Salt-Sensitive Hypertension and Vascular Dysfunction

The salt-sensitivity of blood pressure (SSBP) affects 50% of hypertensive individuals and ∼25% of normotensive individuals (increasing their hypertension risk) and is a risk factor for cardiovascular disease independent of blood pressure (BP). When consuming a high-salt (HS) diet ∼90% of U.S. consume excess salt), individuals with the SSBP develop salt-sensitive hypertension (SSH). Historically, the SSBP is thought to be mainly determined by neural and renal mechanisms. In salt-sensitive (SS) individuals, the brain fails to suppress sympathetic outflow in response to a HS diet and renal sodium handling is impaired, contributing to SSH. During HS-intake salt-resistant (SR) individuals suppress sympathetic outflow maintain sodium balance, and normotension. Recently, this classic theory was challenged due to its lack of consideration for vascular dysfunction as a contributing mechanism for the SSBP. Growing evidence shows a HS diet induces vascular dysfunction, including endothelial dysfunction and arterial stiffening, that may contribute to SSH. Furthermore, the endothelial glycocalyx is proposed to impact how the vasculature responds to a HS diet, the so-called ‘vascular salt-sensitivity’. In this review, we summarize recent evidence on the pathophysiology of SSH with an emphasis on mechanisms regarding vascular dysfunction. HS diet-induced vascular dysfunction occurs regardless of changes in BP but may be exacerbated in SS phenotypes. Future studies are warranted to further delineate the causes for SSH and vascular dysfunction through stratification of SS/SR and normotensive/hypertensive to provide mechanistic insights into the relationship between the SSBP and vascular salt-sensitivity to promote precision medicine for cardiovascular disease management in those populations.