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Abstract #6471 Published in IGR 3-2
Potent α2A-adrenoceptor-mediated vasoconstriction by brimonidine in porcine ciliary arteries
Wikberg-Matsson A; Simonsen UInvestigative Ophthalmology and Visual Science 2001; 42: 2049-2055
PURPOSE: An investigation into whether α2-adrenoceptor agonists induce contractions in the porcine ciliary artery 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 α2-adrenoceptor agonists brimonidine, apraclonidine, and oxymetazoline. To determine which subtypes of the α2-adrenoceptor mediate this contraction, antagonists subselective for the different α2-adrenoceptors were added to the vessel bath before concentration-response curves for brimonidine were obtained. The following α2-adrenoceptor antagonists were applied: BRL44408 (α2A-selective), ARC239 (α2B- and α2C-selective), and prazosin (α2B- and α2C-selective). RESULTS: The α2-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 artery, 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 (pKB) for BRL44408 (7.8), ARC239 (5.8), and for prazosin (6.0), suggesting the presence of functional α2a-adrenoceptors. Moreover, there was good correlation of pKB with ligand-binding affinity (pKi) of the α2A-adrenoceptor in the porcine eye tissue. CONCLUSIONS: The α2-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 α2A-adrenoceptor subtype mediates this contraction.
Dr A. Wikberg-Matsson, Department of Neuroscience, Ophthalmology, University Hospital, Uppsala, Sweden
Classification:
11.3.3 Apraclonidine, brimonidine (Part of: 11 Medical treatment > 11.3 Adrenergic drugs)
