A novel S-nitrosothiol (RIG200) causes prolonged relaxation in dorsal hand veins with damaged endothelium

N Sogo, I B Wilkinson, H MacCallum, S Q Khan, F E Strachan, D E Newby, I L Megson, D J Webb

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Reduced nitric oxide bioavailability caused by endothelial dysfunction or damage is a contributory factor in the initiation and progression of a number of cardiovascular diseases. Delivery of exogenous nitric oxide is an attractive therapeutic option, but current agents lack selectivity for areas of endothelial damage. We tested the hypothesis that a novel nitric oxide donor drug, N-(S-nitroso-N-acetylpenicillamine)-2-amino-2-deoxy-1,3,4,6-tetra-O-acet yl-P-glucopyranose [RIG200], which has selective effects in endothelium-denuded isolated arteries in vitro, would exert similar effects in dorsal hand veins with experimentally damaged endothelium in vivo.

METHODS: Venodilator responses to sodium nitroprusside and RIG200 were compared in two groups of healthy volunteers (age range, 18 to 63 years; n = 7 for each group) in norepinephrine 70% maximum effective concentration (EC70) preconstricted hand veins with use of the Aellig technique. In this doubleblind study, subjects were randomly assigned to receive either sodium nitroprusside or RIG200 (infusions of 0.06 and 6 nmol/min into the hand vein) before and 2 days after 15 minutes of local venous irription with distilled water. Endothelial function was assessed in all subjects on both visits with use of the endothelium-dependent vasodilator acetylcholine (1 nmol/min).

RESULTS: Irrigation of hand veins with distilled water abolished endothelium-dependent dilatation in response to acetylcholine in both study groups (n = 14) but did not affect the amplitude or duration of responses to the conventional nitric oxide donor sodium nitroprusside (P = .87; n = 7). However, responses to RIG200 were significantly prolonged during the washout phase (30 minutes) in veins after water irrigation (P = .02; n = 7).

CONCLUSION: These studies confirm that RIG200 has prolonged effects in veins with damaged endothelium, a characteristic that might be exploited therapeutically to target nitric oxide delivery to damaged blood vessels.

Original languageEnglish
Pages (from-to)75-81
Number of pages7
JournalClinical pharmacology and therapeutics
Volume68
Issue number1
DOIs
Publication statusPublished - 23 Jul 2000

Keywords

  • Acetylcholine
  • Adult
  • Area Under Curve
  • Double-Blind Method
  • Endothelium, Vascular
  • Humans
  • Infusions, Intravenous
  • Male
  • Mercaptoethanol
  • Middle Aged
  • Nitroprusside
  • Nitroso Compounds
  • Reference Values
  • S-Nitrosothiols
  • Therapeutic Irrigation
  • Time Factors
  • Vasodilation
  • Vasodilator Agents
  • Water

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