Cerebral Vasodilator Property of Poly(ADP-Ribose) Polymerase Inhibitor (PJ34) in the Neonatal and Adult Mouse Is Mediated by the Nitric Oxide Pathway
The poly(ADP-ribose) polymerase (PARP) inhibitor PJ34 has been reported to improve endothelial dysfunction in the peripheral system. We addressed the role of PJ34 on the vascular tone and vasoreactivity during development in the mouse brain. Blood flows were measured in the basilar trunk using ultra...
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MDPI AG
2020-09-01
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| Series: | International Journal of Molecular Sciences |
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| author | Philippe Bonnin Christiane Charriaut-Marlangue Julien Pansiot Alexandre Boutigny Jean-Marie Launay Valérie C. Besson |
| author_facet | Philippe Bonnin Christiane Charriaut-Marlangue Julien Pansiot Alexandre Boutigny Jean-Marie Launay Valérie C. Besson |
| author_sort | Philippe Bonnin |
| collection | DOAJ |
| description | The poly(ADP-ribose) polymerase (PARP) inhibitor PJ34 has been reported to improve endothelial dysfunction in the peripheral system. We addressed the role of PJ34 on the vascular tone and vasoreactivity during development in the mouse brain. Blood flows were measured in the basilar trunk using ultrasonography. Cerebral vasoreactivity or vasodilation reserve was estimated as a percentage increase in mean blood flow velocities (mBFV) recorded under normoxia-hypercapnia in control and after PJ34 administration. Non-selective and selective eNOS and nNOS inhibitors were used to evaluate the role of NO-pathway into the hemodynamic effects of PJ34. PJ34 increased mBFVs from 15.8 ± 1.6 to 19.1 ± 1.9 cm/s (<i>p</i> = 0.0043) in neonatal, from 14.6 ± 1.4 to 16.1 ± 0.9 cm/s (<i>p</i> = 0.0049) in adult, and from 15.7 ± 1.7 to 17.5 ± 2.0 cm/s (<i>p</i> = 0.0024) in aged mice 48 h after administration. These PJ34 values were similar to those measured in age-matched control mice under normoxia-hypercapnia. This recruitment was mediated through the activation of constitutive NO synthases in both the neonatal (38.2 ± 6.7 nmol/min/mg protein) and adult (31.5 ± 4.4 nmol/min/mg protein) brain, as compared to age-matched control brain (6.9 ± 0.4 and 6.3 ± 0.7 nmol/min/mg protein), respectively. In addition, quite selective eNOS inhibitor was able to inhibit the recruitment. PJ34 by itself is able to increase cerebral blood flow through the NO-pathway activation at least over 48 h after a single administration. |
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| language | English |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3b916a7e71fc481b830d1e05096e0dbe2023-11-20T12:58:28ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-09-012118656910.3390/ijms21186569Cerebral Vasodilator Property of Poly(ADP-Ribose) Polymerase Inhibitor (PJ34) in the Neonatal and Adult Mouse Is Mediated by the Nitric Oxide PathwayPhilippe Bonnin0Christiane Charriaut-Marlangue1Julien Pansiot2Alexandre Boutigny3Jean-Marie Launay4Valérie C. Besson5U1275, INSERM, F-75010, Physiologie Clinique—Explorations Fonctionnelles, Hopital Lariboisiere, Université de Paris, 2, Rue Ambroise Pare, 75010 Paris, FranceU1141 NeuroDiderot, INSERM, Hôpital Robert Debré, Université de Paris, 48 Boulevard Sérurier, 75019 Paris, FranceU1141 NeuroDiderot, INSERM, Hôpital Robert Debré, Université de Paris, 48 Boulevard Sérurier, 75019 Paris, FranceU1275, INSERM, F-75010, Physiologie Clinique—Explorations Fonctionnelles, Hopital Lariboisiere, Université de Paris, 2, Rue