X-Message-Number: 24871
Date: Tue, 19 Oct 2004 20:27:48 -0700 (PDT)
From: Doug Skrecky <>
Subject: PARP and endothelial dysfunction

Br J Pharmacol. 2002 Mar;135(6):1347-50
Endothelial dysfunction in aging animals: the role of poly(ADP-ribose)
polymerase activation.
  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.

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