Pharmacological characterization of beta-adrenoceptor subtype involvement in the ocular hypotensive response to...

The decrease in intraocular pressure elicited by isoproterenol in ocular normotensive animals is widely recognized. The participation of the beta-adrenoceptor subtypes in mediating this ocular hypotensive response has, however, remained unclear, because previous studies have been limited to monitoring the activity of single, supramaximal doses of relatively selective beta 2-adrenoceptor agonists. The studies herein report a relatively extensive pharmacological characterization of beta 1- and beta 2-adrenoceptor involvement in ocular hypotension associated with beta-adrenergic stimulation in the pigmented rabbit. A beta 2-adrenoceptor mechanism was indicated by the following evidence: isoproterenol and relatively selective beta 2-adrenoceptor agonists produced ocular hypotension over a similar dose range (0.001-0.1%; beta 1-adrenoceptor agonists, at doses likely to confer beta 1-adrenoceptor specificity, did not cause a similar decrease in intraocular pressure; the ocular hypotensive response to isoproterenol was abolished by topical timolol and pindolol and the relatively selective beta 2-adrenoceptor antagonist ICI 118551, whereas the relatively selective beta 1-adrenoceptor antagonists metoprolol and betaxolol were topically inactive; intravenous injection of beta 1-adrenoceptor-specific doses of metoprolol and betaxolol had little effect on isoproterenol-induced ocular hypotension, whereas the response was antagonized by a beta 2-adrenoceptor-specific i.v. dose of ICI 118551. These pharmacological results are consistent with radioligand binding and beta-adrenoceptor-linked adenylate cyclase studies which indicate a predominantly beta 2-adrenoceptor population associated with the ocular ciliary processes. None of the beta-blockers themselves altered normal intraocular pressure in the pigmented rabbit.