A novel S-nitrosothiol (RIG200) causes prolonged relaxation in dorsal hand veins with damaged endothelium
- PMID: 10945318
- DOI: 10.1067/mcp.2000.107049
A novel S-nitrosothiol (RIG200) causes prolonged relaxation in dorsal hand veins with damaged endothelium
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.
Similar articles
-
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.Br J Pharmacol. 1997 Dec;122(8):1617-24. doi: 10.1038/sj.bjp.0701557. Br J Pharmacol. 1997. PMID: 9422806 Free PMC article.
-
S-nitrosothiols cause prolonged, nitric oxide-mediated relaxation in human saphenous vein and internal mammary artery: therapeutic potential in bypass surgery.Br J Pharmacol. 2000 Nov;131(6):1236-44. doi: 10.1038/sj.bjp.0703700. Br J Pharmacol. 2000. PMID: 11082133 Free PMC article.
-
Local venous response to N-desethylamiodarone in humans.Clin Pharmacol Ther. 2000 Jan;67(1):22-31. doi: 10.1067/mcp.2000.103822. Clin Pharmacol Ther. 2000. PMID: 10668850
-
S-Nitrosothiols: a class of nitric oxide-donor drugs.Clin Sci (Lond). 2000 May;98(5):507-20. Clin Sci (Lond). 2000. PMID: 10781381 Review.
-
Homocysteine, EDRF, and endothelial function.J Nutr. 1996 Apr;126(4 Suppl):1290S-4S. doi: 10.1093/jn/126.suppl_4.1290S. J Nutr. 1996. PMID: 8642473 Review.
Cited by
-
NO donors and NO delivery methods for controlling biofilms in chronic lung infections.Appl Microbiol Biotechnol. 2021 May;105(10):3931-3954. doi: 10.1007/s00253-021-11274-2. Epub 2021 May 3. Appl Microbiol Biotechnol. 2021. PMID: 33937932 Free PMC article. Review.
-
Incidence and risk factors of early arterial blood flow stasis during first radioembolization of primary and secondary liver malignancy using resin microspheres: an initial single-center analysis.Eur Radiol. 2016 Aug;26(8):2779-89. doi: 10.1007/s00330-015-4076-6. Epub 2015 Nov 11. Eur Radiol. 2016. PMID: 26560720
-
Evaluation of the delivered activity of yttrium-90 resin microspheres using sterile water and 5 % glucose during administration.EJNMMI Res. 2015 Dec;5(1):54. doi: 10.1186/s13550-015-0133-z. Epub 2015 Oct 13. EJNMMI Res. 2015. PMID: 26463848 Free PMC article.
-
Design, characterization, and first-in-human study of the vascular actions of a novel biased apelin receptor agonist.Hypertension. 2015 Apr;65(4):834-40. doi: 10.1161/HYPERTENSIONAHA.114.05099. Epub 2015 Feb 23. Hypertension. 2015. PMID: 25712721 Free PMC article.
-
Recent developments in nitric oxide donor drugs.Br J Pharmacol. 2007 Jun;151(3):305-21. doi: 10.1038/sj.bjp.0707224. Epub 2007 Apr 2. Br J Pharmacol. 2007. PMID: 17401442 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources