Magnesium Deficiency and Hypertension: Correlation Between Magnesium-Deficient Diets and Microcirculatory Changes in Situ

Altura, Burton M.; Altura, Bella T.; Gebrewold, Asefa; Ising, H; Günther, Th.

doi:10.1126/science.6701524

Cited by 353 publications

(155 citation statements)

References 31 publications

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“…4,5,7,19 -21 Mg 2ϩ also modulates neuronal activity 6,7 but the precise mechanisms are still unknown. In the present study, we showed an Mg 2ϩ effect on sympathetic tone both in in vivo and in vitro studies.…”

Section: Discussionmentioning

confidence: 99%

“…4,5 On the contrary, Mg 2ϩ deficiency results in a high catecholamine level, altered barofunction, and hypertension. 6,7 Sympathoactivation and catecholamine elevation induce tachycardia, glucose intolerance, and abnormal fat metabolism, as well as direct cardiotoxicity. 8,9 At the same time, recent clinical studies revealed that Mg 2ϩ protects brain from ischemic damages.…”

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confidence: 99%

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Magnesium Inhibits Norepinephrine Release by Blocking N-Type Calcium Channels at Peripheral Sympathetic Nerve Endings

et al. 2004

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Abstract-AlthoughMg 2ϩ contributes to blood pressure regulation partly in terms of vasodilator action, its sympatholytic effect may also play an important role to control blood pressure. Thus, in the present study, we investigated the effect of Mg 2ϩ on sympathetic tone and blood pressure. We studied its actions on the blood pressure response to hydralazine, a direct vasodilator, in conscious spontaneously hypertensive rats (SHRs), and to electrical stimulation in the pithed Sprague-Dawley rat; catecholamine release by peripheral sympathetic nerve endings; and the N-type MethodsFor a detailed Methods section, please see http://hyper.hypertensionaha.org.All protocols in this study were approved by the ethics committee of our institution, and rats were handled in our accredited facility in accordance with the institutional animal care policies of the University of Tokyo. All research protocols conformed to the guiding principles for animal experimentation as enunciated by the Ethics Committee on Animal Research of the University of Tokyo, Faculty of Medicine. Protocol 1: Sympatholytic Effect of Mg 2؉ and Blood Pressure Changes In VivoMale spontaneously hypertensive rats were used in this experiment. The rats were divided into 2 groups: Mg 2ϩ group (nϭ8) and a control group (nϭ7). In the Mg 2ϩ group, MgSO 4 (3ϫ10 Ϫ6 mol/kg body weight/min) was infused, and in the control group saline was infused. Responses to hydralazine (1, 3, and 6ϫ10Ϫ5 g/kg body weight) were observed. A 100 L blood sample was drawn before and after saline or MgSO 4 infusion to measure the serum Mg level. The nadir mean

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Magnesium Inhibits Norepinephrine Release by Blocking N-Type Calcium Channels at Peripheral Sympathetic Nerve Endings

et al. 2004

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Section: Magnesium (Mgmentioning

confidence: 99%

“…Mg 2ϩ deficiency results in small cell size and cell cycle arrest (11), as well as accelerated cell senescence (12), and intracellular Mg 2ϩ levels modulate the activity of many ion channels (13-18). In whole animals, hypomagnesemia results in hypocalcemia (19,20), and Mg 2ϩ deficiency has been correlated to hypertension (21,22 (42)(43)(44)46), has raised interest in putative Mg 2ϩ channels. TRPM6 mutations have been linked to the human genetic disease familial hypomagnesemia with secondary hypocalcemia (47,48).…”

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confidence: 99%

Mammalian MagT1 and TUSC3 are required for cellular magnesium uptake and vertebrate embryonic development

Zhou

Clapham²

2009

Proc. Natl. Acad. Sci. U.S.A.

176

184

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Magnesium (Mg [Mg 2ϩ ] is Ϸ0.5-1 mM (2-5). The majority of Mg 2ϩ is bound to the major building blocks of the cell, such as proteins, phospholipids, nucleic acids, and especially ATP (6). Serum [Mg 2ϩ ] is maintained in a relatively narrow range (1-2 mM) in mammals (7), only slightly higher than the intracellular free [Mg 2ϩ ], making the reversal potential for Mg 2ϩ close to zero. Thus, the electrochemical gradient for Mg 2ϩ is normally into the cell due to the negative plasma membrane potential. Compared to [Ca 2ϩ ], free [Mg 2ϩ ] in the cytosol fluctuates much less dramatically with extracellular stimuli (8). Nevertheless, Mg 2ϩ plays a fundamentally important role in cellular processes. Mg 2ϩ serves as a major cofactor of ATP; Ͼ90% of cellular ATP is Mg-ATP (9). Therefore, it is not surprising that cell metabolism and many enzymatic activities are affected by Mg 2ϩ homeostasis (10). Mg 2ϩ deficiency results in small cell size and cell cycle arrest (11), as well as accelerated cell senescence (12), and intracellular Mg 2ϩ levels modulate the activity of many ion channels (13-18). In whole animals, hypomagnesemia results in hypocalcemia (19,20), and Mg 2ϩ deficiency has been correlated to hypertension (21,22 (42)(43)(44)46), has raised interest in putative Mg 2ϩ channels. TRPM6 mutations have been linked to the human genetic disease familial hypomagnesemia with secondary hypocalcemia (47,48). TRPM7 knockout in DT-40 avian lymphocytes exhibited a Mg 2ϩ deficiency phenotype and growth arrest (49). However, detailed studies of [Mg 2ϩ ] in tissues of TRPM7 Ϫ/Ϫ mice show that these channels play little direct role in Mg 2ϩ homeostasis (50). The extremely low inward conductance of the TRPM6/7 channels rather suggests that the affects of permeant Mg 2ϩ are confined to the immediate vicinity of the channel.In this report, we took advantage of the growth arrest phenotype of the S. cerevisiae Mg 2ϩ transporter mutant alr1⌬, and performed a complementary screen to search for potential human genes that could rescue the phenotype. We found that MagT1, and its homolog, TUSC3, support the growth of alr1⌬ yeast without Mg 2ϩ supplementation. We show that both genes are required for mammalian cellular Mg 2ϩ uptake and are crucial for zebrafish embryonic development. ResultsMagT1 and TUSC3 Complement the Yeast ALR1 Mg 2؉ Transporter.

