Homocysteine induced impairment of nitric oxide-dependent vasorelaxation is reversible by the superoxide dismutase mimetic TEMPOL

Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
Davy HucksMagdi M Yaqoob

Abstract

Elevated plasma homocysteine concentrations in renal patients are associated with accelerated cardiovascular disease. The mechanism(s) by which homocysteine acts remains unclear however, evidence implicates a role involving endothelial dysfunction. Rat femoral arteries after acute or 4-h pre-incubation with racemic D,L-homocysteine (100 microM) were mounted on a myograph, pre-constricted with phenylephrine (10 microM) and responses to acetylcholine-dependent vasorelaxation examined. The incubations were repeated in the presence of indomethacin (10 microM), omega-nitro-L-arginine methyl ester (100 microM), L-arginine (100 microM), tetrahydrobiopterin (1 microM), catalase (1200 U/ml), ebselen, a peroxynitrite chelator (20 microM) and TEMPOL, a superoxide dismutase mimetic (1 mM). Results are shown as means+/-standard error, expressed as per cent relaxation to acetylcholine added (nmol/l). Increasing concentrations of homocysteine had no affect when added directly to basally relaxed or pre-constricted freshly isolated vessels. However, 4-h pre-incubation with or without homocysteine significantly shifted the acetylcholine EC(50) (EC(50) was defined as the concentration of acetylcholine that caused relaxation of the phenylephrine c...Continue Reading

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Citations

Mar 6, 2009·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Tamehachi NamikoshiNaoki Kashihara
Dec 30, 2008·Pharmacological Reviews·Christopher S Wilcox, Adam Pearlman
Jan 24, 2007·Physiological Reviews·Pál PacherLucas Liaudet
May 15, 2013·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Kamil KarolczakCezary Watala
Mar 3, 2009·Free Radical Biology & Medicine·Michele M CastroJose E Tanus-Santos
Nov 8, 2016·Microvascular Research·Serena MaterazziRiccardo Patacchini
Feb 29, 2008·Dalton Transactions : an International Journal of Inorganic Chemistry·Arvi Rauk
Apr 18, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Nithya NarayananSuresh C Tyagi
Jan 31, 2006·Free Radical Biology & Medicine·Helen R GriffithsHilary J Powers

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