Magnesium nitrate attenuates blood pressure rise in SHR rats.

The administration of magnesium supplements and nitrates/nitrites decreases arterial blood pressure and attenuates the development of hypertension-induced complications. This study was performed to examine the effects of treatment with magnesium nitrate on the development of hypertension and its complications in spontaneously hypertensive (SHR) rats. Male SHR rats with persistent hypertension at the age of 12-13 weeks were allocated to two groups according to their arterial blood pressure. Rats from the control group received purified water, while the experimental animals from the second group received magnesium nitrate dissolved in purified water at a dose of 50 mg/kg. After four weeks of treatment, blood pressure was measured, the anatomical and functional parameters of the heart were recorded using an ultrasonograph, vascular reactivity was assayed in organ bath experiments and the cardioprotective effects of magnesium nitrate administration was assayed in an ex vivo experimental heart infarction model. Treatment with magnesium nitrate significantly increased the nitrate concentration in the plasma (from 62 ± 8 µmol/l to 111 ± 8 µmol/L), and attenuated the increase in the arterial blood pressure. In the control and magnesium nitrate groups, the blood pressure rose by 21 ± 3 mmHg and 6 ± 4 mmHg, respectively. The administration of magnesium nitrate had no effect on the altered vasoreactivity, heart function or the size of the heart infarction. In conclusion, our results demonstrate that magnesium nitrate effectively attenuates the rise in arterial blood pressure. However, a longer period of administration or earlier onset of treatment might be needed to delay the development of complications due to hypertension.

Hypomagnesaemia.

Magnesium plays an important role in the body as a cofactor for DNA and protein synthesis, oxidative phosphorylation, neuromuscular excitability, enzyme activity and regulation of parathyroid hormone (PTH) secretion.1 The regulation of plasma magnesium concentration is balanced by intestinal absorption and renal excretion. Hypomagnesaemia (variously defined but taken here as plasma magnesium<0.7 mmol/L) may result from inadequate magnesium intake, increased gastrointestinal or renal loss or redistribution from extracellular to intracellular space. In addition, hypomagnesaemia has been associated with the use of a number of drugs and, in 2012, the Medicines and Healthcare products Regulatory Agency (MHRA) drew attention to the risk associated with prolonged use of proton pump inhibitors (PPIs).2 Here we review the causes and management of hypomagnesaemia.

Influence of the phosphodiesterase type 5 inhibitor, sildenafil, on antidepressant-like activity of magnesium in the forced swim test in mice.

Magnesium, which acts as an antagonist of N-methyl-D-aspartate (NMDA) subtype of glutamate receptors, exerts antidepressant-like activity in animal models of depression. The present study was undertaken to elucidate the influence of sildenafil, a phosphodiesterase type 5 inhibitor, on the anti-immobility action of magnesium in the forced swim test in mice. Swim sessions were conducted by placing mice in glass cylinders filled with water for 6 min and the duration of the behavioral immobility during the last 4 min of the test was evaluated. Locomotor activity was measured with photoresistor actimeters. Serum and brain magnesium levels were assayed spectrophotometrically. Magnesium at a dose of 30 mg/kg, i.p. significantly decreased the immobility time while sildenafil (5, 10 and 20 mg/kg, i.p.) in a dose-dependent manner reduced the antidepressant-like activity of magnesium. The co-administration of magnesium with sildenafil at the highest dose entirely abolished the antidepressant-like effect of magnesium and caused a statistically significant increase in immobility duration as compared to the control group. Combination of magnesium with sildenafil resulted in a potent reduction (80%) of locomotor activity and pharmacokinetic studies showed a significant increase of magnesium concentration in serum (as compared to magnesium treatment alone) without changes within brain tissue in mice treated with magnesium and sildenafil. When given alone, sildenafil caused a significant increase in magnesium levels in both serum and brain. Our results indicate that a simultaneous treatment with magnesium and sildenafil results in hypermagnesemia in laboratory animals. However, the mechanism underlying this effect remains elusive.

[Effects of magnesium supplementation on calcium and magnesium levels, and redox homeostasis in normolipidemic and food-induced hyperlipidemic rats]. / Magnéziumpótlás hatása a kalcium- és magnéziumszintekre, valamint a redox-homeosztázisra normolipidaemiás és alimentárisan eloidézett hyperlipidaemiás patkányokban.

