(Investigative Ophthalmology and Visual Science. 2005;46:2113-2119.)
© 2005 by The Association for Research in Vision and Ophthalmology, Inc.
DOI: 10.1167/iovs.04-1438
Requisite Roles of A2A Receptors, Nitric Oxide, and KATP Channels in Retinal Arteriolar Dilation in Response to Adenosine
Travis W. Hein,
Zhaoxu Yuan,
Robert H. Rosa, Jr, and
Lih Kuo
From the Department of Surgery, Division of Ophthalmology, Scott and White Eye Institute, Texas A&M University System Health Science Center, Temple, Texas.
PURPOSE. Adenosine is a potent vasodilator of retinal microvessels and is implicated to be a major regulator of retinal blood flow during metabolic stress. However, the receptor subtypes and the underlying signaling mechanism responsible for the dilation of retinal microvessels in response to adenosine remain unclear. In the present study, the roles of specific adenosine receptor subtypes, nitric oxide (NO), and adenosine triphosphate (ATP)–sensitive K+ (KATP) channels in adenosine-induced dilation of retinal arterioles in vitro were examined.
METHODS. Porcine second-order retinal arterioles (40–70 µm in internal diameter) were isolated, cannulated, and pressurized to 55 cmH2O luminal pressure without flow. Diameter changes in response to agonists were recorded by using videomicroscopic techniques.
RESULTS. All vessels exhibited basal tone and dilated dose dependently in reaction to adenosine, N6-cyclopentyladenosine (an adenosine A1 receptor agonist), and 2-[p-(2-carboxyethyl)]phenylethyl-amino-5'-N-ethylcarboxamidoadenosine(CGS21680 an adenosine A2A receptor agonist). These responses were not altered by the selective adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine, but were significantly attenuated by the selective adenosine A2A receptor antagonist 4-(2-{7-amino-2-(2-furyl)[1,2,4]-triazolo[2,3-a] [1,3,5]triazin-5-ylamino}ethyl)phenol. Blockade of NO synthase, but not of cyclooxygenase or cytochrome P-450 epoxygenase, significantly attenuated the vasodilations in response to adenosine and CGS21680 The residual vasodilative reactions to both agonists was nearly abolished by the KATP channel inhibitor glibenclamide.
CONCLUSIONS. These data suggest that adenosine evokes retinal arteriolar dilation via activation of A2A receptors and subsequent production of NO and opening of KATP channels. A better understanding of the fundamental signaling pathways responsible for adenosine-induced dilation of retinal arterioles may help shed light on the possible mechanisms contributing to impaired retinal blood flow regulation in patients after retinal ischemia.
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Copyright © 2005 by the Association for Research in Vision and Ophthalmology
