期刊
CARDIOVASCULAR RESEARCH
卷 99, 期 1, 页码 156-163出版社
OXFORD UNIV PRESS
DOI: 10.1093/cvr/cvt072
关键词
Adenosine; Microcirculation; Nitric oxide; Potassium channels; Vasodilation
资金
- National Institutes of Health [EY018420]
- Kruse Chair Endowment Fund
Adenosine is a potent vasodilator contributing to cerebral blood flow regulation during metabolic stress. However, the distribution of adenosine receptor subtypes and underlying signalling mechanisms for dilation of pial arterioles remain unclear. The present study aimed at addressing these issues. Isolated porcine pial arterioles were subjected to study of vasomotor function, localization of adenosine receptors, and production of nitric oxide (NO). Concentration-dependent vasodilation to adenosine was inhibited by A(2A) receptor antagonist ZM241385 but not by A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine. A(2A) receptors were detected in endothelium and smooth muscle of pial arterioles via immunohistochemistry. Adenosine significantly increased arteriolar production of NO, and the induced dilation was insensitive to K-ATP channel blocker glibenclamide but was attenuated by endothelial denudation, NO synthase inhibitor l-NAME, or guanylyl cyclase inhibitor ODQ in a similar manner. Both inward rectifier potassium (K-ir) channel inhibitor barium and cAMP signalling inhibitor Rp-8-Br-cAMPS attenuated adenosine-induced dilation. In the presence of l-NAME or the absence of endothelium, addition of Rp-8-Br-cAMPS but not barium further reduced adenosine-induced responses. Barium diminished endothelium-independent vasodilation to NO donor sodium nitroprusside. Comparable to the adenosine-induced response, vasodilation to A(2A) receptor agonist CGS21680 was attenuated by endothelial removal, ZM241385, l-NAME, barium, or Rp-8-Br-cAMPS, but not by glibenclamide. Adenosine evokes dilation of porcine pial arterioles via parallel activation of endothelial and smooth muscle A(2A) receptors. Stimulation of endothelial NO production activates smooth muscle guanylyl cyclase for vasodilation by opening K-ir channels. Adenosine also activates smooth muscle cAMP signalling leading to vasodilation.
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