Mg<sup>2+</sup> modulates membrane lipids in vascular smooth muscle: a link to atherogenesis

Morrill, Gene A.; Gupta, Raj K.; Kostellow, Adele B.; Ma, Gui-Ying; Zhang, Amin; Altura, Bella T.; Altura, Burton M.

doi:10.1016/s0014-5793(97)00420-1

Cited by 73 publications

(61 citation statements)

References 33 publications

(54 reference statements)

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“…4 Thus, Mg affects the pivotal cardiac functions, including cardiac contraction, 5 beating rhythm, 5,6 vasomotor control, 4,[7][8][9][10] and proliferation of smooth muscle cells in vessels. 9,11 Mg deficiency contributes to the pathogenesis of several cardiovascular diseases, eg, hypertension, 12 vasospastic angina, 13 ventricular arrhythmia, 14 and mitral valve prolapse. 15 Recently, Fiset et al 16 reported a high incidence of sudden death in Mg-deficient rats, and this result is consistent with epidemiological reports of a high incidence of sudden death in areas with low levels of Mg in drinking water 17 and also with clinical reports that hypomagnesemia is frequently observed in patients with heart failure in whom sudden death occurs.…”

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confidence: 99%

Effect of Magnesium Deficiency on Autonomic Circulatory Regulation in Conscious Rats

et al. 1999

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Abstract-A close relationship between magnesium and cardiovascular function has been reported; however, the effect of magnesium deficiency on autonomic cardiovascular regulation has not been clarified. We investigated the effect of magnesium deficiency on the autonomic regulation of oscillations of the R-R interval, arterial blood pressure (BP), and renal sympathetic nerve activity (RSNA) by using the maximum entropy method in conscious rats. Its effect on baroreflex control of RSNA and heart rate were also investigated with a logistic function curve. Mean BP in magnesium-deficient rats was higher than that in control rats (meanϮSE, 114.0Ϯ4.3 versus 101.6Ϯ3.4 mm Hg; PϽ0.05), and urinary excretion of catecholamine was increased by 2.4-fold. The fraction of low-frequency oscillation of RSNA was reduced (31.7Ϯ0.9% versus 36.2Ϯ1.5%, PϽ0.05) and the correlation between low-frequency oscillations of BP and RSNA was weakened in magnesium-deficient rats. There was no difference in high-frequency oscillation of the R-R interval, which is related to vagal tone, whereas sympathetic tone became dominant (square root of low-frequency/high-frequency ratio of R-R interval, 1.00Ϯ0.05 versus 0.67Ϯ0.05, PϽ0.0001) in magnesium-deficient rats. The maximal gain in the BP-RSNA relation tended to be reduced in magnesium-deficient rats (Ϫ7.7Ϯ1.1% versus Ϫ12.2Ϯ1.9%/mm Hg, Pϭ0.07); however, that in the BP-heart rate relation was increased (Ϫ8.1Ϯ0.7 versus Ϫ4.5Ϯ0.5 bpm/mm Hg, PϽ0.01). These results suggest that magnesium deficiency induces sympathetic excitation, which results in hypertension but attenuates the baroreflex-related response of sympathetic nerves, whereas magnesium deficiency enhances the sensitivity of the sinus node to autonomic regulation. (Hypertension. 1999;34:247-252.)

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confidence: 99%

Effect of Magnesium Deficiency on Autonomic Circulatory Regulation in Conscious Rats

et al. 1999

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“…Interestingly, increased membrane lipid peroxidation itself, as well as alterations of fatty acid composition and lipid-derived messengers, result from low-Mg environments. 30,31 In all of these systems, the antioxidant effects observed have been related to the SH group; enalapril was either not protective or even increased the damage. 32 Thus, although both Mg and SH compounds possess antioxidant properties, this is the first report in which a relation has been suggested between Mg itself and captopril-induced protection against metabolite depletion after ischemic stress.…”

Section: Discussionmentioning

confidence: 99%

“…The other 10 mL of blood from each patient sample was processed using 31 P-NMR techniques to measure erythrocyte Mg i levels before (basal, tϭ0 minutes) and 30, 60, and 120 minutes after the addition of various compounds: captopril (10 to 1000 mol/L), enalaprilat (10 to 100 mol/L), and other SH compounds, N-acetyl-L-cysteine (NAC, 300 mol/L), penicillamine (300 mol/L), and N-(2-mercaptopropionyl)-glycine (MPG, 300 mol/L). Doses of the other SH compounds tested were chosen to correspond to slightly more than the maximally effective Mg i -stimulating concentrations of captopril tested (see Results).…”

