M phenylephrine. These results confirm that [alpha]1- but not [alpha]2-adrenoceptors are expressed on aortic smooth muscle cells, while endothelial cells only express [alpha]2-adrenoceptors. Moreover, phenylephrine exerted a very modest relaxing effect through non-specific stimulation of [alpha]2-adrenoceptors, but only at concentrations higher than 1 [micro]M. It is concluded that the high basal output of NO in the isolated mouse aorta is not due to stimulation of [alpha]-adrenoceptors. |
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Language
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English
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Source (journal)
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Journal of cardiovascular pharmacology. - New York
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Publication
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New York
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2013
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ISSN
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0160-2446
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DOI
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10.1097/FJC.0B013E318281FA2D
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Volume/pages
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61
:4
(2013)
, p. 318-323
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ISI
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000317480300008
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Full text (Publisher's DOI)
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