title: The effect of purinergic signaling via the P2Y11receptor on vascular function in a rat model of acute inflammation.
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 P2Y11purinergic 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 P2Y11activator, NF546,decreased the LPS-induced aortic H2O2release and partially normalized the vasomotor function, namely reduced contractility and improved relaxation. The effect was abolished by co-treatment with the P2Y11inhibitor, NF340,and also after endothelium denudation. Importantly, NF546did not elicit an antioxidant effect by acting as a H2O2scavenger, suggesting that the beneficial outcome of this treatment on the vasculature is the consequence of P2Y11stimulation. In conclusion, purinergic P2Y11receptors 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.
authors.affiliation: Department of Functional Sciences - Pathophysiology, "Victor Babeş" University of Medicine and Pharmacy Timișoara, 2 Eftimie Murgu Sq., 300041, Timişoara, Romania.|Center for Translational Research and Systems Medicine, "Victor Babeş" University of Medicine and Pharmacy Timișoara, 2 Eftimie Murgu Sq., 300041, Timişoara, Romania.
authors.forename: Maria D
authors.initials: MD
authors.lastname: Dănilă
authors.affiliation: Department of Functional Sciences - Pathophysiology, "Victor Babeş" University of Medicine and Pharmacy Timișoara, 2 Eftimie Murgu Sq., 300041, Timişoara, Romania.
authors.forename: Andreea
authors.initials: A
authors.lastname: Privistirescu
authors.affiliation: Department of Functional Sciences - Pathophysiology, "Victor Babeş" University of Medicine and Pharmacy Timișoara, 2 Eftimie Murgu Sq., 300041, Timişoara, Romania.|Center for Translational Research and Systems Medicine, "Victor Babeş" University of Medicine and Pharmacy Timișoara, 2 Eftimie Murgu Sq., 300041, Timişoara, Romania.
authors.forename: Oana M
authors.initials: OM
authors.lastname: Duicu
authors.affiliation: Department of Functional Sciences - Pathophysiology, "Victor Babeş" University of Medicine and Pharmacy Timișoara, 2 Eftimie Murgu Sq., 300041, Timişoara, Romania.
authors.forename: Corina D
authors.initials: CD
authors.lastname: Rațiu
authors.affiliation: EA 4245 Cellules Dendritiques, Immunomodulation et Greffes, Université François-Rabelais de Tours, 37032, Tours, France.|Service de Cardiologie, Hôpital Trousseau, Centre Hospitalier Régional Universitaire de Tours, 37044, Tours, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Angoulvant
authors.affiliation: Department of Functional Sciences - Pathophysiology, "Victor Babeş" University of Medicine and Pharmacy Timișoara, 2 Eftimie Murgu Sq., 300041, Timişoara, Romania. daninamuntean@umft.ro.|Center for Translational Research and Systems Medicine, "Victor Babeş" University of Medicine and Pharmacy Timișoara, 2 Eftimie Murgu Sq., 300041, Timişoara, Romania. daninamuntean@umft.ro.
authors.forename: Danina M
authors.initials: DM
authors.lastname: Muntean
authors.affiliation: Department of Functional Sciences - Pathophysiology, "Victor Babeş" University of Medicine and Pharmacy Timișoara, 2 Eftimie Murgu Sq., 300041, Timişoara, Romania.|Center for Translational Research and Systems Medicine, "Victor Babeş" University of Medicine and Pharmacy Timișoara, 2 Eftimie Murgu Sq., 300041, Timişoara, Romania.
authors.forename: Adrian
authors.initials: A
authors.lastname: Sturza
mesh_terms: D000208:Acute Disease; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D004164:Diphosphonates / Q000494:pharmacology; D004195:Disease Models, Animal; D006861:Hydrogen Peroxide / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000633:toxicity*; D009282:Naphthalenesulfonates / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: C546599:4,4'-(carbonylbis(imino-3,1-phenylenecarbonylimino-3,1-(4-methylphenylene)carbonylimino))bis(1,3-xylene-alpha,alpha'-diphosphonic acid); D004164:Diphosphonates; D008070:Lipopolysaccharides; D009282:Naphthalenesulfonates; D018048:Receptors, Purinergic P2; D006861:Hydrogen Peroxide
keywords: Endothelial dysfunction; Inflammation; Purinergic P2Y11 receptors; Rat aorta; Reactive oxygen species