Once Daily Therapy With Isosorbide-5-Mononitrate Causes Endothelial Dysfunction in HumansEvidence of a Free-Radical–Mediated Mechanism
George R. Thomas, PhD*,
Jonathan M. DiFabio, MSc*,
Tommaso Gori, MD, PhD and
John D. Parker, MD, FACC*,*
* Division of Cardiology, Department of Medicine, University Health Network and Mount Sinai Hospitals and the Department of Pharmacology, University of Toronto, Toronto, Canada
Department of Internal, Cardiovascular and Geriatric Medicine, University of Siena, Siena, Italy. Supported by a research donation from the Henry White Kinnear Foundation. Dr. Parker holds a Career Investigator Award from the Heart and Stroke Foundation of Ontario, Canada. Dr. Gori is the recipient of a grant from the Italian Ministry of Research
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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.
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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.
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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.
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