Prolonged effect of a novel S-nitrosated glyco-amino acid in endothelium-denuded rat femoral arteries: potential as a slow release nitric oxide donor drug

British Journal of Pharmacology
I L MegsonA R Butler

Abstract

1. The vasodilator properties of a novel S-nitrosated glyco-amino acid (RIG200) were investigated in isolated rat femoral arteries and compared with those of the parent S-nitrosothiol compound, S-nitroso-N-acetylpenicillamine (SNAP). 2. Spectrophotometric analysis revealed that 2.5 mM solutions of RIG200 decomposed more slowly (half-life (t1/2) = 216.2 +/- 26.7 min) than SNAP (t1/2 = 37.2 +/- 13.8 min) in Krebs buffer at 24 degrees C. Furthermore, the rate of decomposition of SNAP, but not of RIG200, was significantly reduced by the Cu(I) chelator, neocuproine. We concluded that the relative stability of RIG200 is due, at least in part, to its resistance to trace Cu(I)-catalyzed decomposition. Nitric oxide (NO) generation from SNAP and RIG200 was confirmed by use of an NO electrode. 3. Experiments to investigate the vasodilator effects of RIG200 were carried out on isolated femoral arteries taken from adult male Wistar rats (400-550 g). Lengths of artery (7-8 mm long) were cannulated, dissected free and perfused at constant flow rate (0.6 ml min-1) with Krebs buffer. Vessels were precontracted with phenylephrine (10.2 +/- 0.3 microM) and developed pressures of 91.8 +/- 4 mmHg, detected upstream by a differential pressure transd...Continue Reading

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Citations

Aug 4, 2005·Journal of the American Chemical Society·Yi-Lei ZhaoEric J Toone
Dec 19, 2000·Biochemical and Biophysical Research Communications·N SogoI L Megson
May 9, 2002·Expert Opinion on Investigational Drugs·Ian L Megson, David J Webb
Sep 17, 2004·Endothelium : Journal of Endothelial Cell Research·Márcia TerlukJamil Assreuy
Jul 5, 2005·Expert Opinion on Investigational Drugs·J C StocletA L Kleschyov
Apr 3, 2007·British Journal of Pharmacology·M R Miller, I L Megson
Feb 28, 2003·Expert Opinion on Investigational Drugs·M R Willmot, P M W Bath
Mar 29, 2000·Nitric Oxide : Biology and Chemistry·J HonoldM P Sherman
Sep 5, 2003·The Journal of Pharmacology and Experimental Therapeutics·Jacicarlos L AlencarBernard Muller
Apr 11, 2002·Chemical Reviews·Peng George WangAdam J Janczuk
May 4, 2021·Applied Microbiology and Biotechnology·Yu-Ming CaiLiang Yang

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