PT - JOURNAL ARTICLE AU - Pál Pacher AU - Anne Vaslin AU - Rita Benkő AU - Jon G. Mabley AU - Lucas Liaudet AU - György Haskó AU - Anita Marton AU - Sándor Bátkai AU - Márk Kollai AU - Csaba Szabó TI - A New, Potent Poly(ADP-ribose) Polymerase Inhibitor Improves Cardiac and Vascular Dysfunction Associated with Advanced Aging AID - 10.1124/jpet.104.069658 DP - 2004 Nov 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 485--491 VI - 311 IP - 2 4099 - http://jpet.aspetjournals.org/content/311/2/485.short 4100 - http://jpet.aspetjournals.org/content/311/2/485.full SO - J Pharmacol Exp Ther2004 Nov 01; 311 AB - 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. The American Society for Pharmacology and Experimental Therapeutics