TY - JOUR
T1 - Endothelial dysfunction in aging animals
T2 - The role of poly(ADP-ribose) polymerase activation
AU - Pacher, Pál
AU - Mabley, Jon G.
AU - Soriano, Francisco G.
AU - Liaudet, Lucas
AU - Komjáti, Katalin
AU - Szabó, Csaba
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - Aging
KW - Cardiac function
KW - Endothelial dysfunction
KW - Poly(ADP ribose) polymerase
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U2 - 10.1038/sj.bjp.0704627
DO - 10.1038/sj.bjp.0704627
M3 - Article
C2 - 11906946
AN - SCOPUS:0036215470
SN - 0007-1188
VL - 135
SP - 1347
EP - 1350
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
IS - 6
ER -