PROJECT SUMMARY/ABSTRACT - Interaction of Dietary Potassium with High Dietary Sodium on the Vasculature of Humans Cardiovascular disease remains a major Public Health problem in the U.S. and is the result of sub-clinical diseases such as atherosclerosis and high blood pressure (BP). Several dietary factors have been implicated as risk factors. Indeed, it is well known that excess sodium consumption can increase BP while consumption of potassium has been shown to have BP lowering properties. While the role of these two nutrients on BP is widely accepted, their impact on the vasculature has received less attention. Vascular endothelial dysfunction, characterized by impaired dilation is an important non-traditional risk factor for atherosclerosis. Data in animal models suggest that salt loading, independent of changes in BP, results in vascular endothelial dysfunction while evidence is mounting that potassium may be beneficial to vascular health. Potential mechanisms responsible for sodium induced vascular dysfunction include overproduction of reactive oxygen species and stiffening of endothelial cells resulting in reduced nitric oxide (NO) production/bioavailability. Potassium has been suggested to have antioxidant capabilities that may counteract the effects of high sodium and has been shown to soften cultured endothelial cells stiffened from high sodium. Our central hypothesis is that sodium directly affects the vasculature and simultaneous consumption of potassium can ameliorate the detrimental effects of sodium by reducing oxidative stress and cell stiffness, thereby preserving NO. In this COBRE subproject, we propose to use a 21-day controlled feeding study to compare the effects of a high sodium diet (300 mmol) combined with either a high (120 mmol) or moderate (65 mmol) amount of potassium on 2 levels of the vasculature, conduit and microvasculature. These experiments will be performed in salt-resistant adults to study the vascular effects alone, independent of changes in BP. 24-hour ambulatory BP and urine collections during each diet condition will permit the individual assessment of salt sensitivity of BP. Brachial artery flow- mediated dilation will be used to assess conduit endothelial-dependent dilation and cutaneous vasodilation in response to local heating using laser Doppler flowmetry coupled with intradermal microdialysis will be used to assess microvascular function in the forearm. Arterial stiffness will be assessed by carotid-femoral pulse wave velocity and wave reflection by aortic augmentation index. A venous scraping of endothelial cells will be collected for assessment of oxidative stress and cell stiffness. We expect to demonstrate that high potassium protects the endothelium from the deleterious effects of high sodium by reducing oxidative stress and cell stiffness. These studies are novel in that they will be the first to critically evaluate the role of potassium on vascular function independent of BP and employ a comprehensive assessment of vascular function (conduit artery endothelial function, microvascular function, arterial stiffness, and endothelial cells from human subjects) to study the effect of a high potassium diet in the presence of high sodium. Further, the data collected from this proposal would allow for a larger exploration of this topic through a R01.