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Potent _2A-Adrenoceptor–Mediated Vasoconstriction by Brimonidine in Porcine Ciliary Arteries

¹ From the Department of Neuroscience, Ophthalmology, University Hospital, Uppsala, Sweden; the ² Department of Neuroscience, Unit of Pharmacology, Uppsala University, Sweden; and the ³ Department of Pharmacology, University of Aarhus, Denmark.

PURPOSE. An investigation into whether ₂-adrenoceptor agonists induce contractions in the porcine ciliary arteries and to characterize the functional receptor subtype mediating these responses.

METHODS. Isolated arteries from the intraocular part of the porcine ciliary artery were suspended in microvascular myographs for isometric tension recording. The segments were contracted with the ₂-adrenoceptor agonists brimonidine, apraclonidine, and oxymetazoline. To determine which subtypes of the ₂-adrenoceptor mediate this contraction, antagonists subselective for the different ₂-adrenoceptors were added to the vessel bath before concentration–response curves for brimonidine were obtained. The following ₂-adrenoceptor antagonists were applied: BRL44408 (_2A-selective), ARC239 (_2B- and _2C-selective), and prazosin (_2B- and _2C-selective).

RESULTS. The ₂-adrenoceptor agonists induced vasoconstriction in the porcine ciliary artery with the following potency order (EC₅₀) expressed in nanomolar: brimonidine 2.11, oxymetazoline 5.26, and apraclonidine 13.0. As a reference, noradrenaline was tested, and its EC₅₀ was determined to be 247 nM in the ciliary artery. In the porcine ciliary arteries BRL44408, ARC239, and prazosin caused concentration-dependent and parallel rightward shifts of the concentration–response curves for brimonidine. Schild analyses for the antagonists against brimonidine yielded regression lines with slopes of unity and functional antagonist potencies (pK_B) for BRL44408 (7.8), ARC 239 (5.8) and for prazosin (6.0) suggesting the presence of functional _2A-adrenoceptors. Moreover, there was a good correlation of pK_B with ligand-binding affinity (pK_i) of the _2A-adrenoceptor in the porcine eye tissue.

CONCLUSIONS. The ₂-adrenoceptor agonists brimonidine, apraclonidine, and oxymetazoline are potent vasoconstrictors in the porcine ciliary artery. In the present work, it was shown for the first time that the _2A-adrenoceptor subtype mediates this contraction.

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