Ambroise Pare, 75010 Paris, FranceUMR-S942—Biomarqueurs Cardiovasculaires, Hopital Lariboisiere, Université de Paris, 2, Rue Ambroise Pare, 75010 Paris, FranceUMR-S1144—Optimisation Thérapeutique en Neuropsychopharmacologie, Faculté de Pharmacie de Paris, Université de Paris, 4 Avenue de l’Observatoire, 75006 Paris, FranceThe poly(ADP-ribose) polymerase (PARP) inhibitor PJ34 has been reported to improve endothelial dysfunction in the peripheral system. We addressed the role of PJ34 on the vascular tone and vasoreactivity during development in the mouse brain. Blood flows were measured in the basilar trunk using ultrasonography. Cerebral vasoreactivity or vasodilation reserve was estimated as a percentage increase in mean blood flow velocities (mBFV) recorded under normoxia-hypercapnia in control and after PJ34 administration. Non-selective and selective eNOS and nNOS inhibitors were used to evaluate the role of NO-pathway into the hemodynamic effects of PJ34. PJ34 increased mBFVs from 15.8 ± 1.6 to 19.1 ± 1.9 cm/s (<i>p</i> = 0.0043) in neonatal, from 14.6 ± 1.4 to 16.1 ± 0.9 cm/s (<i>p</i> = 0.0049) in adult, and from 15.7 ± 1.7 to 17.5 ± 2.0 cm/s (<i>p</i> = 0.0024) in aged mice 48 h after administration. These PJ34 values were similar to those measured in age-matched control mice under normoxia-hypercapnia. This recruitment was mediated through the activation of constitutive NO synthases in both the neonatal (38.2 ± 6.7 nmol/min/mg protein) and adult (31.5 ± 4.4 nmol/min/mg protein) brain, as compared to age-matched control brain (6.9 ± 0.4 and 6.3 ± 0.7 nmol/min/mg protein), respectively. In addition, quite selective eNOS inhibitor was able to inhibit the recruitment. PJ34 by itself is able to increase cerebral blood flow through the NO-pathway activation at least over 48 h after a single administration.https://www.mdpi.com/1422-0067/21/18/6569cerebral blood flowcerebral vasoreactivityarterial dilationmousebrainno synthase |
| spellingShingle | Philippe Bonnin Christiane Charriaut-Marlangue Julien Pansiot Alexandre Boutigny Jean-Marie Launay Valérie C. Besson Cerebral Vasodilator Property of Poly(ADP-Ribose) Polymerase Inhibitor (PJ34) in the Neonatal and Adult Mouse Is Mediated by the Nitric Oxide Pathway International Journal of Molecular Sciences cerebral blood flow cerebral vasoreactivity arterial dilation mouse brain no synthase |
| title | Cerebral Vasodilator Property of Poly(ADP-Ribose) Polymerase Inhibitor (PJ34) in the Neonatal and Adult Mouse Is Mediated by the Nitric Oxide Pathway |
| title_full | Cerebral Vasodilator Property of Poly(ADP-Ribose) Polymerase Inhibitor (PJ34) in the Neonatal and Adult Mouse Is Mediated by the Nitric Oxide Pathway |
| title_fullStr | Cerebral Vasodilator Property of Poly(ADP-Ribose) Polymerase Inhibitor (PJ34) in the Neonatal and Adult Mouse Is Mediated by the Nitric Oxide Pathway |
| title_full_unstemmed | Cerebral Vasodilator Property of Poly(ADP-Ribose) Polymerase Inhibitor (PJ34) in the Neonatal and Adult Mouse Is Mediated by the Nitric Oxide Pathway |
| title_short | Cerebral Vasodilator Property of Poly(ADP-Ribose) Polymerase Inhibitor (PJ34) in the Neonatal and Adult Mouse Is Mediated by the Nitric Oxide Pathway |
| title_sort | cerebral vasodilator property of poly adp ribose polymerase inhibitor pj34 in the neonatal and adult mouse is mediated by the nitric oxide pathway |
| topic | cerebral blood flow cerebral vasoreactivity arterial dilation mouse brain no synthase |
| url | https://www.mdpi.com/1422-0067/21/18/6569 |
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