The effect of purinergic signaling via the P2Y11 receptor on vascular function in a rat model of acute inflammation
There is a growing body of evidence pointing to the role of purinergic signaling in the development and progression of various conditions that have inflammation as a common pathogenetic denominator. The aim of the present study was to assess the involvement of P 2 Y 11 purinergic receptors in the re...
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Published in | Molecular and cellular biochemistry Vol. 431; no. 1-2; pp. 37 - 44 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
New York
Springer US
01.07.2017
|
Subjects | |
Online Access | Get full text |
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Summary: | There is a growing body of evidence pointing to the role of purinergic signaling in the development and progression of various conditions that have inflammation as a common pathogenetic denominator. The aim of the present study was to assess the involvement of P
2
Y
11
purinergic receptors in the regulation of vascular function in aortic segments obtained using an experimental model of acute inflammation, the lipopolysaccharide (LPS, 8 mg/kg, i.p)-treated rats. Twelve hours after LPS administration, thoracic aortas were isolated and used for studies of vascular reactivity in the organ bath and for the measurement of reactive oxygen species (ROS) generation, respectively. LPS treatment significantly increased contractility to phenylephrine and attenuated the endothelium-dependent relaxation of the vascular segments in response to acetylcholine; an increased production of hydrogen peroxide (H
2
O
2
) was also recorded. The P
2
Y
11
activator, NF
546,
decreased the LPS-induced aortic H
2
O
2
release and partially normalized the vasomotor function, namely reduced contractility and improved relaxation. The effect was abolished by co-treatment with the P
2
Y
11
inhibitor, NF
340,
and also after endothelium denudation. Importantly, NF
546
did not elicit an antioxidant effect by acting as a H
2
O
2
scavenger, suggesting that the beneficial outcome of this treatment on the vasculature is the consequence of P
2
Y
11
stimulation. In conclusion, purinergic P
2
Y
11
receptors stimulation improves vascular function and mitigates oxidative stress in the setting of acute systemic inflammation, revealing salutary effects and therapeutic potential in pathologies associated with endothelial dysfunction. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0300-8177 1573-4919 |
DOI: | 10.1007/s11010-017-2973-5 |