Urinary Excretion Of Mg Research Articles

The plasma and urine mineral status of lambs offered diets of perennial wheat or annual wheat, with or without lucerne

The development of perennial wheat is proposed to increase resource-use efficiency and sustainability of crop production. Annual dual-purpose winter wheat and perennial wheat offer grazing potential, however they both have mineral imbalances due to excess forage K and deficient Na, which may lead to metabolic diseases such as hypocalcaemia and hypomagnesaemia. Notwithstanding a low forage Na concentration, it was hypothesised that the addition of forage lucerne (alfalfa), high in forage Ca and Mg, may overcome calcium and magnesium deficiencies of the wheat varieties. A pen feeding study was conducted using 10-month-old Poll Dorset × Merino ewe lambs (46.4 ± 1.8 kg) to test the effect on plasma and urine mineral status with the addition of lucerne to perennial wheat or annual wheat forage. The lambs (n = 48) were individually fed one of four diets, including perennial wheat (PW), annual wheat (W), perennial wheat + lucerne (alfalfa) (PW + L) or annual wheat + lucerne (W + L) and feed intake was calculated daily. Individual blood and urine sampling commenced on entry to the pens and were repeated at 7-day intervals for 3 further weeks. The addition of lucerne increased the dietary supply of Ca, Mg and Na and decreased K and P. When compared to W, PW offered more Ca, Mg, K, and less Na and P. There were mineral intake differences over time (P < 0.001) for all minerals. All diets offered high dietary cation anion difference (45.0 – 94.9), K: (Na + Mg) (7.3 – 12.8), K: Na (305 – 1137) ratios, while the addition of lucerne increased the Ca: P ratio and improved the K: (Mg + Ca) (Tetany index). Plasma Mg, Na, K and P declined significantly throughout the study, under all diets, to varying degrees. In Week 1, plasma Mg was significantly lower in PW lambs when compared to all other diets, but no further diet effects were observed thereafter. By contrast, plasma Ca increased throughout the study, but without dietary effects. The urinary excretion of Mg was higher with the addition of lucerne in the PW + L and W + L diets after 1-week, although this effect declined in subsequent weeks. The excretion of Ca, Na and P was very low in urine and decreased, while K excretion increased during the study. Taken together the results indicate that the greater dietary intake of Ca, Mg and Na due to the addition of lucerne was insufficient to overcome the primary mineral imbalance of high dietary K and low Na in the cereal forages. Furthermore, the addition of lucerne to the diet further decreased P intake and greatly increased the Ca: P ratio. Our calculations suggest lambs grazing any of the diets in the present study still required supplementation with Na and Mg, but the addition of lucerne alleviated the need for Ca supplementation. The need for supplementation with a source of dietary P requires further investigation.

Effects of distillers dried grains with solubles and forage dietary concentration in precision-fed dairy heifer diets: Mineral apparent absorption and retention

ABSTRACT Objective The objectives were to determine the effects of feeding different forage-to-concentrate ratios (F:C) and corn distillers dried grains with solubles (DDGS) inclusion rates on mineral apparent absorption (AAb) and retention in precision-fed dairy heifer rations. Materials and Methods A split plot design with F:C as whole plot [50:50 (LF) or 75:25 (HF)] and DDGS concentration as subplot (0, 7, 14 and 21%) was administered in a 4 × 4 Latin square using 8 ruminally cannulated Holstein heifers (12.5 ± 0.5 mo of age and 344 ± 15 kg of BW), and targeted an ADG of 800 g/d. Results and Discussion Mineral intake was affected by F:C and DDGS; there was a linear interaction in DMI. Fecal excretion of Mg, S, and Mn was greater for heifers fed HF diets, and fecal Ca, Mg, P, S, and Mn decreased linearly with increasing DDGS. Urinary excretion of Mg was greater for LF and decreased as DDGS increased. The AAb of Mg, S, and Mn was greater for LF. Linear and quadratic interactions between F:C and DGGS in AAb were observed for S and Mg, respectively. Retention of Mg was greater in LF; no differences were detected for Ca, K, Na, and S retention with F:C or DDGS. Linear interactions between F:C and DGGS were observed in the retention of Mg, P, and S. Linear and quadratic interactions in AAb for Mg and S, respectively, and a linear interaction for Mg, P, and S rentention demonstrate the importance of digestion kinetics when different F:C are used to evaluate dietary manipulations. Implications and Applications There was a linear reduction of Ca, Mg, P, S, and Mn fecal excretion in response to the linear reduction of DMI as DDGS were incorporated in diets. Heifers fed high forage diets had greater DMI and rate of passage resulting in small increases in Mg, S, and Mn excretion in feces. Absorption and retention of most minerals, notably Ca, K, Na, and P, were not affected by dietary levels of DDGS.

