Abstract:
:1. Pre-eclampsia is a serious pregnancy disorder associated with widespread activation of the maternal vascular endothelium. Recent evidence implicates a role for oxidative stress in the aetiology of this condition. 2. Reactive oxygen species, particularly superoxide anions, invokes endothelial cell activation through many pathways. 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). 3. We have studied whether the loss of endothelial function in pre-eclampsia is dependent on PARP activity. Endothelium-dependent responses of myometrial arteries were tested following exposure to either plasma from women with pre-eclampsia or normal pregnant women in the presence and absence of a novel potent inhibitor of PARP, PJ34. Additional effects of plasma and PJ34 inhibition were identified in microvascular endothelial cell cultures. 4. In myometrial arteries, PARP inhibition blocked the attenuation of endothelium-dependent responses following exposure to plasma from women with pre-eclampsia. In endothelial cell cultures, plasma from pre-eclamptics induced measurable oxidative stress and a concomitant increase in PARP activity and reduction in cellular ATP. Again, these biochemical changes were reversed by PJ34. 5. These results suggest that PARP activity plays a pathogenic role in the development of endothelial dysfunction in pre-eclampsia and promotes PARP inhibition as a potential therapy in this condition.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Crocker IP,Kenny LC,Thornton WA,Szabo C,Baker PNdoi
10.1038/sj.bjp.0706055subject
Has Abstractpub_date
2005-03-01 00:00:00pages
772-80issue
6eissn
0007-1188issn
1476-5381pii
0706055journal_volume
144pub_type
杂志文章abstract::1. The effect of several metabotropic ligands and di- or tripeptides were tested on the binding of [3H]-L(+)-2-amino-4-phosphonobutyric acid ([3H]-L-AP4) on rat mGlu4 receptor. For selected compounds, the functional activity was determined on this receptor using the guanosine-5'[gamma-35S]-thiotriphosphate [gamma-35S]...
journal_title:British journal of pharmacology
pub_type: 临床试验,杂志文章
doi:10.1038/sj.bjp.0702885
更新日期:1999-11-01 00:00:00
abstract::Cyclo-oxygenase (COX) inhibitors potentiate opioid inhibition of GABAergic synaptic transmission in rat periaqueductal grey (PAG) (Vaughan et al., 1997). In the present study, the relative contribution of cyclo-oxygenase-1 (COX-1) and COX-2 inhibition to this phenomenon was examined by use of whole-cell patch clamp re...
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pub_type: 杂志文章
doi:10.1038/sj.bjp.0701818
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journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1987.tb08961.x
更新日期:1987-02-01 00:00:00
abstract::1. The action of angiotensin on the circular and longitudinal muscle of the human colon has been studied in vitro. The ED50 value (g/ml) of circular muscle was 8.7 x 10(-8) and of longitudinal muscle 3.1 x 10(-8), while the corresponding figures for acetylcholine were 1.6 x 10(-6) and 1.1 x 10(-6), respectively. Angio...
journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1970.tb09553.x
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abstract::1. Vasorelaxant properties of three nitric oxide (NO) donor drugs (glyceryl trinitrate, sodium nitroprusside and spermine NONOate) in mouse aorta (phenylephrine pre-contracted) were compared with those of endothelium-derived NO (generated with acetylcholine), NO free radical (NO*; NO gas solution) and nitroxyl ion (NO...
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doi:10.1038/sj.bjp.0704269
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doi:10.1111/j.1476-5381.1995.tb16394.x
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pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb12668.x
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pub_type: 杂志文章,评审
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pub_type: 杂志文章
doi:10.1038/sj.bjp.0700857
更新日期:1997-01-01 00:00:00
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pub_type: 杂志文章
doi:10.1038/sj.bjp.0703104
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pub_type: 杂志文章
doi:10.1111/j.1476-5381.1986.tb11138.x
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1981.tb09153.x
更新日期:1981-04-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb06916.x
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pub_type: 杂志文章
doi:10.1038/sj.bjp.0701250
更新日期:1997-08-01 00:00:00
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pub_type: 杂志文章,评审
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pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13608.x
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journal_title:British journal of pharmacology
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journal_title:British journal of pharmacology
pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1038/sj.bjp.0705101
更新日期:2003-02-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15460.x
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pub_type: 杂志文章
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abstract::The modulation of the gamma-aminobutyric acidA (GABAA) receptor by alphaxalone has been investigated by use of voltage-clamp recordings from enzymatically isolated bovine chromaffin cells maintained in cell culture. Alphaxalone (greater than 30 nM) reversibly and dose-dependently potentiated the amplitude of membrane ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1987.tb11198.x
更新日期:1987-03-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1985.tb10563.x
更新日期:1985-07-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
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更新日期:2008-11-01 00:00:00