Endothelial dysfunction is a potential target for (pharmaceutical) intervention of several systemic pathological conditions. We investigated the feasibility of the EndoPAT to evaluate acute changes in endothelial function with repeated noninvasive measurements and assessed its discriminating power in different populations. Endothelial function was stable over a longer period of time in renally impaired patients (coefficient of variation 13%). Endothelial function in renally impaired and type 2 diabetic patients was not decreased compared to healthy volunteers ( and , resp., versus , ). The EndoPAT did not detect an effect of robust interventions on endothelial function in healthy volunteers (glucose load: change from baseline , 95% confidence interval ？0.44 to 0.60; smoking: change from baseline , 95% confidence interval ？0.47 to 1.46). This suggests that at present the EndoPAT might not be suitable to assess (changes in) endothelial function in early-phase clinical pharmacology studies. Endothelial function as measured by the EndoPAT could be physiologically different from endothelial function as measured by conventional techniques. This should be investigated carefully before the EndoPAT can be considered a useful tool in drug development or clinical practice. 1. Introduction Endothelial dysfunction is an early predictor of cardiovascular disease [1–3], and might be the causal pathological mechanism of a variety of metabolic diseases, also referred to as the common soil hypothesis [4]. Endothelial function has been shown to be impaired in patients with coronary artery disease, type II diabetes mellitus, hypertension, obesity, renal failure, and hypercholesterolemia [5–9]. It is conceivable that improvement of endothelial function will be an important target in the treatment of these conditions. Therefore, availability of methodology that can be used to reliably assess the effects of (pharmacological) treatments on endothelial function is of critical importance. Endothelial dysfunction is commonly described as the inability of the artery to sufficiently dilate in response to an appropriate endothelial stimulus. It can be assessed by measurement of the arterial pulse wave at a finger artery or by the measurement of flow-mediated dilation (FMD) of the brachial artery after occlusion of the blood flow. Although the exact mechanisms causing FMD are not entirely known, the main mechanism inducing FMD is thought to be an increase in shear stress, leading to the release of nitric oxide from endothelial cells which causes blood vessel dilation [10]. Currently,
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