Essential trace elements in amyotrophic lateral sclerosis (ALS): Results in a population of a risk area of Italy.

Sardinian (Italy) island population has a uniquely high incidence of amyotrophic lateral sclerosis (ALS). Essential trace element levels in blood, hair, and urine of ALS Sardinian patients were investigated in search of valid biomarkers to recognize and predict ALS. Six elements (Ca, Cu, Fe, Mg, Se, and Zn) were measured in 34 patients compared to 30 age- and sex-matched healthy controls by a validated method. Levels of Ca and Cu in blood and of Se and Zn in hair were significantly higher in ALS than in controls, while urinary excretion of Mg and Se was significantly decreased. The selected cut-off concentrations for these biomarkers may distinguish patients with or without ALS with sufficient sensitivity and specificity. Many positive (as Se-Cu and Se-Zn) and negative associations (as Ca-Mg and Ca-Zn) between elements suggested that multiple metals involved in multiple mechanisms have a role in the ALS degeneration.

Daily Intake of Magnesium and its Relation to Urinary Excretion in Korean Healthy Adults Consuming Self-Selected Diets.

Magnesium (Mg) is an essential nutrient as a structural constituent of bone and regulator of >300 enzymes. However, studies on intake and urinary excretion of Mg are limited. The purpose of this study was to evaluate Mg intake and its relation to 24-h urinary excretion in healthy adults. Anthropometric measurements and dietary intake by the 24-h recall method were conducted in 80 adults aged 21-69 (average 44.3)years. Urine was collected for 24h on the day following the dietary survey. Dietary assessment and 24-h urine collection were repeated 3days later. Daily intake and urinary excretion of Mg were analyzed using Can-Pro and ICP-OES, respectively. The statistical analysis was conducted using SAS program. Mg intake of the subjects was 319±129mg/day for men and 277±94mg/day for women and the proportion of subjects who did not meet the estimated average requirement was 50 and 67.5% for men and women, respectively. Urinary Mg excretion was 30.3% of the daily Mg intake. Urinary Mg excretion was not significantly correlated with the daily Mg intake. Korean adults are not meeting the recommended intake of Mg, but its urinary excretion suggests homeostasis is not compromised.

Caveolin-1 Deficiency Inhibits the Basolateral K+ Channels in the Distal Convoluted Tubule and Impairs Renal K+ and Mg2+ Transport.

Kcnj10 encodes the inwardly rectifying K(+) channel Kir4.1 in the basolateral membrane of the distal convoluted tubule (DCT) and is activated by c-Src. However, the regulation and function of this K(+) channel are incompletely characterized. Here, patch-clamp experiments in Kcnj10-transfected HEK293 cells demonstrated that c-Src-induced stimulation of Kcnj10 requires coexpression of caveolin-1 (cav-1), and immunostaining showed expression of cav-1 in the basolateral membrane of parvalbumin-positive DCT. Patch-clamp experiments detected a 40-pS inwardly rectifying K(+) channel, a heterotetramer of Kir4.1/Kir5.1, in the basolateral membrane of the early DCT (DCT1) in both wild-type (WT) and cav-1-knockout (KO) mice. However, the activity of this basolateral 40-pS K(+) channel was lower in KO mice than in WT mice. Moreover, the K(+) reversal potential (an indication of membrane potential) was less negative in the DCT1 of KO mice than in the DCT1 of WT mice. Western blot analysis demonstrated that cav-1 deficiency decreased the expression of the Na(+)/Cl(-) cotransporter and Ste20-proline-alanine-rich kinase (SPAK) but increased the expression of epithelial Na(+) channel-α. Furthermore, the urinary excretion of Mg(2+) and K(+) was significantly higher in KO mice than in WT mice, and KO mice developed hypomagnesemia, hypocalcemia, and hypokalemia. We conclude that disruption of cav-1 decreases basolateral K(+) channel activity and depolarizes the cell membrane potential in the DCT1 at least in part by suppressing the stimulatory effect of c-Src on Kcnj10. Furthermore, the decrease in Kcnj10 and Na(+)/Cl(-) cotransporter expression induced by cav-1 deficiency may underlie the compromised renal transport of Mg(2+), Ca(2+), and K(+).

