A new, potent poly(ADP-ribose) polymerase inhibitor improves cardiac and vascular dysfunction associated with advanced aging

Détails

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Etat: Public
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ID Serval
serval:BIB_EDCEF6840427
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
A new, potent poly(ADP-ribose) polymerase inhibitor improves cardiac and vascular dysfunction associated with advanced aging
Périodique
Journal of Pharmacology and Experimental Therapeutics
Auteur(s)
Pacher P., Vaslin A., Benko R., Mabley J. G., Liaudet L., Hasko G., Marton A., Batkai S., Kollai M., Szabo C.
ISSN
0022-3565 (Print)
Statut éditorial
Publié
Date de publication
11/2004
Volume
311
Numéro
2
Pages
485-91
Langue
anglais
Notes
Journal Article
Research Support, U.S. Gov't, P.H.S. --- Old month value: Nov
Résumé
Increased production of reactive oxygen and nitrogen species has recently been implicated in the pathogenesis of cardiac and endothelial dysfunction associated with atherosclerosis, hypertension, and aging. Oxidant-induced cell injury triggers the activation of nuclear enzyme poly(ADP-ribose) polymerase (PARP), which in turn contributes to cardiac and vascular dysfunction in various pathophysiological conditions including diabetes, reperfusion injury, circulatory shock, and aging. Here, we investigated the effect of a new PARP inhibitor, INO-1001, on cardiac and endothelial dysfunction associated with advanced aging using Millar's new Aria pressure-volume conductance system and isolated aortic rings. Young adult (3 months old) and aging (24 months old) Fischer rats were treated for 2 months with vehicle, or the potent PARP inhibitor INO-1001. In the vehicle-treated aging animals, there was a marked reduction of both systolic and diastolic cardiac function and loss of endothelial relaxant responsiveness of aortic rings to acetylcholine. Treatment with INO-1001 improved cardiac performance in aging animals and also acetylcholine-induced, nitric oxide-mediated vascular relaxation. Thus, pharmacological inhibition of PARP may represent a novel approach to improve cardiac and vascular dysfunction associated with aging.
Mots-clé
Aging/*physiology Animals Disease Models, Animal Enzyme Inhibitors/*pharmacology/therapeutic use Heart Diseases/prevention & control Heart Function Tests/*drug effects Indoles/*pharmacology/therapeutic use Male Poly(ADP-ribose) Polymerases/*antagonists & inhibitors Rats Rats, Inbred F344 Vascular Diseases/prevention & control Ventricular Remodeling/*drug effects
Pubmed
Web of science
Création de la notice
24/01/2008 18:01
Dernière modification de la notice
20/08/2019 17:15
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