Selective suppression by bunazosin of alpha-adrenergic agonist evoked elevation of intraocular pressure in sympathectomized rabbit eyes

To determine whether there is alpha 1-adrenergic receptor heterogeneity associated with the regulation of intraocular pressure (IOP) and mydriasis in rabbits, the authors tested the hypothesis by characterizing the ability of the selective alpha 1-adrenergic antagonist, bunazosin, to block the ocular hypertensive and mydriatic responses to alpha 1-adrenoceptor stimulation by either norepinephrine (NE) or phenylephrine (PE). The effects of topical application of bunazosin on IOP and pupillary diameter were measured in unilateral superior cervical ganglionectomized (SCGX) rabbits after exposure to either NE or PE. Bunazosin (0.1%) alone only lowered the IOP in the normal eye and did not elicit a pupillary response on either side. NE (0.01-1.0%) by itself caused a concentration-dependent rise in IOP on both sides, but mydriasis did not occur on the normal side. In SCGX eyes, the sensitivity of the IOP response to NE increased tenfold over that measured on the normal side. Unlike on the normal side, concentration-dependent mydriatic responses occurred with 0.1 and 1% NE. After pretreatment with bunazosin (0.1%), neither NE (0.1%) nor PE (0.1%) evoked a rise in IOP. However, the mydriatic response to either one of these agonists in the SCGX eyes was less affected. By contrast, pretreatment with the alpha 2-adrenergic antagonist, 0.5% yohimbine, did not change the IOP increase elicited by 0.1% NE. These results suggest that the alpha 1-adrenergic receptors that regulate IOP and pupillary diameter are different from one another in the rabbit.