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Objectives To review the role of magnesium in pregnancy. Methods Analysis of published reports with emphasis on recent work on cellular mechanisms and magnesium responsive genes (MgRGs), plus controlled trials of magnesium (Mg) supplementation to prevent gestational hypertension. Results In a study on women with normal pregnancies, MgRGs were up regulated as compared to non-pregnant women, suggesting a higher Mg demand. They also had lower plasma levels of Mg and an increased urinary excretion of Mg. Systolic and diastolic blood pressure increases during pregnancy were related to the urinary excretion of Mg. Among women with PE, the expression of the MgRG SLC41A1 – a Na/Mg exchanger – was overexpressed in 54.2% of the placentas as compared to 9.5% in normal placentas. Brain and muscle levels of Mg were lower among women with PE. In three supplementation studies, Mg reduced the occurrence of gestational hypertension, particularly the diastolic blood pressure. Conclusions Data from genetic, cellular, and clinical studies support a conclusion that Mg plays an important role in pregnancy and that Mg deficiency could be a major factor for the pathogenesis in complicated pregnancies. It is unlikely that Mg is the sole agent involved and other nutritional factors are probably also of importance. Further studies are needed to assess the relationship with Mg and formulate requirements for intervention programs. Disclosures R. Rylander: None.

The claudin-16 channel gene is transcriptionally inhibited by 1,25-dihydroxyvitaminD.

What is the central question of this study? In the kidney, the bulk of the filtered Mg(2+) is reabsorbed in the thick ascending limb by paracellular conductance, mediated by the tight junction protein, claudin-16, which is encoded by the gene CLDN16. The role of 1,25-dihydroxyvitamin D [1,25(OH)2 VitD] in renal Mg(2+) handling is unclear. We aimed to explore the molecular mechanisms underlying the effect of 1,25(OH)2 VitD on claudin-16-mediated Mg(2+) transport. What is the main finding and its importance? Paracellular, claudin-16-mediated Mg(2+) transport is transcriptionally repressed by 1,25(OH)2 VitD, probably via a Ca(2+)-sensing receptor-dependent mechanism. This renal effect of 1,25(OH)2 VitD may serve as an adaptive mechanism to the 1,25(OH)2 VitD-induced enteric hyperabsorption of dietary Mg(2+). Magnesium is reabsorbed in the thick ascending limb by paracellular conductance, mediated by the CLDN16-encoded tight junction protein, claudin-16. However, the role of 1,25-dihydroxyvitamin D [1,25(OH)2 VitD] in renal Mg(2+) handling is unclear. We have shown that Mg(2+) depletion increases and 1,25(OH)2 VitD inhibits CLDN16 transcription. We have now explored further the molecular mechanisms underlying the effect of 1,25(OH)2 VitD on claudin-16-mediated Mg(2+) transport. Adult mice received parenteral 1,25(OH)2 VitD or 1,25(OH)2 VitD combined with either high-Mg(2+) or low-Mg(2+) diets. Administration of 1,25(OH)2 VitD enhanced urinary excretion of Mg(2+) and Ca(2+). The 1,25(OH)2 VitD also increased renal Ca(2+)-sensing receptor (CaSR) mRNA and decreased renal claudin-16 and claudin-19 mRNA and claudin-16 protein, but did not affect renal claudin-2 mRNA. The 1,25(OH)2 VitD reversed the expected increase in claudin-16 mRNA in Mg(2+)-depleted animals. Comparably treated HEK 293 cells showed similar changes in claudin-16 mRNA, but 1,25(OH)2 VitD did not alter mRNA of the TRPM6 Mg(2+) channel. A luciferase reporter vector containing 2.5 kb of 5'-flanking DNA sequence from human CLDN16 (hCLDN16) was transfected into HEK 293 and OK cells. The hCLDN16 promoter activity was modestly decreased by 1,25(OH)2 VitD, but markedly inhibited in HEK 293 cells coexpressing CaSR. Coexpression in OK cells of dominant-negative CaSR completely abolished inhibition of hCLDN16 promoter activity by 1,25(OH)2 VitD. The 1,25(OH)2 VitD-induced decrease in hCLDN16 promoter activity was attenuated in Mg(2+)-depleted HEK 293 cells. In conclusion, 1,25(OH)2 VitD transcriptionally inhibits claudin-16 expression by a mechanism sensitive to CaSR and Mg(2+). This renal effect of 1,25(OH)2 VitD may serve as an adaptive response to the 1,25(OH)2 VitD-induced increase in intestinal Mg(2+) absorption.

