Cerebral Vasodilator Property of Poly(ADP-Ribose) Polymerase Inhibitor (PJ34) in the Neonatal and Adult Mouse Is Mediated by the Nitric Oxide Pathway

U1275, INSERM, F-75010, Physiologie Clinique—Explorations Fonctionnelles, Hopital Lariboisiere, Université de Paris, 2, Rue Ambroise Pare, 75010 Paris, France

U1141 NeuroDiderot, INSERM, Hôpital Robert Debré, Université de Paris, 48 Boulevard Sérurier, 75019 Paris, France

UMR-S942—Biomarqueurs Cardiovasculaires, Hopital Lariboisiere, Université de Paris, 2, Rue Ambroise Pare, 75010 Paris, France

⁴

UMR-S1144—Optimisation Thérapeutique en Neuropsychopharmacologie, Faculté de Pharmacie de Paris, Université de Paris, 4 Avenue de l’Observatoire, 75006 Paris, France

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

^‡

P.B., C.C.-M. and V.C.B. share authorship.

Int. J. Mol. Sci. 2020, 21(18), 6569; https://doi.org/10.3390/ijms21186569

Received: 28 July 2020 / Revised: 28 August 2020 / Accepted: 4 September 2020 / Published: 8 September 2020

(This article belongs to the Section Molecular Pharmacology)

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Abstract

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 (p = 0.0043) in neonatal, from 14.6 ± 1.4 to 16.1 ± 0.9 cm/s (p = 0.0049) in adult, and from 15.7 ± 1.7 to 17.5 ± 2.0 cm/s (p = 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. View Full-Text

Keywords: cerebral blood flow; cerebral vasoreactivity; arterial dilation; mouse; brain; no synthase

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Bonnin, P.; Charriaut-Marlangue, C.; Pansiot, J.; Boutigny, A.; Launay, J.-M.; Besson, V.C. Cerebral Vasodilator Property of Poly(ADP-Ribose) Polymerase Inhibitor (PJ34) in the Neonatal and Adult Mouse Is Mediated by the Nitric Oxide Pathway. Int. J. Mol. Sci. 2020, 21, 6569. https://doi.org/10.3390/ijms21186569

AMA Style

Bonnin P, Charriaut-Marlangue C, Pansiot J, Boutigny A, Launay J-M, Besson VC. 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. 2020; 21(18):6569. https://doi.org/10.3390/ijms21186569

Chicago/Turabian Style

Bonnin, Philippe, Christiane Charriaut-Marlangue, Julien Pansiot, Alexandre Boutigny, Jean-Marie Launay, and Valérie C. Besson. 2020. "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 21, no. 18: 6569. https://doi.org/10.3390/ijms21186569

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Cerebral Vasodilator Property of Poly(ADP-Ribose) Polymerase Inhibitor (PJ34) in the Neonatal and Adult Mouse Is Mediated by the Nitric Oxide Pathway

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