The role of dietary magnesium deficiency in inflammatory hypertension

Frontiers in Physiology

Physiology

Sydney Jamison¹  Daniel Bain²  Tracey Lam³  Evan C. Ray³  Linh Huynh³  Ritam Patel³  Ashley Pitzer Mutchler⁴  Annet Kirabo⁴ 

[1] Meharry Medical College Nashville, Nashville, TN, United States;University of Pittsburgh Department of Geology, Pittsburgh, PA, United States;University of Pittsburgh Department of Medicine, Renal-Electrolyte Division, Pittsburgh, PA, United States;Vanderbilt University Department of Medicine, Division of Clinical Pharmacology, Nashville, TN, United States;

关键词: magnesium;    hypertension;    isolevuglandins;    NLRP3;    dendritic cells;    blood pressure;    IL-1 beta;    inflammasome;   

DOI  :  10.3389/fphys.2023.1167904

 received in 2023-02-17, accepted in 2023-05-10,  发布年份 2023

来源: Frontiers

【 摘 要 】

Nearly 30% of adults consume less than the estimated average daily requirement of magnesium (Mg2+), and commonly used medications, such as diuretics, promote Mg2+ deficiency. Higher serum Mg2+ levels, increased dietary Mg2+ in-take, and Mg2+ supplementation are each associated with lower blood pressure, suggesting that Mg2+-deficiency contributes to the pathogenesis of hypertension. Antigen-presenting cells, such as monocytes and dendritic cells, are well-known to be involved in the pathogenesis of hypertension. In these cells, processes implicated as necessary for increased blood pressure include activation of the NLRP3 inflammasome, IL-1β production, and oxidative modification of fatty acids such as arachidonic acid, forming isolevuglandins (IsoLGs). We hypothesized that increased blood pressure in response to dietary Mg2+-depletion leads to increased NLRP3, IL-1β, and IsoLG production in antigen presenting cells. We found that a Mg2+-depleted diet (0.01% Mg2+ diet) increased blood pressure in mice compared to mice fed a 0.08% Mg2+ diet. Mg2+-depleted mice did not exhibit an increase in total body fluid, as measured by quantitative magnetic resonance. Plasma IL-1β concentrations were increased (0.13 ± 0.02 pg/mL vs. 0.04 ± 0.02 pg/mL). Using flow cytometry, we observed increased NLRP3 and IL-1β expression in antigen-presenting cells from spleen, kidney, and aorta. We also observed increased IsoLG production in antigen-presenting cells from these organs. Primary culture of CD11c+ dendritic cells confirmed that low extracellular Mg2+ exerts a direct effect on these cells, stimulating IL-1β and IL-18 production. The present findings show that NLRP3 inflammasome activation and IsoLG-adduct formation are stimulated when dietary Mg2+ is depleted. Interventions and increased dietary Mg2+ consumption may prove beneficial in decreasing the prevalence of hypertension and cardiovascular disease.

【 授权许可】

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Copyright © 2023 Pitzer Mutchler, Huynh, Patel, Lam, Bain, Jamison, Kirabo and Ray.