Magnesium in pregnancy blood pressure and pre-eclampsia - A review.

Magnesium is an important cation present in more than 300 enzymes in the body. This review evaluates the information on magnesium and pregnancy. In normal pregnancies Mg responsive genes are upregulated, suggesting Mg deficiency. Blood pressure increase is related to the urinary excretion of Mg. In pregnancies complicated by preeclampsia the Mg homeostasis is different from normal pregnancies. Supplementation with Mg has shown beneficial effects on high blood pressure and infant conditions in some studies. Although several studies show important relationships between Mg homeostasis and pregnancy, particularly those with pre-eclampsia, further studies are needed to assess the relationship and formulate requirements for intervention programmes.

Non-Natriuretic Doses of Furosemide: Potential Use for Decreasing the Workload of the Renal Outer Medulla with Minimal Magnesium Wasting in the Rat

Background/Aims: Since furosemide (FS) inhibits active Na⁺ reabsorption by medullary thick ascending limb (mTAL) in the renal outer medulla, it may decrease its work during periods of low O₂ supply to deep in the renal outer medulla. This study was designed to demonstrate that there may be a dose of FS would reduce its metabolic work while preventing the excessive loss of magnesium (Mg²⁺). Mg²⁺ is important because the ATP needed to perform work must have bound Mg²⁺ to it. Methods: Rats were injected intraperitoneally with a range of doses of FS. The measured outcomes were urine flow rate and parameters of functions of the mTAL (i.e. urine and renal papillary osmolality and urinary excretion of Na⁺, Cl^-, K⁺ and Mg²⁺, and concentrations of Mg²⁺ in serum). Results: The urine flow rate increased significantly starting at 2.4 mg FS/kg. The renal papillary osmolality decreased at ≥0.4 mg FS/kg, and the large detectable natriuresis started at 1.6 mg FS/kg. At this latter dose, the urinary excretion of Mg²⁺ rose significantly. Conclusion: In rats, the non-natriuretic dose of FS may reduce the work of the mTAL. The earliest indicator of reduced work in the mTAL appears to be a decrease in urine osmolality rather than a rise in urine flow rate. Higher doses of FS should be avoided, as they induce high rates of Mg²⁺ excretion, which can deplete the body of this essential electrolyte.

