Journal
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Volume 301, Issue 4, Pages H1369-H1377Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00556.2011
Keywords
adenosine; astrocytes; neurovascular coupling; neurovascular unit; pial vessels
Funding
- American Heart Association [AHA-0635337N]
- National Heart, Lung, and Blood Institute [HL-088259]
- Juvenile Diabetes Research Foundation [JDRF-3-2008-462]
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Vetri F, Xu H, Mao L, Paisansathan C, Pelligrino DA. ATP hydrolysis pathways and their contributions to pial arteriolar dilation in rats. Am J Physiol Heart Circ Physiol 301: H1369-H1377, 2011. First published July 29, 2011; doi: 10.1152/ajpheart.00556.2011.-ATP is thought to be released to the extracellular compartment by neurons and astrocytes during neural activation. We examined whether ATP exerts its effect of promoting pial arteriolar dilation (PAD) directly or upon conversion (via ecto-nucleotidase action) to AMP and adenosine. Blockade of extracellular direct ATP to AMP conversion, with ARL-67156, significantly reduced sciatic nerve stimulation-evoked PADs by 68%. We then monitored PADs during suffusions of ATP, ADP, AMP, and adenosine in the presence and absence of the following: 1) the ecto-5'-nucleotidase inhibitor alpha,beta-methylene adenosine 5'-diphosphate (AOPCP), 2) the A(2) receptor blocker ZM 241385, 3) the ADP P2Y(1) receptor antagonist MRS 2179, and 4) ARL-67156. Vasodilations induced by 1 and 10 mu M, but not 100 mu M, ATP were markedly attenuated by ZM 241385, AOPCP, and ARL-67156. Substantial loss of reactivity to 100 mu M ATP required coapplications of ZM 241385 and MRS 2179. Dilations induced by ADP were blocked by MRS 2179 but were not affected by either ZM 241385 or AOPCP. AMP-elicited dilation was partially inhibited by AOPCP and completely abolished by ZM 241385. Collectively, these and previous results indicate that extracellular ATP-derived adenosine and AMP, via A(2) receptors, play key roles in neural activation-evoked PAD. However, at high extracellular ATP levels, some conversion to ADP may occur and contribute to PAD through P2Y(1) activation.
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