Physiological Mechanisms of Dietary Salt Sensing in the Brain, Kidney, and Gastrointestinal Tract

Abstract

Excess dietary salt (NaCl) intake is strongly correlated with cardiovascular disease and is a major contributing factor to the pathogenesis of hypertension. NaCl-sensitive hypertension is a multisystem disorder that involves renal dysfunction, vascular abnormalities, and neurogenically-mediated increases in peripheral resistance. Despite a major research focus on organ systems and these effector mechanisms causing NaCl-induced increases in arterial blood pressure, relatively less research has been directed at elucidating how NaCl is sensed by various tissues to elicit these downstream effects. The purpose of this review is to discuss how the brain, kidney, and gastrointestinal tract sense NaCl including key cell types, the role of NaCl versus osmolality, and the underlying molecular and electrochemical mechanisms.

Brain Pathways in Blood Pressure Regulation

“…8,9 However, central infusion of hypertonic NaCl but not mannitol increases SNA and ABP. 8,9 Moreover, subpopulations of these neurons are more sensitive to NaCl versus osmolality. These differences highlight the mechanisms and subpopulations of OVLT and SFO neurons regulating SNA versus body fluid homeostasis are notably different.…”

“…SFO and OVLT contain neurons that are intrinsically osmosensitive and depend on an N-terminal variant of the transient receptor potential vanilloid-1 channel. 8,9 However, central infusion of hypertonic NaCl but not mannitol increases SNA and ABP. 8,9 Moreover, subpopulations of these neurons are more sensitive to NaCl versus osmolality.…”

“…The OVLT and SFO can detect changes in hormones (angiotensin II, leptin, insulin), osmolality and extracellular NaCl concentrations, and cytokines through ion channels and receptors expressed on various cell types. 8,9 In turn, these neurons increase sympathetic outflow through polysynaptic connections through the PVH and RVLM (Figure). The OVLT and SFO can profoundly affect body fluid homeostasis (thirst, salt appetite, vasopressin secretion) but also contribute to most experimental models of hypertension including angiotensin II, deoxycorticosterone acetate plus salt, Dahl salt-sensitive, and renovascular hypertension.…”

“…Several mechanisms are postulated to mediate NaCl sensing in these structures and include amiloride-sensitive channels, NaX and acid-sensing ion channels, and stretch-inactivated cation channels. 8,9…”

“…The OVLT and SFO can profoundly affect body fluid homeostasis (thirst, salt appetite, vasopressin secretion) but also contribute to most experimental models of hypertension including angiotensin II, deoxycorticosterone acetate plus salt, Dahl salt-sensitive, and renovascular hypertension. 8,9…”