Double gene deletion reveals lack of cooperation between claudin 11 and claudin 14 tight junction proteins

Members of the claudin family of proteins are the main components of tight junctions (TJs), the major selective barrier of the paracellular pathway between epithelial cells. The selectivity and specificity of TJ strands are determined by the type of claudins present. An understanding of the cooperation between different claudins in various tissues is thus important. To study the possible cooperation between claudin 11 and claudin 14, we have generated claudin 11/claudin 14 double-deficient mice, which exhibit a combination of the phenotypes found in each of the singly deficient mutants, including deafness, neurological deficits, and male sterility. These two claudins have distinct and partially overlapping expression patterns in the kidney. Claudin 11 is located in both the proximal and distal convoluted tubules, whereas claudin 14 occurs in both the thin descending and thick ascending limbs of the loop of Henle and in the proximal convoluted tubules. Although daily urinary excretion of Mg(++), and to a lesser extent of Ca(++), tends to be higher in claudin 11/claudin 14 double mutants, these changes do not reach statistical significance compared with wild-type animals. Thus, under normal conditions, co-deletion of claudin 11 and claudin 14 does not affect kidney function or ion balance. Our data demonstrate that, despite the importance of each of these claudins, there is probably no functional cooperation between them. Generation of additional mouse models in which different claudins are abolished should provide further insight into the complex interactions between claudin proteins in various physiological systems.

Dysregulation of renal sodium transporters in gentamicin-treated rats

We aimed to investigate the molecular mechanisms underlying the renal wasting of Na(+), K(+), Ca(2+), and Mg(2+) in gentamicin (GM)-treated rats. Male Wistar rats were injected with GM (40 or 80 mg/kg/day for 7 days, respectively; GM-40 or GM-80). The expression of NHE3, Na-K-ATPase, NKCC2, ROMK, NCC, alpha-, beta- and gamma-ENaC, and CaSR was examined in the kidney by immunoblotting and immunohistochemistry. Urinary fractional excretion of Na(+), K(+), Ca(2+), and Mg(2+) was increased and urinary concentration was decreased in both GM-40 and GM-80 rats. In cortex and outer stripe of outer medulla (cortex) in GM-80 rats, the expression of NHE3, Na-K-ATPase, and NKCC2 was decreased; NCC expression was unchanged; and CaSR was upregulated compared to controls. In the inner stripe of outer medulla (ISOM) in GM-80 rats, NKCC2 and Na-K-ATPase expression was decreased, whereas CaSR was upregulated, and NHE3 and ROMK expression remained unchanged. In GM-40 rats, NKCC2 expression was decreased in the cortex and ISOM, whereas NHE3, Na-K-ATPase, CaSR, ROMK, and NCC abundance was unchanged in both cortex and ISOM. Immunoperoxidase labeling confirmed decreased expression of NKCC2 in the thick ascending limb (TAL) in both GM-80- and GM-40-treated rats. Immunoblotting and immunohistochemical analysis revealed increased expression of alpha-, beta-, and gamma-ENaC in cortex in GM-80 rats, but not in GM-40 rats. These findings suggest that the decrease in NKCC2 in TAL seen in response to low-dose (40 mg/kg/day) gentamicin treatment may play an essential role for the increased urinary excretion of Mg(2+) and Ca(2+), and play a significant role for the development of the urinary concentrating defect, and increased urinary excretion of Na(+) and K(+). At high-dose gentamicin, both proximal and TAL sodium transporter downregulation is likely to contribute to this.

マグネシウム欠乏ラットのマグネシウム，カルシウム，リン利用に及ぼす飼料中マグネシウム添加の影響

The effect is investigated of dietary magnesium (Mg) supplementation on the Mg, calcium (Ca) and phosphorus (P) utilization in Mg-deficient rats. Three-week-old male Wistar rats were fed on either a control diet (control group) or Mg-deficient diet (Mg-deficient group) for 28 days. Half the rats in the Mg-deficient group were then changed from the Mg-deficient diet to the control diet (recovery group) for 14 days. The Mg-deficient group displayed a change in Mg, Ca and P utilization (balance study and serum level). After the diet had been changed, the apparent absorption of Mg, the urinary excretion of Mg and Ca, and the retention of Mg and P were significantly higher in the recovery group than in the Mg-deficient group. The urinary P excretion was also significantly lower in the recovery group than in the Mg-deficient group. The serum Mg and P levels were also significantly higher in the recovery group than in the Mg-deficient group after the diet had been changed, while the serum Ca level was significantly lower in the recovery group than in the Mg-deficient group. The results of this study suggest that the Mg-deficient diet induced changes in the Mg and P balance, and that the serum levels of Mg, Ca and P were restored by changing from the Mg-deficient diet to the control diet.

