Published online before print September 19, 2005, doi: 10.1161/01.HYP.0000185191.86908.a7
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(Hypertension. 2005;46:647.)
© 2005 American Heart Association, Inc.
Editorial Commentaries |
Nicorandil
The Drug That Keeps on Giving
From the Cleveland Clinic Foundation, Lerner Research Institute, Department of Cell Biology/NC10, Ohio.
Correspondence to John C. Barbato, Cleveland Clinic Foundation, Lerner Research Institute, Department of Cell Biology/NC10, 9500 Euclid Ave, Cleveland, OH 44195. E-mail barbatj@ccf.org
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Nicorandil is a nicotinamide nitrate used as an antianginal agent. It has two modes of action. First, by opening adenosine triphosphate–dependent potassium channels, nicorandil increases transmembrane potassium conductance and relaxes peripheral and coronary arterioles. Second, with its nitrate moiety, nicorandil increases intracellular concentrations of cGMP, resulting in peripheral vein and coronary artery dilation. Thus, because of its ability to dilate arteries and veins, nicorandil maximizes coronary flow while concomitantly reducing myocardial work through reductions in afterload. For these reasons, nicorandil has been successful in managing angina and hypertension. However, growing evidence suggests that this drug provides additional benefits that reach beyond its original therapeutic indications.
Recently, the Impact of Nicorandil in Angina (IONA) study demonstrated significant improvement in outcomes in patients with angina when comparing a composite end point of morbidity and mortality attributable to coronary heart disease, nonfatal myocardial infarction, and unplanned hospital admission for chest pain.1 The consensus regarding the success of nicorandil in IONA purports an association between cardiac preservation and mitochondrial adenosine triphosphate–dependent potassium (KATP) channel activation.1 In light of what is already known about KATP channels, this is a germane conclusion, specifically, with regard to the pivotal role KATP channels play in cardiac preconditioning and the beneficial actions that are associated with KATP channel activation.
For more than a decade, the connection between KATP channels and cardiac preconditioning has been known. Numerous studies pertaining to ischemic preconditioning, a phenomenon whereby intermittent bouts of transient ischemia render the heart more resistant to future ischemic insults,2
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Hypertension 2005 46: 719-724.