Endothelial dysfunction in aging animals: the role of poly(ADP-ribose) polymerase activation

Pacher, P., Mabley, Jon, Soriano, F.G., Liaudet, L., Komjati, K. and Szabo, C. (2002) Endothelial dysfunction in aging animals: the role of poly(ADP-ribose) polymerase activation British Journal of Pharmacology, 135 (6). pp. 1347-1350. ISSN 0007-1188

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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.

Item Type: Journal article
Uncontrolled Keywords: Aging; cardiac function; endothelial dysfunction; poly(ADP ribose) polymerase
Subjects: A000 Medicine > A300 Clinical Medicine
DOI (a stable link to the resource): 10.1038/sj.bjp.0704627
Faculties: Faculty of Science and Engineering > School of Pharmacy and Biomolecular Sciences
Depositing User: editor spbs
Date Deposited: 01 Dec 2006
Last Modified: 26 Mar 2015 12:14
URI: http://eprints.brighton.ac.uk/id/eprint/882

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