UNLABELLED: Magnesium supplementation is quite popular because of intention of health and healthy lifestyle. However, there is no information on the metabolic effects of magnesium supplementation in healthy people and in different diseases. AIMS: Authors examined the effects of magnesium-malate on calcium, magnesium levels, and antioxidant parameters in normolipidemic and hyperlipidemic rats. METHODS: Male Wistar rats (n = 40; 150-200 g) were divided into 4 groups (control, control-treated, hyperlipidemic, hyperlipidemic-treated). Rats in the control and control-treated groups were fed with normal diet, while hyperlipidemic and hyperlipidemic-treated groups were fed with fat rich diet (2% cholesterol, 20% sunflower oil, 0.5% cholic acid). After the 9-day-long diet the following parameters were measured: routine laboratory parameters with automatic analysator, metal content using ICP-OES, and redox-parameters using spectrophotometric and luminometric methods. RESULTS: Magnesium-malate failed to produce significant changes in the measured parameters in control animals in most cases. Magnesium-malate decreased significantly serum glucose concentration, alkaline phosphatase and amylase activities in the hyperlipidemic group. Significantly low induced chemiluminescent activity was measured in the plasma and erythrocytes of hyperlipidemic group. The magnesium supplementation did not increase significantly magnesium concentration in different organs although the calcium/magnesium concentration ratio was decreased. CONCLUSIONS: In control animals there was no significant change in the measured parameters in most cases after dietary supplementation with a large amount of magnesium for a short period of time, but magnesium supplementation affected the metal homeostasis, routine laboratory parameters and redox system in hyperlipidemic animals. Although several changes were favorable, it should be emphasized that magnesium supplementation must be applied watchfully particularly in metabolic diseases.

Serum and dietary magnesium and risk of ischemic stroke: the Atherosclerosis Risk in Communities Study.

The authors sought to examine the relation between serum or dietary magnesium and the incidence of ischemic stroke among blacks and whites. Between 1987 and 1989, 14,221 men and women aged 45-64 years took part in the first examination of the Atherosclerosis Risk in Communities Study cohort. The incidence of stroke was ascertained from hospital records. Higher serum magnesium levels were associated with lower prevalence of hypertension and diabetes mellitus at baseline. During the 15-year follow-up, 577 ischemic strokes occurred. Serum magnesium was inversely associated with ischemic stroke incidence. The age-, sex-, and race-adjusted rate ratios of ischemic stroke for those with serum magnesium levels of or=1.8 mEq/L were 1.0, 0.78 (95% confidence interval (CI): 0.62, 0.96), 0.70 (95% CI: 0.56, 0.88), and 0.75 (95% CI: 0.59, 0.95) (P(trend) = 0.005). After adjustment for hypertension and diabetes, the rate ratios were attenuated to nonsignificant levels. Dietary magnesium intake was marginally inversely associated with the incidence of ischemic stroke (P(trend) = 0.09). Low serum magnesium levels could be associated with increased risk of ischemic stroke, in part, via effects on hypertension and diabetes.

Magnesium metabolism in health and disease.

Magnesium (Mg) is the main intracellular divalent cation, and under basal conditions the small intestine absorbs 30-50% of its intake. Normal serum Mg ranges between 1.7-2.3 mg/dl (0.75-0.95 mmol/l), at any age. Even though eighty percent of serum Mg is filtered at the glomerulus, only 3% of it is finally excreted in the urine. Altered magnesium balance can be found in diabetes mellitus, chronic renal failure, nephrolithiasis, osteoporosis, aplastic osteopathy, and heart and vascular disease. Three physiopathologic mechanisms can induce Mg deficiency: reduced intestinal absorption, increased urinary losses, or intracellular shift of this cation. Intravenous or oral Mg repletion is the main treatment, and potassium-sparing diuretics may also induce renal Mg saving. Because the kidney has a very large capacity for Mg excretion, hypermagnesemia usually occurs in the setting of renal insufficiency and excessive Mg intake. Body excretion of Mg can be enhanced by use of saline diuresis, furosemide, or dialysis depending on the clinical situation.

[Osteopenia in children with juvenile idiopathic arthritis]. / Osteopenia la copiii cu artrita juvenila idiopatica.

