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J Am Coll Cardiol, 2007; 49:1289-1295, doi:10.1016/j.jacc.2006.10.074 (Published online 9 March 2007).
© 2007 by the American College of Cardiology Foundation
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Once Daily Therapy With Isosorbide-5-Mononitrate Causes Endothelial Dysfunction in Humans

Evidence of a Free-Radical–Mediated Mechanism

George R. Thomas, PhD*, Jonathan M. DiFabio, MSc*, Tommaso Gori, MD, PhD2,{dagger} and John D. Parker, MD, FACC1,*,*

* Division of Cardiology, Department of Medicine, University Health Network and Mount Sinai Hospitals and the Department of Pharmacology, University of Toronto, Toronto, Canada
{dagger} Department of Internal, Cardiovascular and Geriatric Medicine, University of Siena, Siena, Italy.


Figure 1
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  		Figure 1 A Schematic Diagram of the IS-5-MN Study Protocol

(A) Diagram of the study protocol to determine the effects of a 7-day isosorbide-5-mononitrate (IS-5-MN) therapy on endothelial function. (B) Diagram of the study protocol to determine the effect of vitamin C (vit C) on IS-5-MN–induced changes in endothelial function. Ach = acetylcholine; BP = blood pressure; HR = heart rate; IS-5-MN = isosorbide-5-mononitrate; L-NMMA = N-monomethyl-L-arginine; ROS = reactive oxygen species.

 

Figure 2
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  		Figure 2 FBF Responses to Ach Infusion

p < 0.05 for the effect of treatment group, 2-way analysis of variance. Ach = acetylcholine; FBF = forearm blood flow; IS-5-MN = isosorbide-5-mononitrate; I/N = ratio of forearm blood flow, infused to noninfused arms.

 

Figure 3
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  		Figure 3 FBF Responses to L-NMMA Infusion

p < 0.05 for the effect of treatment group, 2-way analysis of variance. L-NMMA = N-monomethyl-L-arginine, other abbreviations as in Figure 2.

 

Figure 4
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  		Figure 4 FBF Responses to Ach and Vitamin C Infusion

p < 0.05 for the effect of vitamin C versus saline coinfusion, 2-way analysis of variance. Abbreviations as in Figure 2.

 




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