Requisite roles of A2A receptors, nitric oxide, and KATP channels in retinal arteriolar dilation in response to adenosine. Academic Article uri icon

abstract

  • 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(+) (K(ATP)) channels in adenosine-induced dilation of retinal arterioles in vitro were examined. METHODS: Porcine second-order retinal arterioles (40-70 mum in internal diameter) were isolated, cannulated, and pressurized to 55 cmH(2)O 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, N(6)-cyclopentyladenosine (an adenosine A(1) receptor agonist), and 2-[p-(2-carboxyethyl)]phenylethyl-amino-5'-N-ethylcarboxamidoadenosine(CGS21680; an adenosine A(2A) receptor agonist). These responses were not altered by the selective adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine, but were significantly attenuated by the selective adenosine A(2A) 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 K(ATP) channel inhibitor glibenclamide. CONCLUSIONS: These data suggest that adenosine evokes retinal arteriolar dilation via activation of A(2A) receptors and subsequent production of NO and opening of K(ATP) 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.

published proceedings

  • Invest Ophthalmol Vis Sci

author list (cited authors)

  • Hein, T. W., Yuan, Z., Rosa, R. H., & Kuo, L.

citation count

  • 66

complete list of authors

  • Hein, Travis W||Yuan, Zhaoxu||Rosa, Robert H||Kuo, Lih

publication date

  • June 2005