UNLABELLED: The aim of the study was to evaluate the presence and etiopathogenesis of osteopenia in 41 children with Juvenile Idiopathic Arthritis (JIA). METHODS: Bone status was evaluated by quantitative ultrasound using a Sunlight Omnisense 7000s Ultrasound Bone Sonometer. Measurements were performed at the distal radius and midshaft tibia. Results were obtained as Speed of sound (SOS) and Z-score. We used standardised clinical evaluation (modified Giannini's criteria, CHAQ). ESR, Fibrinogen, serum calcium, magnesium, alkaline phosphatase, protein electrophoresis, 25-OH vitamin D (RIA) and urinary Hydroxyproline were obtained in all patients. Osteopenia was present in 15 (36.5%) patients. Statistical analysis was performed with SPSS 13.0. RESULTS: Age, sex, age at onset, disease duration, life standards and duration of corticotherapy and methotrexate treatment were not related to osteopenia in our study. The disease activity, evaluated by clinical criteria, ESR and Fibrinogen, was strongly associated with osteopenia (p<0.001). Nutritional status was an independent risk factor for osteopenia (p<0.001). Low serum calcium (p=0.034), magnesium (p=0.010), 25-OH vitamin D (p=0.091) and alkaline phosphatase (p=0.31) were more frequent in patients with osteopenia. Hydroxyproline was increased in all patients with osteopenia (p<0.001). CONCLUSIONS: Osteopenia was a frequent (36.5%) complication of JIA in our study. The disease activity and nutritional status were the most important risk factors for osteopenia. The increase of bone reabsorption was the main pathogenic mechanism of osteopenia in our study. Calcium and magnesium deficits were related to osteopenia. Decrease of bone synthesis was not associated with osteopenia in the present study.

Antepartum/postpartum depressive symptoms and serum zinc and magnesium levels.

In the present study, we investigated the relationship between depressive symptoms and serum zinc and magnesium level in antepartum and postpartum women. All women received standard vitamin, zinc and magnesium supplementation. Sixty-six pregnant women in the Czerwiakowski Hospital in Kraków were assessed for prepartum depressive symptoms using the Beck Depression Inventory (BDI). Sixty-two and fifty-eight women were also assessed for postpartum depressive symptoms (using Edinburgh Postnatal Depression Rating Scale, EPDRS) at 3 and 30 days after delivery, respectively. Serum zinc and magnesium levels were also determined at these time points, however, the number of examined subjects were diminished. A significantly higher EPDRS score (by 45%), indicating severity of depressive symptoms, was found on the 3rd day after childbirth compared with the 30th postpartum day. Moreover, the early post-delivery period (3rd day) was characterized by a 24% lower serum zinc concentration than that found on the 30th day after childbirth. BDI scores assessed a month before childbirth revealed mild depressive symptoms, which was accompanied by a serum zinc concentration similar to that found on the 3rd day after delivery. No significant alterations were found in the magnesium levels between these time points. The present results demonstrated a relationship between severity of depressive symptoms and decreased serum zinc (but not magnesium) concentration in a very specific type of affective disorder, the postpartum depression.

Ionised and total serum magnesium in renal transplant patients.

