PT  - JOURNAL ARTICLE
AU  - Hein, Travis W.
AU  - Belardinelli, Luiz
AU  - Kuo, Lih
TI  - Adenosine A<sub>2A</sub> Receptors Mediate Coronary Microvascular Dilation to Adenosine: Role of Nitric Oxide and ATP-Sensitive Potassium Channels
DP  - 1999 Nov 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 655--664
VI  - 291
IP  - 2
4099  - http://jpet.aspetjournals.org/content/291/2/655.short
4100  - http://jpet.aspetjournals.org/content/291/2/655.full
SO  - J Pharmacol Exp Ther1999 Nov 01; 291
AB  - Adenosine is a potent vasodilator that plays an important role in the regulation of coronary microvascular diameter. Although multiple adenosine receptor subtypes have been recently cloned, the specific adenosine receptor subtypes and the underlying mechanisms responsible for the vasodilation to adenosine in the coronary microcirculation remain unknown. Therefore, in the present study we determined the receptor subtypes for coronary arteriolar dilation to adenosine and investigated the role of nitric oxide (NO) and ATP-sensitive potassium (KATP) channels in this vasodilatory response. Pig coronary arterioles (50–100 μm in situ) were isolated, cannulated, and pressurized without flow for in vitro study. Arterioles developed basal tone and dilated in a concentration-dependent manner to adenosine and to adenosine receptor agonists (2S)-N6-[2-endo-norbornyl]adenosine (A1), 2-[p-(2-carboxyethyl)]phenylethyl-amino-5′-N-ethylcarboxamidoadenosine (CGS21680; A2A),N6-(3-iodobenzyl)adenosine-5′-N-methyluronamide (A3), and N-ethylcarboxamidoadenosine (nonselective adenosine receptor activation). The selective A2A receptor antagonist 4-(2-[7-amino-2-(2-furyl)[1,2,4]-triazolo[2,3-a][1,3,5]triazin-5-yl amino]ethyl)phenol attenuated vasodilation to adenosine and to all adenosine receptor agonists tested, suggesting that the vasodilatory responses were primarily mediated by A2A receptors. Adenosine- and CGS21680-induced dilations were attenuated in a similar manner by endothelial removal and by the NO synthase inhibitorNG-nitro-l-arginine methyl ester. In denuded vessels, both adenosine- and CGS21680-induced dilations were nearly abolished by the KATP channel inhibitor glibenclamide. The selective A2A agonist CGS21680 mechanistically mimics the vasodilation in response to adenosine. Collectively, our results suggest that the dilation of coronary arterioles to adenosine is mediated predominantly by A2Areceptors. Activation of this receptor subtype elicits vasodilation by endothelial release of NO and by the smooth muscle opening of KATP channels. The American Society for Pharmacology and Experimental Therapeutics