Magnesium and potassium homeostasis during cisplatin treatment

Administration of cisplatin causes changes in magnesium and potassium metabolism. The purpose of this study was to investigate day-to-day changes in renal and intestinal homeostasis of magnesium (Mg) and potassium (K) during repeated cisplatin treatments in rats to provide guidelines for human supplementation studies. Rats were housed in metabolic cages with access to a diet containing excess Mg and K. Treatment was administered once a week for 3 weeks and comprised either cisplatin 2.5 mg/kg body weight i.p or, as sham treatment, isotonic NaCl 2.5 ml/kg body weight i.p. Urine and feces were collected every 24 h. Blood samples for measurement of plasma Mg and K were obtained from a permanent arterial catheter prior to each treatment cycle and at the termination of the study. Cisplatin exerted a significant negative effect on total Mg balance. This effect was cumulative with repeated doses of cisplatin. The observed difference was mainly due to the difference in Mg balance between the treatment day and the following 2-3 days. The cumulated urinary excretion of Mg did not differ significantly between the two groups at the end of follow-up. A significant decrease was observed in cumulated intestinal absorption in treated rats compared to control rats at the end of follow-up. Lowered intestinal absorption accounted for 90% of the difference in total Mg balance between the two groups as compared to the renal loss. Cisplatin treatment also exerted a negative effect on total K balance, although the difference between cisplatin-treated and control rats was not significant at the end of follow-up. The Mg loss associated with cisplatin treatment was mainly the result of lowered intestinal absorption and not, as presently thought, the result of increased renal elimination. Instead, an increased renal reabsorption capacity was observed in response to decreased intestinal absorption. The study further showed that Mg and K metabolism are subject to predictable changes in intestinal absorption and renal excretion with each cisplatin treatment, and that knowledge of these changes can be used in planning supplementation. Thus, the experimental observations support intravenous supplementation on the day of treatment and 2-3 days after treatment followed by oral supplementation until the next treatment.

Apparent magnesium absorption in dry cows fed at 3 levels of potassium and 2 levels of magnesium intake.

In vitro experiments with isolated rumen epithelium have shown that the relationship between the ruminal K concentration and either the apical membrane potential difference or the mucosal-to-serosal Mg flux reach plateau values at high ruminal K concentrations. Hence, it may be hypothesized that the inhibitory effect of supplemental K on Mg absorption becomes smaller at high initial K intakes. To test our hypothesis, 6 ruminally fistulated, nonpregnant dry cows were fed 6 experimental diets in a 6 x 6 Latin square design with a 2 x 3 factorial arrangement of treatments. Four cows were of a Friesian-Holstein x Holstein-Friesian cross, and the 2 remaining cows were of a Meuse-Rhine-IJssel x Holstein-Friesian cross. The diets provided either 40.6 or 69.1 g of Mg per day and contained 20.7, 48.0, or 75.5 g of K per kilogram of dry matter. The dietary variables were obtained by mixing KHCO(3) and MgO into the basal concentrate. Absorption of Mg and the urinary Mg excretion was significantly decreased by supplemental K and significantly increased after the intake of supplemental Mg. In contrast to apparent Mg absorption, the urinary excretion of Mg was not affected by the dietary K x Mg interaction. Postfeeding ruminal K and Mg concentrations were increased with increasing K and Mg intakes. Postfeeding ruminal K concentrations and the urinary excretion of Mg showed a linear negative correlation; the slope was not significantly affected by Mg intake. Therefore, our hypothesis was rejected. Furthermore, these data indicate that supplemental Mg can effectively counteract the suppressant effect of K on Mg absorption in cows.

