PD128,907 Induces Ocular Hypotension in Rabbits: Involvement of D 2 /D 3 Dopamine Receptors and Brain Natriuretic Peptide

Abstract

The purpose of this study was to determine the potential role of brain natriuretic peptide (BNP) in the PD128,907 (a dopamine D₂/D₃ receptor agonist)-induced ocular hypotension in rabbits. The effects of topical application of PD128,907 (75, 250, 750 μg) on intraocular pressure (IOP) were investigated. The lowest dose (75 μg) did not alter IOP; while the higher doses (250 and 750 μg) reduced IOP bilaterally. The PD128,907 (250 μg)-induced ocular hypotension, which lasted 3 hours, could be blocked by raclopride (1000 μg), a dopamine D₂/D₃ receptor antagonist, as well as by sympathetic denervation. Aqueous humor inflow was reduced by intravitreal injection of PD128,907 (10 μg) by 67% at 1 and 2 hours, which then returned to baseline at 3 hours. Furthermore, topical application of PD128,907 (250 μg) elevated aqueous BNP levels by 3-fold at 30 minutes, 6-fold at 1 hour and 5-fold at 2 hours, which could be blocked by pretreatment with raclopride (250 μg). Taken together, PD128,907-induced ocular hypotension by activation of dopamine D₂/D₃ receptors. This action was associated with reduced aqueous humor inflow and increased aqueous BNP levels.