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T.W. Hein, W. Wang, R.H. Rosa, L. Kuo; Requisite Roles of A2A Receptors and KATP Channels in Retinal Arteriolar Dilation to Adenosine . Invest. Ophthalmol. Vis. Sci. 2003;44(13):327.
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Purpose: Adenosine has been implicated to be a major vasodilator mediating autoregulatory adjustments in retinal blood flow. Although in-vivo studies indicate that activation of ATP-sensitive potassium (KATP) channels is involved in the retinal vasodilation to adenosine, the localization and contribution of specific adenosine receptor subtypes and KATP channel subunits to the dilation of retinal microvessels to adenosine remain elusive. Since hemodynamic changes are known to influence vascular function and to produce confounding effects on vasomotor responses to agonists, herein we examined the direct action of adenosine on retinal arterioles in vitro and determined the molecular contributions of adenosine receptor subtypes and KATP channel subunits to this vascular response. Methods: Pig retinal arterioles (50-80 µm in situ) were isolated, cannulated, and pressurized to 55 cmH2O lumenal pressure without flow for functional studies. Diameter changes were recorded using videomicroscopic techniques. RT/PCR studies were performed to detect mRNA expression in microvessels. Results: All vessels developed basal tone at 37°C and dilated concentration-dependently to adenosine (0.1 nM to 0.1 mM), endothelium-independent vasodilator sodium nitroprusside (0.1 nM to 0.1 mM), and KATP channel opener pinacidil (0.1 µM to 10 µM). A selective adenosine A2A receptor antagonist ZM241385, but not an adenosine A1 receptor antagonist CPX, blocked the adenosine-induced vasodilation. Similar to ZM241385, the KATP channel antagonist glibenclamide inhibited vasodilation to adenosine, as well as to pinacidil. The inhibitory effects of glibenclamide and ZM241385 appeared to be specific because they did not alter vasodilation to sodium nitroprusside. RT/PCR analysis revealed mRNA expression of adenosine A2A receptors and KATP channel subunit Kir6.1 but not of A1 receptors and Kir6.2 in retinal arterioles. Conclusions: These functional data suggest that adenosine evokes retinal arteriolar dilation via activation of A2A receptors and subsequent opening of KATP channels. This conclusion is corroborated by the molecular data showing that retinal arterioles express adenosine A2A receptors and Kir6.1 subunit of KATP channels. Since ocular diseases such as glaucoma and diabetic retinopathy may be associated with ischemia and impaired retinal blood flow regulation, the dysfunction of adenosine A2A receptors and/or KATP channels may contribute to the pathophysiology of these ocular diseases.
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