The effects of losartan and losartan/hydrochlorothiazide fixed combination on zinc and magnesium metabolism in patients with hypertension

Drug combinations with thiazides (TZD) are common in the treatment of hypertension. We have previously shown that treatment with ACE inhibitors increased urinary Zinc (Zn) excretion, while TZD enhance urinary Zn and magnesium (Mg) losses. The effects of angiotensin receptor blockers on Zn and Mg metabolism are unknown. Sixteen Caucasian hypertensives (10 men, age 51±3 years,(SEM), body mass index 31±2 kg/m2), received losartan (LOS) 50mg (Ocsaar, MSD) for 4 weeks and LOS 50mg+hydrochlorothiazide (HCT) 12.5mg (Ocsaar plus, MSD) for the next 4 weeks. Serum, peripheral blood mononuclears (PBMC) and 24-hour urinary Zn and Mg concentrations were determined at baseline, after LOS and after LOS+HCT treatments. LOS treatment significantly increased urinary Zn excretion (from 0.24±0.07 mcg/mg creatinine to 0.43±0.08 mcg/mg creatinine, p=0.01), and was associated with a significant decrease in PBMC Zn levels (from 13.8±0.8 mcg/mg protein to 12.4±0.8 mcg/mg protein, p=0.01). LOS+HCT further increased urinary Zn excretion (from 0.43±0.08 mcg/mg creatinine after LOS to 0.74±0.2 mcg/mg creatinine after LOS+HCT, p=0.04), but had no effect on PBMC Zn concentrations. Serum Zn concentrations remained unchanged after both treatments. Serum and PBMC Mg concentrations, and urinary excretion of Mg remained unchanged too. Treatment with LOS, induces increased urinary Zn excretion and Zn depletion in hypertensive patients. HCT has an additive effect. LOS and LOS+HCT had no effect on Mg metabolism. Clinical Pharmacology & Therapeutics (2004) 75, P12–P12; doi: 10.1016/j.clpt.2003.11.046

Effects of sulphate- and bicarbonate-rich mineral waters on net and fractional intestinal absorption and urinary excretion of magnesium in rats

Magnesium (Mg) intake is below the recommended daily allowances in many developed countries. Mg-rich mineral waters can provide significant amounts of energy-free Mg and thus help to meet Mg requirements. We assessed the effects of different Mg-rich mineral waters on overall intestinal Mg absorption and urinary Mg excretion in 40 rats split into four groups: one received distilled water, another a solution of MgCl(2) and the others two different mineral waters, sulphated water (Hépar) and carbonated water (Badoit) mixed with the diet and as drinking water, for four weeks. The rats were given 3 mg of (26)Mg orally and 0.5 mg of (25)Mg intravenously. They were placed in metabolic cages, and diet consumption, and faeces and urine excretion were monitored during the last four days of the experiment. The rats were then sacrificed and blood was sampled. Mg levels in the diet, faeces, urine and biological samples were measured by atomic absorption spectrometry. Mg stable isotope measurements were performed by ICP/MS. Mg-rich mineral waters significantly increased net intestinal absorption of Mg by more than 30%, but the proportions of both apparent and true intestinal absorption of Mg were similar in all four groups. Thus, net and fractional retention of Mg were similar in the three Mg-supplemented groups. In conclusion, both types of Mg-rich mineral waters studied similarly increased both absorption and urinary excretion of Mg with no positive effect on the overall retention of Mg, probably because the Mg status of the rats was already satisfactory.

Renal cortical calcification in syngeneic intact rats and those receiving an infrarenal thoracic aortic graft: possible etiological roles of endothelin, nitrate and minerals, and different preventive effects of long-term oral treatment with magnesium, citrate and alkali-containing preparations.

