Functional and molecular evidence of adenosine A(2A) receptor in coronary arteriolar dilation to adenosine
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abstract
Adenosine is a potent vasodilator implicated in the regulation of coronary microvascular diameter during metabolic stress. However, the specific adenosine receptors and underlying mechanism responsible for the dilation of coronary microvessels to adenosine remains to be elucidated. Thus, pig subepicardial coronary arterioles (<100 m) were isolated, cannulated, and pressurized without flow for in vitro study. All vessels developed basal tone and dilated concentration-dependently to adenosine. Disruption of endothelium and inhibition of nitric oxide (NO) synthase by L-NAME produced identical attenuation of adenosine-induced dilation. KATP channel inhibitor glibenclamide further reduced the dilation of denuded vessels. cAMP antagonist Rp-8-Br-cAMP blocked vasodilation to forskolin, but failed to inhibit vasodilation to adenosine. Coronary dilation to adenosine was blocked by a selective adenosine A2A receptor antagonist ZM241385, but was not altered by an A1 receptor antagonist, DPCPX. Reverse transcription-polymerase chain reaction study revealed that A2A receptor mRNA was expressed in microvessels but not in cardiac myocytes; A1 receptor expression was observed only in cardiac myocytes. These results suggest that adenosine-induced dilation of coronary arterioles is mediated predominantly by A2A receptors. Activation of these receptors elicits vasodilation by endothelial release of NO and by smooth muscle opening of KATP channels in a cAMP-independent manner. 2001 Wiley-Liss, Inc.