Section: P-nmr Analysis Of Mg Imentioning

confidence: 99%

Protective Effects of Captopril Against Ischemic Stress

1999

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Abstract-Magnesium (Mg) deficiency enhances tissue sensitivity to ischemic damage, an effect reversed not only by Mg, but also by sulfhydryl (SH)-containing compounds. We therefore created an in vitro model of red blood cell ischemia to investigate whether the protective effects of these compounds might be related to effects on intracellular free Mg (Mg i ) content. 31 P-nuclear magnetic resonance (NMR) spectroscopy was used to measure the high-energy metabolites ATP and 2,3-diphosphoglycerate (DPG) and Mg i and inorganic phosphate (P i ) levels in erythrocytes before and for 6 hours after progressive oxygen depletion in the presence or absence of SH-compounds, including captopril, N-acetyl-L-cysteine (NAC), penicillamine, and N-(2-mercaptopropionyl)-glycine (MPG). Under basal aerobic conditions, captopril increased Mg i in a dose-and time-dependent fashion (174.5Ϯ5.3 to 217.1Ϯ5.1 mol/L, PϽ0.05 at 100 mol/L, 60 minutes). The SH compounds NAC, penicillamine, and MPG but not the non-SH compound enalaprilat also significantly raised Mg i in erythrocytes (PϽ0.05). With oxygen deprivation, a consistent decrease occurred in both ATP and 2,3-DPG levels associated with a rise in P i and in the P i /2,3-DPG ratio used as an index of high-energy metabolite depletion. Captopril, compared with control, retarded the rise in P i and reduced the P i /2,3-DPG ratio (PϽ0.008 and PϽ0.025 at 4 and 6 hours, respectively). Furthermore, the higher the initial Mg i and the greater the captopril-induced rise in Mg i , the greater the metabolite-protective effect (rϭ0.799 and rϭ0.823, respectively; PϽ0.01 for both). Altogether, the data suggest that Mg influences the cellular response to ischemia and that the ability of SH compounds such as captopril to ameliorate ischemic injury may at least in part be attributable to the ability of such compounds to increase cytosolic free Mg levels.

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“…11). ]o with or without 75 uM scyphostatin (SigmaAldrich) for 18 h. We extracted the lipids in the cells as we have detailed elsewhere (54,55). The ceramide was next converted into ceramide-1-[ 32 P]phosphate by Escherichia coli DAG kinase, and the lipids were separated on high-performance TLC plates as described elsewhere (16,58).…”

Section: Influence Of An Inhibitor (Fumonisin B1) Of Cs On the De Novomentioning

confidence: 99%

“…As early as 15 years ago, using cerebral and peripheral vascular smooth muscle cells (VSMCs) in primary cultures, it was demonstrated that variation in free extracellular Mg 2ϩ concentration ([Mg 2ϩ ] o ) causes sustained alterations in membrane phospholipids and second messengers as well as activation of several signal transcription molecules, identical to those mentioned above (13,54,55). Such paradigms, using variations in Mg 2ϩ , also cause membrane oxidation, truncation of membrane fatty acids, and the activation of apoptotic pathways (i.e., caspase-3, apoptotic protease activation factor-1, and release of mitochondrial cytochrome c) concomitant with the significant activation of neutral sphingomyelinase (N-SMase) and alterations in membrane sphingomyelin (SM), leading to the release of ceramides in cultured VSMCs (14 -16, 68).…”

mentioning

confidence: 94%

Short-term magnesium deficiency upregulates ceramide synthase in cardiovascular tissues and cells: cross-talk among cytokines, Mg²⁺, NF-κB, and de novo ceramide

