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.

Keywords: NaCl; angiotensin II; cardiovascular diseases; renal; sodium.

Figure 1.. OVLT Neurons Detect Changes in Extracellular NaCl Concentrations.

A, In vitro electrophysiological recording in current clamp showing concentration-dependent excitation of rat OVLT neuron to hypertonic NaCl . B, In vivo single-unit recording of rat OVLT neuron in which intracerebroventricular infusion of 0.5M NaCl (2.5uL over 5 min) increased neuronal discharge and ABP . C, fMRI images in the horizontal (a) and sagittal (b) planes of the human brain during IV infusion of hypertonic NaCl (0.5M NaCl at 11.4mL/kg/hr over 25 min) (Copyright 2003 National Academy of Sciences U.S.A.).

Figure 2.. Hypertonic NaCl Evokes a Greater Response in OVLT Neurons than Hyperosmolality.

A, In vitro whole-cell recording of OVLT neuron demonstrating hypertonic NaCl evokes a greater response versus equi-osmotic mannitol . B, In vivo single-unit recording of OVLT neuron to illustrate intracarotid infusion of hypertonic NaCl (50uL over 15 s) evokes a concentration-dependent increase in neuronal discharge and ABP. Intracarotid infusion of equi-osmotic sorbitol increased discharge and ABP but the magnitude was smaller . C, Intracerebroventricular infusion of 0.5M NaCl (2.5uL per 5 min) increased OVLT neurons discharge and ABP in rats. Equi-osmotic infusion of sorbitol produced a smaller increase in OVLT discharge without any changes in ABP ().

Figure 3.. Traditional and novel salt sensing mechanisms and functions of MD cells.

ERK1/2: extracellular signal regulated kinase 1 and 2; Cox2: cyclooxygenase 2; Nos1: nitric oxide synthase type 1; PGE2: prostaglandin E2; NO: nitric oxide; SGLT1: sodium-glucose cotransporter 1; Pappa2: pregnancy-associated plasma protein a2.