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

Background: Reduced nitric oxide bioavailability caused by endothelial dysf unction or damage is a contributory factor in the initiation and progressio n of a number of cardiovascular diseases. Delivery of exogenous nitric oxid e is an attractive therapeutic option, but current agents lack selectivity for areas of endothelial damage. We tested the hypothesis that a novel nitr ic oxide donor drug, N-(S-nitroso-N-acetylpenicillamine)-2-amino-2-deo 1,3, 4,6-tetra-O-acetyl-beta-glucopyranose [RIG200], which has selective effects in endothelium-denuded isolated arteries in vitro, would exert similar eff ects in dorsal hand veins with experimentally damaged endothelium in vivo. Methods: Venodilator responses to sodium nitroprusside and RIG200 were comp ared 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 doubl e-blind study, subjects were randomly assigned to receive either sodium nit roprusside or RIG200 (infusions of 0.06 and 6 nmol/min into the hand vein) before and 2 days after 15 minutes of local venous irrigation with distille d water, Endothelial function was assessed in all subjects on both visits w ith use of the endothelium-dependent vasodilator acetylcholine (1 nmol/min) . Results: Irrigation of hand veins with distilled water abolished endotheliu m-dependent dilatation in response to acetylcholine in both study groups (n = 14) but did not affect the amplitude or duration of responses to the con ventional 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 vein s with damaged endothelium, a characteristic that might be exploited therap eutically to target nitric oxide delivery to damaged blood vessels.