Rilmenidine-induced ocular hypotension: Role of imidazoline(1) and alpha(2) receptors

Purpose. To examine ocular actions by rilmenidine, an imidazoline(1) and alpha(2) adrenoceptor agonist. Methods. Intraocular pressure was measured in normal and sympathetically denervated rabbits by pneumatonometry. Electrically stimulated H-3-norepinephrine release from sympathetic nerves was determined in isolated, perfused rabbit iris-ciliary bodies. cAMP levels were evaluated in rabbit iris-ciliary bodies by radioimmunoassay. Ca2+ concentrations were measured in rabbit transformed nonpigmented ciliary epithelial cells by fluorescence ratio microscopy. Results. Topical, unilateral administration of rilmenidine produced hypotensive responses in normal rabbits which were antagonized by either bilaterally administered efaroxan, an imidazoline receptor antagonist or rauwolscine, an alpha(2) receptor antagonist. Sympathectomy also eliminated the ocular hypotensive response. Rilmenidine (0.001, 0.01, 0.1, 1 mu M) caused 5 +/- 1%, 18 +/- 5%, 35 +/- 10%, and 48 +/- 9% inhibition, respectively, of 3H-norepinephrine overflow whereas 10 mu M efaroxan or rauwolscine caused enhancement of norepinephrine release by 102 +/- 23% or 86 +/- 25%, respectively. Furthermore, pretreatment with efaroxan or rauwolscine partially antagonized the inhibition of norepinephrine release induced by rilmenidine. In other experiments, rilmenidine (1 mu M) inhibited isoproterenol-stimulated cAMP accumulation in rabbit iris-ciliary bodies by 43 +/- 9% which was antagonized by 10 mu M efaroxan or rauwolscine. Rilmenidine induced large increases in [Ca2+](i) in rabbit nonpigmented ciliary epithelial cells which were effectively antagonized by efaroxan or rauwolscine. Conclusions. These in vivo and in vitro data suggest that the ocular hypotensive activity induced by rilmenidine is due, in part, to suppression of sympathetic neuroeffector function in the rabbit ciliary body and that alpha(2) adrenergic receptors and/or imidazoline(1) receptors are involved.