EDITORIAL COMMENT Does Nitroglycerin Therapy Hit the Endothelium?*

Nitrates are still widely used in the management of coronary artery disease (CAD) in patients with stable and unstable angina, acute myocardial infarction and congestive heart failure. The therapeutic efficacy of these nitrates is due to peripheral venous and arterial dilation that results in decreased myocardial oxygen consumption. Nitrates also dilate large coronary arteries and collaterals while having minimal or no effect on arteriolar tone. It is assumed that nitroglycerin (NTG) induces vasorelaxation by releasing the vasoactive principle nitric oxide (NO) via an enzymatic biotransformation step. Nitric oxide, an endothelium-derived relaxing factor, activates the target enzyme soluble guanylyl cyclase (sGC) and increases tissue levels of the second messenger cyclic guanosine monophosphate (cGMP). Cyclic GMP in turn activates a cGMP-dependent protein kinase which has been shown to mediate vasorelaxation via