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This Article Full Text Full Text (PDF) All Versions of this Article: 291/1/H231    most recent 01281.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Rosa, R. H. Articles by Kuo, L. Search for Related Content PubMed PubMed Citation Articles by Rosa, R. H., Jr. Articles by Kuo, L.

Brimonidine evokes heterogeneous vasomotor response of retinal arterioles: diminished nitric oxide-mediated vasodilation when size goes small

¹Departments of Ophthamology and Surgery, Scott and White Eye Institute; and ²Department of Systems Biology and Translational Medicine, Texas A&M University System Health Science Center, Temple, Texas

Submitted 6 December 2005 ; accepted in final form 10 February 2006

Brimonidine, an ₂-adrenergic receptor (AR) agonist, has been employed in the treatment of glaucoma due to its beneficial effects on intraocular pressure reduction and neuroprotection. In addition, some studies have implicated that brimonidine might influence ocular blood flow; however, its effect on the retinal microcirculation has not been documented. Herein, we examined the vasomotor action of brimonidine on different branching orders of retinal arterioles in vitro and determined the contribution of the ₂-AR subtype and the role of endothelium-derived nitric oxide (NO) in this vasomotor response. First- and second-order retinal arterioles of pigs were isolated, cannulated, and pressurized for functional studies. Videomicroscopic techniques were employed to record diameter changes in response to brimonidine. RT-PCR was performed for detection of -AR and endothelial NO synthase (eNOS) mRNA in retinal arterioles. All first-order arterioles (82 ± 2 µm ID) dilated dose dependently to brimonidine (0.1 nM to 10 µM) with 10% dilation at the highest concentration. Second-order arterioles (50 ± 1 µm ID) responded heterogeneously with either dilation or constriction. The incidence and magnitude of vasoconstriction were increased with increasing brimonidine concentration. Administration of the NO synthase inhibitor N^G-nitro-L-arginine methyl ester abolished the brimonidine-induced vasodilation in first- and second-order arterioles. Regardless of vessel size, vasomotor responses (i.e., vasodilation and vasoconstriction) of retinal arterioles were sensitive to the ₂-AR antagonist rauwolscine. Consistent with the functional data, _2A-AR and eNOS mRNAs were detected in retinal arterioles. Collectively, our data demonstrate that brimonidine at clinical doses evokes a consistent NO-dependent vasodilation in first-order retinal arterioles but a heterogeneous response in second-order arterioles. These vasomotor responses are mediated by the activation of ₂-AR. It appears that brimonidine, depending on the concentration and vessel size, may alter local retinal blood flow.

retinal blood flow; retinal microcirculation