Salty Subjects: Unpacking Racial Differences in Salt-Sensitive Hypertension

Abstract

Purpose of review: To review underlying mechanisms and environmental factors that may influence racial disparities in the development of salt-sensitive blood pressure.

Recent findings: Our group and others have observed racial differences in diet and hydration, which may influence salt sensitivity. Dietary salt elicits negative alterations to the gut microbiota and immune system, which may increase hypertension risk, but little is known regarding potential racial differences in these physiological responses. Antioxidant supplementation and exercise offset vascular dysfunction following dietary salt, including in Black adults. Furthermore, recent work proposes the role of racial differences in exposure to social determinants of health, and differences in health behaviors that may influence risk of salt sensitivity. Physiological and environmental factors contribute to the mechanisms that manifest in racial differences in salt-sensitive blood pressure. Using this information, additional work is needed to develop strategies that can attenuate racial disparities in salt-sensitive blood pressure.

Keywords: Blood pressure; Cardiorenal function; Gut microbiota; Health behaviors; Racial health disparities; Social determinants of health.

Figure 1.. The effects of dietary salt on endothelial function.

High dietary salt increases oxidative stress and inflammation in endothelial cells, and suppresses angiotensin II, which decreases superoxide dismutase (SOD) expression. SOD catalyzes the conversion of superoxide (O₂⁻) to hydrogen peroxide (H₂O₂) which promotes vasodilation. Endothelial nitric oxide synthase (eNOS) produces nitric oxide (NO), a potent vasodilator. High dietary salt promotes vascular dysfunction by increasing NADPH oxidase (NOX) expression, which produce reactive oxygen species and promotes conversion of NO to peroxynitrite (ONOO⁻) resulting in less vasodilation.

Figure 2.. High dietary salt acts on epithelial Na+ channel (ENaC) channels in immune cells and the kidney.

(A): High salt acts on the immune system by promoting a pro-inflammatory response. Specifically, salt increases epithelial Na⁺ channel (ENaC) activity on antigen presenting cells (APCs) which increases reactive oxygen species (ROS) production and production of cytokines such as interleukins (IL) IL-6, IL-23, and IL-1β. Furthermore, the APCs activate T cells which also promote systemic inflammation, including in the kidney and vasculature, contributing to hypertension. (B): The epithelial Na⁺ channel (ENaC) is a transport protein located in the distal nephron of the kidney and is responsible for regulating urinary sodium excretion. Aldosterone and serum and glucocorticoid-regulated kinase 1 (SGK1) promote ENaC activity. A normal response to high salt is suppression of aldosterone but there may be an aberrant response in the context of salt sensitivity.

Figure 3.. The association between dietary salt, the gut microbiome, and salt sensitivity.

High dietary salt increases Firmicutes/Bacteroidetes ratio and decreases short-chain fatty acid (SCFA) production in the large intestine. SCFAs absorbed by the intestinal epithelial cells can bind to G-protein-coupled receptors (GPR) which decreases BP, or olfactory receptors (Olfr) which oppose reductions blood pressure. In contrast, dietary fiber can lead to favorable changes in the gut microbiome.

Figure 4.. Overview of contributing factors to salt-sensitive blood pressure.

Physiological mechanisms (e.g., suppressed RAAS and reduced vascular function), social determinants of health (e.g., living in more disadvantaged neighborhoods and having lower socioeconomic position), and health behaviors (e.g., dietary potassium) combine to manifest in documented racial disparities in salt-sensitive blood pressure.