| Contribution of PARP to endothelial dysfunction and hypertension in a rat model of pre-eclampsia. | |
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MedLine Citation:
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PMID: 22339234 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND AND PURPOSE: Under conditions of increased oxidative stress, such as pre-eclampsia and diabetes, overstimulation of PARP leads to endothelial dysfunction. Inhibition of PARP has been demonstrated to reverse the vascular dysfunction associated with diabetes in vivo. The present study was carried out to investigate the role of PARP in mediating the endothelial dysfunction associated with pre-eclampsia. EXPERIMENTAL APPROACH: Uteroplacental perfusion was surgically reduced in pregnant rats to produce the reduced uterine perfusion pressure (RUPP) rat model of pre-eclampsia and the PARP inhibitor, PJ34, was administered either before or after surgery. Mean arterial BP and vascular function were measured in normal pregnant (NP) and both control and PJ34-treated RUPP rats. Mesenteric vessels from NP rats were incubated with either 3% RUPP or NP plasma alone or in combination with PJ34. Finally, immunohistochemical staining was carried out to measure nitrotyrosine (byproduct of peroxynitrite) immunoreactivity. KEY RESULTS: RUPP rats were characterized by hypertension, fetal growth restriction and endothelial dysfunction when compared with NP rats. PJ34 administered in vivo before, but not after, surgery prevented the development of both endothelial dysfunction and hypertension. RUPP plasma-induced impaired vasorelaxation was prevented following co-incubation with PJ34 in vitro. Furthermore, the protective effect of PARP inhibition in vivo was accompanied by a reduction in nitrotyrosine immunoreactivity. CONCLUSIONS AND IMPLICATIONS: PJ34 prevented the development of both endothelial dysfunction and hypertension and reduced vascular nitrotyrosine immunoreactivity, thus suggesting a role for oxidative-nitrosative stress/PARP activation in the aberration in both vascular and haemodynamic function in this rat model of pre-eclampsia. |
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Authors:
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S K Walsh; F A English; I P Crocker; E J Johns; L C Kenny |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: British journal of pharmacology Volume: 166 ISSN: 1476-5381 ISO Abbreviation: Br. J. Pharmacol. Publication Date: 2012 Aug |
Date Detail:
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Created Date: 2012-07-10 Completed Date: 2012-11-29 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 7502536 Medline TA: Br J Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 2109-16 Citation Subset: IM |
Copyright Information:
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© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society. |
Affiliation:
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Anu Research Centre, Department of Obstetrics & Gynaecology, University College Cork, Cork University Maternity Hospital, Cork, Ireland. s.walsh@rgu.ac.uk |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Disease Models, Animal Endothelium, Vascular / drug effects, physiopathology* Enzyme Inhibitors / pharmacology, therapeutic use Female Hypertension / drug therapy, physiopathology* Mesenteric Arteries / drug effects, physiopathology Phenanthrenes / pharmacology, therapeutic use Poly(ADP-ribose) Polymerases / antagonists & inhibitors, physiology* Pre-Eclampsia / drug therapy, physiopathology* Pregnancy Rats Rats, Sprague-Dawley |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride; 0/Phenanthrenes; EC 2.4.2.30/Adprt protein, rat; EC 2.4.2.30/Poly(ADP-ribose) Polymerases |
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