BACKGROUND: Hypomagnesemia in renal transplant patients is almost always documented through total serum values (MgT), but it has recently become user-friendly to assay the biologically active, ionised fraction (Mg++). We verified the prevalence of true ionised magnesemia and the correspondence between total and ionised Mg assays in our transplanted patients, taking into account renal Mg excretion and the possible role of other reputed factors of hypomagnesemia (cyclosporine, secondary hyperparathyroidism and acid-base balance). METHODS: Thirty-eight transplanted patients (25M/13F, aged 41 +/- 11 years) and 38 age and sex matched controls were enrolled. Blood chemistries included: ionised Mg and Ca, total Mg and Ca, phosphate, creatinine, albumin, bicarbonate, alkaline phosphatase, parathyroid hormone and, in patients, cyclosporine (CyA). A 24-h urine collection (for Ca and Mg) and a fasting spot sample (for pH, Mg, Ca, phosphate, creatinine) were also obtained. RESULTS: Patients with mild renal failure (creatinine: Cr=1.75 +/- 0.83 mg/dL), mild persistent secondary hyperparathyroidism and almost normal tubular acidification capacity had MgT lower than controls (0.76 +/- 0.08 vs 0.82 +/- 0.08 mmol/L; p<0.002), with 10 cases (26%) of total hypomagnesemia. Mg++ was also significantly low (0.51 +/- 0.08 vs 0.53 +/- 0.05 mmol/L; p<0.03), but there were only four cases (10%) of true ionised hypomagnesemia. MgT and Mg++, although correlated (with a low r value: =0.49; p<0.001), showed poor correspondence in individual patients and MgT was not useful to identify cases of true ionised hypomagnesemia. Neither assay correlated with renal function. Daily urinary excretion of Mg was normal (3.5 +/- 1.3 vs 3.0 +/- 0.24 mmol/day; n.s.), with no case of definite hypomagnesuria. Fasting excretion fraction (EF) of Mg, calculated with both assays, was increased in approximately 60% of patients (EF(MgT) 4.9 +/- 2.6 vs 2.32 +/- 0.7%; p<0.0001; EF(Mg++) 7.74 +/- 4.9 vs 3.63 +/- 1.18%; p<0.0001) and positively correlated with serum Cr (r=0.62; p<0.0001 with EF(MgT); and r=0.467; p<0.005 with EF(Mg++) but not with CyA. Neither Mg assay correlated with serum CyA, calcium, phosphate, PTH or bicarbonate. CONCLUSIONS: In long term renal transplant patients not taking diuretics, the prevalence of true ionised hypomagnesemia is low. Renal insufficiency, typically associated with Mg retention, is the major cause of increased EF(Mg) and, as such, plays an antagonistic role to CyA and other factors of renal Mg wasting. Because MgT and Mg++ are not closely related, assay of the ionised fraction seems advisable in case of total hypomagnesemia. However, because diagnosis of depletion can hardly rely on serum assay alone, a fuller evaluation (urinary excretion and other clinical and biochemical signs of hypomagnesemia) is suggested before diagnosis is made.

Bioavailability and pharmacokinetics of magnesium after administration of magnesium salts to humans.

Therapeutically, magnesium salts represent an important class of compounds and exhibit various pharmacologic actions. Examples of magnesium salts are ionic magnesium and magnesium citrate in nephrolithiasis, magnesium salicylate in rheumatoid arthritis, magnesium hydroxide as an antacid as well as a cathartic, and magnesium mandelate as urinary antiseptic. Various anions attached to the cation magnesium, such as oxide, chloride, gluconate, and lactate, affect the delivery of the amounts of elemental magnesium to the target site and thereby produce different pharmacodynamic effects. This review examines the bioavailability and pharmacokinetics of various magnesium salts and correlates pharmacodynamic action with the structure-activity relationship.

[Efficacy and tolerance of a calcium-magnesium-aspartate solution in the treatment of hypocalcemic parturient paresis in cows]. / Zur Wirksamkeit und Verträglichkeit einer Kalzium-Magnesium-Aspartat-Lösung bei der Behandlung der hypokalzämischen Gebärparese des Rindes.

The systemic tolerance of a solution of calcium aspartate and magnesium aspartate was studied in 7 cows. Intravenously administered dosages of 500 ml per cow were well tolerated. A twofold increase of the serum calcium concentration was measured. In 2 cows which were treated with 1000 ml of the solution a threefold increased calcium concentration and heart arrhythmia were found. The clinical efficacy of the solution was demonstrated in a study with 44 hypocalcemic cows. A long lasting increase of the serum calcium as well as an enhanced phosphorus concentration were measurable. In conclusion, the calcium-magnesium-aspartate solution seems to be an efficacious and well tolerated alternative for the treatment of hypocalcemia in cows.

[Tocolytic treatment of pregnant women with threatened abortions and preterm labor in the second and third trimesters of pregnancy with magne B6 (a preliminary communication)]. / Tokolitichno lechenie pri bremenni sus zaplashvashti aborti i prezhdevremenni razhdaniia vuv vtoriia i tretiia trimestur na bremennostta s preparat "Magne B6" (predvaritelno suobshtenie).

The authors check the effect of the substitutional treatment of the pregnant patients with the uterine paints and contractions in the second and third months periods of the pregnancy with "Magne B6"--Sanofi. In the group of the examined patients the Mg deficiency that is the cause for these suffering has been established. After the substitutional treatment with "Magne B6" the described suffering disappeared and clinical-lab values of Mg in the serum and urine normalized.