Kurzfassung

The therapeutic utility of the organic nitrates was first described more than a century ago and the acute administration of sublingual nitroglycerin (GTN) to treat episodes of symptomatic angina remains a therapeutic standard around the world. More recently, there has been documentation that the sustained administration of organic nitrates is not only associated with tolerance but also the development of unexpected adverse vascular effects. In both animal and human models it has been...The therapeutic utility of the organic nitrates was first described more than a century ago and the acute administration of sublingual nitroglycerin (GTN) to treat episodes of symptomatic angina remains a therapeutic standard around the world. More recently, there has been documentation that the sustained administration of organic nitrates is not only associated with tolerance but also the development of unexpected adverse vascular effects. In both animal and human models it has been documented that the sustained use of nitrates is associated with the development of increased vascular free radical production, abnormalities in the function of endothelial nitric oxide synthase and severe abnormalities in endothelial function.
Paradoxically, recent observations have documented that short-term exposure to organic nitrates can protect the myocardium from later episodes of ischemia. Multiple animal studies have documented that short-term exposure to nitroglycerin creates a pharmacologically induced response that is similar to that observed with ischemic preconditioning. The current application attempts to verify that the short-term application of organic nitrates can have protective, ‘preconditioning’ effects. The mechanism of this phenomenon will be explored and studies will determine the ability of nitrates to induce pharmacologic preconditioning in both the vasculature and the myocardium. The clinical relevance of these observations will also be tested, determining whether repeated (daily) short-term exposure is associated with sustained protective effects.
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