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The effect of purinergic signaling via the P2Y11 receptor on vascular function in a rat model of acute inflammation

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Abstract

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 P2Y11 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 (H2O2) was also recorded. The P2Y11 activator, NF546, decreased the LPS-induced aortic H2O2 release and partially normalized the vasomotor function, namely reduced contractility and improved relaxation. The effect was abolished by co-treatment with the P2Y11 inhibitor, NF340, and also after endothelium denudation. Importantly, NF546 did not elicit an antioxidant effect by acting as a H2O2 scavenger, suggesting that the beneficial outcome of this treatment on the vasculature is the consequence of P2Y11 stimulation. In conclusion, purinergic P2Y11 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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Acknowledgements

The study was Funded by the PII-C3-TC-2015-15132-06 university internal research Grant.

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Authors and Affiliations

  1. Department of Functional Sciences - Pathophysiology, “Victor Babeş” University of Medicine and Pharmacy Timișoara, 2 Eftimie Murgu Sq., 300041, Timişoara, Romania

    Maria D. Dănilă, Andreea Privistirescu, Oana M. Duicu, Corina D. Rațiu, Danina M. Muntean & Adrian Sturza

  2. Center for Translational Research and Systems Medicine, “Victor Babeş” University of Medicine and Pharmacy Timișoara, 2 Eftimie Murgu Sq., 300041, Timişoara, Romania

    Maria D. Dănilă, Oana M. Duicu, Danina M. Muntean & Adrian Sturza

  3. EA 4245 Cellules Dendritiques, Immunomodulation et Greffes, Université François-Rabelais de Tours, 37032, Tours, France

    Denis Angoulvant

  4. Service de Cardiologie, Hôpital Trousseau, Centre Hospitalier Régional Universitaire de Tours, 37044, Tours, France

    Denis Angoulvant

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  1. Maria D. Dănilă
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  2. Andreea Privistirescu
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  3. Oana M. Duicu
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Correspondence to Danina M. Muntean.

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Dănilă, M.D., Privistirescu, A., Duicu, O.M. et al. The effect of purinergic signaling via the P2Y11 receptor on vascular function in a rat model of acute inflammation. Mol Cell Biochem 431, 37–44 (2017). https://doi.org/10.1007/s11010-017-2973-5

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  • DOI: https://doi.org/10.1007/s11010-017-2973-5

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