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(Circulation. 2005;111:721-723.)
© 2005 American Heart Association, Inc.

Editorial

Sildenafil and Endothelial Dysfunction in Humans

Garrett J. Gross, PhD

From the Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee.

Correspondence to Dr Garrett J. Gross, Dept of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226. E-mail ggross@mcw.edu

Key Words: Editorials • phosphodiesterase inhibitors • endothelium • potassium channels, inwardly rectifying • humans

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Although it is well established that ischemic preconditioning (IPC) and pharmacological preconditioning (PPC) protect cardiac myocytes against reversible and irreversible injury and the genesis of cardiac arrhythmias¹ in all animal species and humans, the effect of IPC and PPC on endothelial dysfunction has been less thoroughly studied. In this regard, the first article to clearly establish that IPC can protect endothelium against injury was published by DeFily and Chilian in 1993.² They demonstrated in dogs that IPC preserved the endothelial-mediated coronary dilator responses to 2 endothelial-dependent vasodilators, serotonin and acetylcholine, in the absence of any damage to the smooth muscle cells mediating the dilator response. From a mechanistic standpoint, it has also been known since 1992³ that adenosine triphosphate (ATP)-sensitive potassium channels (K_ATP channels) are an integral part of both acute and delayed IPC against myocardial infarction in animals and man.⁴ Subsequently, Katnik and Adams⁵ demonstrated that an ATP-sensitive potassium channel was present in rabbit endothelium that was inhibited by the K_ATP channel antagonists tolbutamide and glibenclamide. That endothelial K_ATP channels may be involved as a trigger in IPC to protect isolated guinea pig hearts against endothelial dysfunction was demonstrated recently by Beresewicz et al.⁶ These authors showed that the opening of mitochondrial K_ATP channels by IPC or diazoxide protected the endothelium by reducing the burst of reactive oxygen species, particularly the superoxide anion, which occurs at reperfusion.⁶ Thus, strong evidence in animal models indicates the presence of a K_ATP channel in endothelial cells and suggests that its activation resulting . . . [Full Text of this Article]

Related Article:

Sildenafil Prevents Endothelial Dysfunction Induced by Ischemia and Reperfusion via Opening of Adenosine Triphosphate–Sensitive Potassium Channels: A Human In Vivo Study

Tommaso Gori, Silvia Sicuro, Saverio Dragoni, Giovanni Donati, Sandro Forconi, and John D. Parker
Circulation 2005 111: 742-746. [Abstract] [Full Text]

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