May 2003
Volume 44, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2003
Activation of 2-Adrenergic Receptors by Bromonidine Evokes Nitric Oxide-Mediated Dilation of Retinal Microvessels
Author Affiliations & Notes
  • R.H. Rosa
    Department of Ophthalmology, Scott & White Clinic, Temple, TX, United States
  • T.W. Hein
    Department of Medical Physiology, Texas A&M University System Health Science Center, College Station, TX, United States
  • L. Kuo
    Department of Medical Physiology, Texas A&M University System Health Science Center, College Station, TX, United States
  • Footnotes
    Commercial Relationships  R.H. Rosa, None; T.W. Hein, None; L. Kuo, None.
  • Footnotes
    Support  Scott & White Research Foundation, NIH Grants NHLBI HL-55524, HL-48179, K02HL03693
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 958. doi:
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      R.H. Rosa, T.W. Hein, L. Kuo; Activation of 2-Adrenergic Receptors by Bromonidine Evokes Nitric Oxide-Mediated Dilation of Retinal Microvessels . Invest. Ophthalmol. Vis. Sci. 2003;44(13):958.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: The selective α2-adrenergic receptor (AR) agonist brimonidine tartrate has been employed in the treatment of glaucoma and is currently under investigation for ischemic optic neuropathy. The beneficial effects of brimonidine include a reduction in intraocular pressure and neuroprotection. However, the underlying mechanisms remain obscure. Some studies indicate an improvement in retinal blood flow. Herein, we examined the direct vasomotor action of brimonidine on retinal arterioles in vitro and determined the contribution of specific α-AR subtypes and the endothelium-derived vasodilator nitric oxide (NO) in this vasomotor reaction. Methods: Porcine retinal arterioles (40-80 µm in diameter in situ) were isolated for functional and molecular analysis. For functional studies, retinal arterioles were cannulated with micropipettes and pressurized to 55 cm H2O without flow. RT/PCR analysis was performed for detection of α1- and α2-adrenergic receptor mRNA in retinal arterioles. Results: All vessels developed basal tone at 37°C and dilated concentration-dependently to brimonidine (0.1 nM to 7 µM) and to endothelium-independent vasodilator sodium nitroprusside (0.1 nM to 0.1 mM). Changes in vessel diameter stabilized within 5 minutes after administration of each concentration of brimonidine. The highest concentration of brimonidine (7 µM) produced 29±7% of maximal dilation. An α2-AR antagonist rauwolscine, but not an α1-AR antagonist prazosin, abolished the brimonidine-induced vasodilation. Similar to rauwolscine, the NO synthase inhibitor L-NAME completely blocked the vasodilatory response. The inhibitory effects of rauwolscine and L-NAME appeared to be specific because they did not alter vasodilation to sodium nitroprusside. Consistent with the functional data, the α2-AR but not α1-AR mRNA was detected in retinal arterioles. Conclusions: The data suggest that brimonidine at clinical doses can evoke a modest vasodilatory response in retinal arterioles via activation of endothelial α2-AR and subsequent production of NO by endothelial cells. This apparent vasodilatory response may contribute to the neuroprotective effect of brimonidine.

Keywords: drug toxicity/drug effects • neuroprotection • nitric oxide 
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