The role of dietary magnesium deficiency in inflammatory hypertension

Abstract

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.

Magnesium Is a Vital Ion in the Body—It Is Time to Consider Its Supplementation on a Routine Basis

“…In our narrative review, we wanted to highlight the key points of this relationship and the contradiction that magnesium supplementation, a simple and inexpensive maneuver, is not included in daily practice. According to some authors, at least 30% of the adult population does not consume the daily magnesium requirement through their diet [ 8 ]. It is vital to note that insufficient magnesium intake can lead to a range of health problems, including muscle cramps, fatigue, and even cardiovascular disease.…”

“…According to some authors, at least 30% of the adult population does not consume the daily magnesium requirement through their diet [ 8 ].…”

Magnesium in hypertension: mechanisms and clinical implications

“…However, in C56Bl/6J mice, a Mg 2+ -restricted diet did increase blood pressure raising-effects of sympathetic stimulation. In mice of the sv129 background, dietary Mg 2+ restriction increased blood pressure by 21 days until sacrifice at 5 weeks ( Pitzer Mutchler et al, 2023 ). Intravenous Mg 2+ infusion in rats attenuates increases in blood pressure resulting from angiotensin II ( Atarashi et al, 1990 ) or sympathetic nerve stimulation ( Shimosawa et al, 2004 ).…”

“…Although mechanisms discussed above suggest that systemic Mg 2+ depletion should promote tubular reabsorption of Na + , modulation of extracellular fluid volume by Mg 2+ has not been described. In a study examining the impact of dietary Mg 2+ depletion upon blood pressure and fluid volume in mice, although a Mg 2+ -deficient diet increased blood pressure, it did not increase body fluid content, as measured using quantitative magnetic resonance ( Pitzer Mutchler et al, 2023 ). However, Na + overload promotes hypertension via mechanisms that may be Mg 2+ -sensitive, discussed below.…”

“…Oral Mg 2+ supplementation in humans suppresses circulating C-reactive protein ( Mazidi et al, 2018 ). In mice experiencing hypertension in response to dietary Mg 2+ restriction, circulating IL-1β levels increase ( Pitzer Mutchler et al, 2023 ). NLRP3 and IsoLG positivity in splenic and renal dendritic cells increase to levels comparable to a high Na + diet.…”