Potent a2A-Adrenoceptor–Mediated Vasoconstriction by Brimonidine in Porcine Ciliary Arteries

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 a2-adrenoceptor agonists brimonidine, apraclonidine, and oxymetazoline. To determine which subtypes of the a2-adrenoceptor mediate this contraction, antagonists subselective for the different a2-adrenoceptors were added to the vessel bath before concentration–response curves for brimonidine were obtained. The following a2-adrenoceptor antagonists were applied: BRL44408 (a2A-selective), ARC239 (a2Band a2C-selective), and prazosin (a2Band a2C-selective). RESULTS. The a2-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 (pKB) for BRL44408 (7.8), ARC 239 (5.8) and for prazosin (6.0) suggesting the presence of functional a2A-adrenoceptors. Moreover, there was a good correlation of pKB with ligand-binding affinity (pKi) of the a2A-adrenoceptor in the porcine eye tissue. CONCLUSIONS. The a2-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 a2A-adrenoceptor subtype mediates this contraction. (Invest Ophthalmol Vis Sci. 2001;42: 2049–2055)