Submitted on December 6, 2005
Accepted on February 10, 2006
Brimonidine Evokes Heterogeneous Vasomotor Response of Retinal Arterioles: Diminished Nitric Oxide-mediated Vasodilation When Size Goes Small
Robert H Rosa, Jr.1*, Travis W Hein1, Zhaoxu Yuan1, Wenjuan Xu1, Melissa I Pechal1, Ryan L Geraets1, Joseph M Newman1, and Lih Kuo1
1 Division of Ophthalmology, Scott & White Eye Institute, Texas A&M University System Health Science Center, Temple, TX, USA
* To whom correspondence should be addressed. E-mail: rrosa{at}swmail.sw.org.
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 i.d.) dilated dose-dependently to brimonidine (0.1 nM to 10 µM) with 10% dilation at the highest concentration. Second-order arterioles (50±1 µm i.d.) responded heterogeneously with either dilation or constriction. The incident and magnitude of vasoconstriction were increased with increasing brimonidine concentration. Administration of NO synthase inhibitor L-NAME 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 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 upon the concentration and vessel size, may alter local retinal blood flow.
