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

Content Provider	Semantic Scholar
Author	Rosa, Robert H. Hein, Travis W. Yuan, Zhaoxu Xu, Wenjuan Pechal, Melissa I. Geraets, Ryan L. Newman, Joseph M. Kuo, Lih
Copyright Year	2006
Abstract	Brimonidine, an alpha2-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 alpha2-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 alpha-AR and endothelial NO synthase (eNOS) mRNA in retinal arterioles. All first-order arterioles (82 +/- 2 microm ID) dilated dose dependently to brimonidine (0.1 nM to 10 microM) with 10% dilation at the highest concentration. Second-order arterioles (50 +/- 1 microm 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 NG-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 alpha2-AR antagonist rauwolscine. Consistent with the functional data, alpha2A-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 alpha2-AR. It appears that brimonidine, depending on the concentration and vessel size, may alter local retinal blood flow.
Starting Page	142
Ending Page	146
Page Count	5
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://ajpheart.physiology.org/content/ajpheart/291/1/H231.full.pdf
Alternate Webpage(s)	http://ajpheart.physiology.org/content/ajpheart/291/1/h231.full.pdf
PubMed reference number	16489103v1
Volume Number	291
Issue Number	1
Journal	American journal of physiology. Heart and circulatory physiology
Language	English
Access Restriction	Open
Subject Keyword	Adrenergic Receptor Adrenergic alpha-Agonists Arginine Blood Vessel Tissue Diameter (qualifier value) Document completion status - Documented Esters Genetic Heterogeneity Glaucoma Hematological Disease Mechlorethamine Microcirculation NG-Nitroarginine Methyl Ester NOS3 gene NOS3 protein, human Neuroprotection Nitric Oxide Synthase Pathological Dilatation Rauwolscine Retina Retinal Diseases Retinaldehyde Structure of arteriole Vascular constriction (function) Vasodilation disorder brimonidine
Content Type	Text
Resource Type	Article