Altura

Shah²,

Shah³

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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BT. Short-term magnesium deficiency upregulates ceramide synthase in cardiovascular tissues and cells: crosstalk among cytokines, Mg 2ϩ , NF-B, and de novo ceramide. Am J Physiol Heart Circ Physiol 302: H319 -H332, 2012. First published October 7, 2011 doi:10.1152/ajpheart.00453.2011.-The present study tested the hypotheses that 1) short-term dietary deficiency (MgD) of magnesium (21 days) would result in the upregulation of ceramide synthase (CS) in left ventricular (LV), right ventricular, atrial, and aortic smooth muscle, as well as induce a synthesis/release of select cytokines and chemokines into the LV and aortic smooth muscle and serum; 2) exposure of primary cultured vascular smooth muscle cells (VSMCs) to low extracellular Mg concentration would lead to the synthesis/release of select cytokines/chemokines, activation of N-SMase, and the de novo synthesis of ceramide; and 3) inhibition of CS by fumonisin B1 (FB1) or inhibition of neutral sphingomyelinase (N-SMase) by scyphostatin (SCY) in VSMCs exposed to low Mg would result in reductions in the levels of the cytokines/chemokines and lowered levels of ceramide concomitant with inhibition of NF-B activation. The data indicated that shortterm MgD (10% normal dietary intake) resulted in the upregulation of CS in ventricular, atrial, and aortic smooth muscles coupled to the synthesis/release of 12 different cytokines/chemokines, as well as activation of NF-B in the LV and aortic smooth muscle and sera; even very low levels of water-borne Mg (e.g., 15 mg·l Ϫ1 ·day Ϫ1 ) either prevented or ameliorated the upregulation and synthesis of the cytokines/chemokines. Our experiments also showed that VSMCs exposed to low extracellular Mg resulted in the synthesis of 5 different cytokines and chemokines concomitant with synthesis/release of ceramide. However, inhibition of the synthesis and release of ceramide by either FB1 or SCY attenuated, markedly , the generation of ceramide, release of the cytokines/chemokines, and activation of NF-B (as measured by activated p65 and cRel). cardiac muscle; vascular muscle; p65; cRel; neutral sphingomyelinase; water-borne magnesium IMPROPER NUTRITION, HIGH CHOLESTEROL intake, and fatty diets are known to promote lipid deposition and accelerate growth and transformation of smooth muscle cells (SMCs) in the vascular wall (20,40,57). Over the past five decades, an accumulation of epidemiological and experimental data have indicated that a reduction in the dietary intake of Mg, as well as low Mg content in drinking water, is a risk factor for the development of hypertension, atherosclerosis, vasospasm, sudden cardiac death, stroke, and inflammatory conditions by ill-defined mechanisms (e.g., see Refs. 1,[4][5][6][17][18][19][27][28][29]35,38,46,48,49,63,64,65,67,72). Hypermagnesemic diets have been shown to ameliorate hypertension and atherogenesis (4,5,7,8,18,23,67). At present, the average dietary intake of Mg has declined from ϳ450 -485 mg/day in 1900 to ϳ185-235 mg/ day for large segments of the North American population (4, 30, ...

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Mg²⁺ modulates membrane lipids in vascular smooth muscle: a link to atherogenesis

Abstract: Epidemiological studies associate low dietary magnesium intake with an increased incidence of ischémie heart disease and sudden cardiac death. We have used proton-magnetic resonance (

Cited by 73 publications

References 33 publications

Effect of Magnesium Deficiency on Autonomic Circulatory Regulation in Conscious Rats

Effect of Magnesium Deficiency on Autonomic Circulatory Regulation in Conscious Rats

Protective Effects of Captopril Against Ischemic Stress

Short-term magnesium deficiency upregulates ceramide synthase in cardiovascular tissues and cells: cross-talk among cytokines, Mg²⁺, NF-κB, and de novo ceramide

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Mg2+ modulates membrane lipids in vascular smooth muscle: a link to atherogenesis

Abstract: Epidemiological studies associate low dietary magnesium intake with an increased incidence of ischémie heart disease and sudden cardiac death. We have used proton-magnetic resonance (

Cited by 73 publications

References 33 publications

Effect of Magnesium Deficiency on Autonomic Circulatory Regulation in Conscious Rats

Effect of Magnesium Deficiency on Autonomic Circulatory Regulation in Conscious Rats

Protective Effects of Captopril Against Ischemic Stress

Short-term magnesium deficiency upregulates ceramide synthase in cardiovascular tissues and cells: cross-talk among cytokines, Mg2+, NF-κB, and de novo ceramide

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Mg²⁺ modulates membrane lipids in vascular smooth muscle: a link to atherogenesis

Short-term magnesium deficiency upregulates ceramide synthase in cardiovascular tissues and cells: cross-talk among cytokines, Mg²⁺, NF-κB, and de novo ceramide