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“…Intracellular free magnesium concentration is low in clinical and experimental hypertension (Resnick et al, 1984;Ng et al, 1992). Magnesium deficiency in rats induces hypertension, reduces blood vessel lumen (Altura et al, 1984) and increases plasma endothelin concentration (Weglicki et al, 1992). Magnesium infusion induces vasodilatation (Ji et al, 1983), and recent studies report that it strongly inhibits endothelin-1-induced vasoconstriction (Kemp et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Endothelin‐1‐induced contraction in isolated aortae from normotensive and DOCA‐salt hypertensive rats: effect of magnesium

Laurant

Berthelot

1996

British J Pharmacology

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1 The contractile responses to endothelin-1 and the effect on these of various magnesium concentrations, were studied in isolated aortic rings from normotensive Sprague-Dawley rats and deoxycorticosterone acetate-salt (DOCA-salt) hypertensive rats. 2 Contractions induced by endothelin-1 were smaller in endothelium-denuded aortae from DOCA-salt hypertensive rats than in those from normotensive rats. The absence of calcium in the medium attenuated endothelin-l-induced contractions of aortae from both normotensive and DOCA-salt rats, but the contraction was greater in aortae from DOCA-salt hypertensive rats. Ryanodine (which inhibits the release of intracellular calcium) inhibited endothelin-l-induced contractions in aortae from DOCAsalt hypertensive rats to a greater extent than in aortae from normotensive rats. 3 A high extracellular magnesium concentration (4.8 mM) attenuated endothelin-l-induced contractions in tissues from DOCA-salt hypertensive rats but not in tissues from normotensive rats. In the absence of calcium, a high concentration of magnesium attenuated endothelin-l-induced contraction in aortae from both normotensive and hypertensive rats. In the presence of ryanodine, a high concentration of magnesium did not modify the contraction in preparations from either strain. 4 Absence of magnesium attenuated endothelin-l-induced contractions in aortae from both normotensive and DOCA-salt hypertensive rats. In the absence of calcium, removal of magnesium totally inhibited endothelin-l-induced contraction in tissues from normotensive rats but had no effect in those from hypertensive rats. In the presence of ryanodine, the lack of magnesium inhibited endothelin-1-induced contractions in aortae from DOCA-salt hypertensive rats but increased the sensitivity to endothelin-1 of aortae from normotensive rats. 5 The presence of endothelium did not modify the effect of high magnesium on endothelin-l-induced contractions in aortae from normotensive and DOCA-salt hypertensive rats. Conversely, the attenuating effect of magnesium removal on endothelin-l-induced contractions did not occur when endothelium was present.6 In conclusion, endothelin-l-induced contraction was blunted in aortae from DOCA-salt hypertensive rats. The blunted response was related to altered calcium utilization during contraction. Changes in extracellular magnesium concentration differentially alter endothelin-l-induced contraction in aortae from normotensive and hypertensive rats, possibly by interfering with calcium utilization during contraction. Magnesium may be required for the contractile response to endothelin-1 and increasing magnesium may limit the vascular effects of endothelin-1 in blood vessels from DOCA-salt hypertensive rats.

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Magnesium Deficiency and Hypertension: Correlation Between Magnesium-Deficient Diets and Microcirculatory Changes in Situ

Cited by 353 publications

References 31 publications

Magnesium Inhibits Norepinephrine Release by Blocking N-Type Calcium Channels at Peripheral Sympathetic Nerve Endings

Magnesium Inhibits Norepinephrine Release by Blocking N-Type Calcium Channels at Peripheral Sympathetic Nerve Endings

Mammalian MagT1 and TUSC3 are required for cellular magnesium uptake and vertebrate embryonic development

Endothelin‐1‐induced contraction in isolated aortae from normotensive and DOCA‐salt hypertensive rats: effect of magnesium

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