Poly(ADP-ribose) polymerase inhibition prevents homocysteine-induced endothelial dysfunction in the isolated rat aorta

Pharmacology
Arda TasatargilGulay Sadan

Abstract

Recent studies have clearly shown that there is a relationship between hyperhomocysteinemia and endothelial dysfunction. However, the effect of poly(ADP-ribose) polymerase (PARP) inhibition on homocysteine (Hcy)-induced endothelial damage has not been investigated. In this study, we investigated whether the loss of endothelial function in rat aortic rings preincubated with Hcy is dependent upon the PARP pathway within the vasculature. Preincubation of rat aortic rings with Hcy (1 mmol/l; 180 min) significantly inhibited endothelium-dependent relaxation in this tissue. This inhibitory effect was significantly reduced in the presence of both superoxide dismutase (100 U ml(-1)) and catalase (100 U ml(-1)) together with Hcy. Similarly, preincubation for 180 min with either N-(6-oxo-5,6-dihydro-phenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride (PJ34; 3 micromol/l) or 3-aminobenzamide (3 mmol/l), structurally different PARP inhibitors, also significantly prevented the development of endothelial dysfunction induced by Hcy. Further incubation of aortic rings with these PARP inhibitors for 60 min after exposure to Hcy for 180 min, at least in part, improved the endothelium-dependent relaxation responses. Thus, our results suggest ...Continue Reading

Citations

Jul 13, 2013·Cardiovascular Drugs and Therapy·Qin YangCheuk-Man Yu
Sep 8, 2007·Antioxidants & Redox Signaling·Sanjana Dayal, Steven R Lentz
Apr 27, 2010·Biochemical Pharmacology·Vincenzo GiansantiA Ivana Scovassi
May 25, 2005·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Csaba Szabó
Apr 15, 2005·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Arda TasatargilGulay Sadan
Jun 17, 2014·Upsala Journal of Medical Sciences·Bedriniam YilmazArda Tasatargil
Aug 24, 2012·International Journal of Toxicology·Selvinaz DalakliogluArda Tasatargil
Aug 29, 2009·Journal of the Renin-angiotensin-aldosterone System : JRAAS·Arda TasatargilBedriniam Dalkiran
Dec 10, 2016·Frontiers in Neuroscience·Ján LehotskýPeter Kaplán
Jun 8, 2019·Pharmacological Reports : PR·Nazli Ece Gungor-OrdueriCiler Celik-Ozenci

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