Salt-Sensitivity of Blood Pressure and Insulin Resistance

Abstract

Salt sensitivity of blood pressure (SSBP) is an independent risk factor for cardiovascular morbidity and mortality that is seen in both hypertensive and normotensive populations. Insulin resistance (IR) strongly correlates with SSBP and affects nearly 50% of salt sensitive people. While the precise mechanism by which IR and SSBP relate remains elusive, several common pathways are involved in the genesis of both processes, including vascular dysfunction and immune activation. Vascular dysfunction associated with insulin resistance is characterized by loss of nitric oxide (NO)-mediated vasodilation and heightened endothelin-1 induced vasoconstriction, as well as capillary rarefaction. It manifests with increased blood pressure (BP) in salt sensitive murine models. Another common denominator in the pathogenesis of insulin resistance, hypertension, and salt sensitivity (SS) is immune activation involving pro-inflammatory cytokines like tumor necrosis factor (TNF)-α, IL-1β, and IL-6. In the last decade, a new understanding of interstitial sodium storage in tissues such as skin and muscle has revolutionized traditional concepts of body sodium handling and pathogenesis of SS. We have shown that interstitial Na+ can trigger a T cell mediated inflammatory response through formation of isolevuglandin protein adducts in antigen presenting cells (APCs), and that this response is implicated in salt sensitive hypertension. The peroxisome proliferator-activated receptor γ (PPARγ) is a transcription factor that modulates both insulin sensitivity and BP. PPARγ agonists increase insulin sensitivity and ameliorate salt sensitivity, whereas deficiency of PPARγ results in severe insulin resistance and hypertension. These findings suggest that PPARγ plays a role in the common pathogenesis of insulin sensitivity and salt sensitivity, perhaps via effects on the immune system and vascular function. The goal of this review is to discuss those mechanisms that may play a role in both SSBP and in insulin resistance.

Dendritic Cell Epithelial Sodium Channel in Inflammation, Salt-Sensitive Hypertension, and Kidney Damage

“…The concentration of this stored Na + has been correlated with higher blood pressure 30,31 . While the relationship between tissue Na + storage and salt sensitivity is still unknown, differences in the regulation of this storage has been hypothesized to affect salt sensitivity 32,33 .…”

Immune Cell Activation in Obesity and Cardiovascular Disease

“…Salt sensitivity and insulin resistance share characteristics such as vascular dysfunction and immune activation stemming from CD8 + T cell stimulation. Impairment in PPARγ function under both of these conditions may link insulin resistance and hypertension driving changes in the adaptive immune system [ 59 ]. In response to high salt environments, T cells become pro-inflammatory and travel via the circulatory system to the brain, heart, and kidneys [ 60 ].…”

Insulin Resistance and High Blood Pressure: Mechanistic Insight on the Role of the Kidney

“…Demonstration that some hypertensive patients have a significant raise in blood pressure when they eat a diet containing high sodium led to the development of the concept of salt-sensitive hypertension [ 83 ]. Following the demonstration that elevated circulating insulin causes renal sodium retention, it was suggested that hyperinsulinemia resulting from insulin resistance might have a role in the mechanisms of salt sensitivity in hypertension [ 84 ]. Studies conducted in hypertensive patients have shown an association of salt sensitivity with hyperinsulinemia and insulin resistance that is independent of age, gender, and body mass [ 84 ].…”