title: Endothelial dysfunction in aging animals: the role of poly(ADP-ribose) polymerase activation.
abstract: Recent work has demonstrated the production of reactive oxygen and nitrogen species in the vasculature of aging animals. Oxidant induced cell injury triggers the activation of nuclear enzyme poly(ADP ribose) polymerase (PARP) leading to endothelial dysfunction in various pathophysiological conditions (reperfusion, shock, diabetes). Here we studied whether the loss of endothelial function in aging rats is dependent upon the PARP pathway within the vasculature. Young (3 months-old) and aging (22 months-old) Wistar rats were treated for 2 months with vehicle or the PARP inhibitor PJ34. In the vehicle-treated aging animals there was a significant loss of endothelial function, as measured by the relaxant responsiveness of vascular rings to acetylcholine. Treatment with PJ34, a potent PARP inhibitor, restored normal endothelial function. There was no impairment of the contractile function and endothelium-independent vasodilatation in aging rats. Furthermore, we found no deterioration in the myocardial contractile function in aging animals. Thus, intraendothelial PARP activation may contribute to endothelial dysfunction associated with aging.
authors.affiliation: Inotek Corporation, Suite 419E, 100 Cummings Center, Beverly, Massachusetts, MA 01915, USA.
authors.forename: Pál
authors.initials: P
authors.lastname: Pacher
authors.forename: Jon G
authors.initials: JG
authors.lastname: Mabley
authors.forename: Francisco G
authors.initials: FG
authors.lastname: Soriano
authors.forename: Lucas
authors.initials: L
authors.lastname: Liaudet
authors.forename: Katalin
authors.initials: K
authors.lastname: Komjáti
authors.forename: Csaba
authors.initials: C
authors.lastname: Szabó
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D010616:Phenanthrenes / Q000494:pharmacology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014652:Vascular Diseases / Q000201:enzymology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; C434926:N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride; D010616:Phenanthrenes; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases