Adaptations of Arterial Function and Endothelial Glycocalyx to High-Sodium Diet in Mice

INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of death in the United States and excess sodium intake is a major contributor for CVD. A central feature of CVD is arterial dysfunction (i.e., elevated systolic blood pressure [BP], aortic stiffening, and endothelial dysfunction). Previously, we have shown that 12 weeks of high-sodium (HS) diet induces these arterial dysfunction phenotypes in genetically diverse, outbred UM-HET3 mice. Arterial dysfunction is suggested to be preceded by a deteriorated endothelial glycocalyx, which is a negatively charged gel-like structure bound to the luminal endothelium. Glycocalyx is hypothesized to buffer sodium cation in the blood stream, but excess blood sodium can in turn deteriorate endothelial glycocalyx. Indeed, we have previously shown that 12 weeks of HS diet deteriorates glycocalyx barrier function and decreases its thickness. However, the time course of HS diet-induced arterial dysfunction and glycocalyx deterioration remains elusive. Dietary sodium reduction has a well-established BP-lowering effect, but the reduction in BP is usually marginal. Other studies have also shown that HS-diet induced elevation in BP appears to be largely irreversible after HS diet withdrawal. It remains unknown whether the irreversibility exists in HS diet-induced arterial dysfunction and glycocalyx deterioration in UM-HET3 mice. In addition, we have previously shown that glycocalyx-targeted supplementation Endocalyx fully reverses age-related arterial dysfunction and glycocalyx deterioration in old mice, but the treatment effect of Endocalyx on HS diet-induced arterial dysfunction and glycocalyx deterioration remains unknown.