Centrally mediated ocular hypotension: potential role of imidazoline receptors.
These experiments sought to: (1) determine if alpha 2/I1 agonists that are topically active on the eye have similar effects on intraocular pressure when applied to the CNS and (2) ascertain whether these agents lower IOP, in part, via central alpha 2 receptors and/or imidazoline (I1) receptors. New Zealand White rabbits were fitted with chronic indwelling stainless-steel guide cannulas in several brain regions including the lateral ventricle, third ventricle (3V), or medullary intermediate reticular zone. Animals were allowed 5 days' recovery time prior to experiments measuring the effects of drugs on IOP via applanation pneumatonometry. Some animals were also pretreated with 400 micrograms of 6-hydroxydopamine injected into the lateral ventricle to determine the site of action of these alpha 2/I1 agonists. In initial experiments involving microinjection into the lateral ventricle, UK-14,304-18 evoked ocular hypotension that was inhibited by the alpha 2-antagonist rauwolscine but not by the I1-receptor antagonist efaroxan. Conversely, moxonidine and oxymetazoline were preferentially inhibited by efaroxan rather than by rauwolscine. Subsequently, experiments have shown that moxonidine and oxymetazoline, but not UK-14,304-18 will lower intraocular pressure when microinjected into the medullary intermediate reticular zone region and that efaroxan, but not rauwolscine, will inhibit ocular hypotension induced by moxonidine and oxymetazoline. Pretreatment with 6-hydroxydopamine (48 hours) completely eliminated the ocular hypotension induced by moxonidine. These preliminary data demonstrate that alpha 2- and I1-receptors in the brain mediate ocular hypotension induced by UK-14,304-18 and moxonidine/oxymetazoline, respectively. Moreover, the medullary intermediate reticular zone area of the brain stem is the probable presynaptic site mediating ocular hypotension induced by moxonidine and oxymetazoline.
Campbell
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Department of Biology, Morris Brown College, Atlanta, Georgia 30314-4140, USA.
Potter
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D000287:Administration, Topical; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D003315:Cornea / Q000378:metabolism; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D054755:Imidazoline Receptors; D007276:Injections, Intraventricular; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism; D009798:Ocular Hypertension / Q000503:physiopathology*; D011817:Rabbits; D011955:Receptors, Drug / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013563:Sympathectomy, Chemical; D015016:Yohimbine / Q000494:pharmacology
D001572:Benzofurans; D007093:Imidazoles; D054755:Imidazoline Receptors; D011955:Receptors, Drug; D015016:Yohimbine; C062597:efaroxan