Renal cortical nephrocalcinosis (C-NC) is a rare disorder of uncertain etiology. Using highly inbred (syngeneic) male Lewis rats, we describe the spontaneous occurrence of histologically detectable C-NC in sham operated control rats (Sham; n=12), its aggravation following grafting of the ascending thoracic aorta from a donor rat to the infrarenal aorta of a recipient (ATx; n=12), and differences in C-NC inhibition after 12 weeks of oral administration of magnesium (Mg), citrate and alkali. C-NC is characterized by Kossa-positive areas located in cells of the proximal tubule close to blood vessels and also, to a lesser extent, within glomeruli. After ATx there was vascular overproduction of endothelin (ET-1) but decreased production of nitrate; in renal cortical tissue there was an excess of calcium over Mg and phosphorus and oxalate over citrate. In plasma there was an increase in calcium and creatinine within the normal range. Calcification of tubular cells was eliminated by a preparation containing potassium, sodium and bases (from citrate degradation and bicarbonate) in addition to Mg. Less effective than the latter was Mg-potassium citrate and least effective, Mg citrate. The former treatment also normalized calcemia and urinary nitrate, but only incompletely suppressed ET-1 and had no significant effect on glomerular calcification or tissue and urinary oxalate. Urinary ET-1 excess appeared directly related to the cortical tissue calcium/Mg ratio, and urinary excretion of Mg, citrate and total protein appeared to be inversely related to the severity of C-NC. It was concluded that (1) the highly inbred rat is prone to precipitation of calcium phosphate in the renal cortex; (2) this type of C-NC occurs in close proximity to and within renal vascular tissue and is associated with an imbalance of vasoconstrictors and vasodilators of endothelial origin; (3) effective inhibition of C-NC can be achieved by an alkalinizing combination of Mg, potassium, sodium and citrate, underscoring its utility in the prophylaxis of pathological calcium phosphate deposition. The significance of these findings for the etiology and treatment of clinical disorders with renal and vascular calcification is uncertain and requires further investigation.

Clinical characteristics of patients with increased urinary excretion of adrenaline in mild to moderate heart failure.

We have previously demonstrated that adrenaline (AD) is released into the circulation during acute myocardial infarction and is associated with a more severe clinical course. The role of elevated AD levels in congestive heart failure is not known. The study aimed to determine whether increased daily AD excretion is associated with more severe clinical symptoms and a more complicated clinical course in patients with exacerbation of congestive heart failure (CHF). Urinary excretion of AD, noradrenaline, magnesium (Mg), and potassium (K), serum levels of aldosterone, K, and Mg, as well as the incidence of arrhythmias (24-h Holter) were assessed in 49 patients with CHF New York Heart Association (NYHA) class II-III. The patients were allocated to two groups, with normal (Group 1) and increased (Group 2) excretion of AD. Groups 1 and 2 did not differ in respect of age, etiology of CHF, or the medication used. Also, left ventricular ejection fraction was similar in the two groups. However, left ventricular end-diastolic dimension was greater in Group 2 (61+/-9 vs. 55+/-11 mm, p<0.05), as was the proportion of patients in NYHA class III (74 vs. 40%). Group 2 was also characterized by increased urinary excretion of Mg (60+/-24 vs. 43+/-16 mg/24 h, p < 0.007) and the presence of more complex and numerous ventricular arrhythmias (74 vs. 37% and 68 vs. 33% of patients, respectively). Urinary excretion of AD is increased only in a subgroup of patients with CHF. These patients are characterized by a more advanced NYHA class, increased end-diastolic left ventricular diameter, and increased urinary excretion of magnesium. It is likely that all these factors contribute to the presence of more complex and numerous ventricular arrhythmias in this subgroup of patients.

Effect of dietary magnesium level on nephrocalcinosis and growth in rats.

We studied the extent of kidney calcification by varying dietary levels of Mg, based on pathological examinations and calcium (Ca) and magnesium (Mg) balance tests. AIN-76 diets containing varying levels of Mg--0.3 (-M), 1.3 (1/20M), 2.4 (1/10M), 9.2 (1/5M), 19 (control), 38 (2M), 102 (5M), and 187 (10M) mmol/kg diet--were fed to 3-week-old male Fischer-344 rats for 14d. Although the magnitude of abnormality was highest in kidney of rats fed the -M diet, the damage was normalized as the dietary level of Mg increased, with increasing serum Mg concentration and urinary excretion of Mg. We found almost no deposition of Ca in rats fed the 10M diet. The mechanism by which the high dietary Mg induces these effects most likely involves a competition between Mg and Ca for reabsorption in proximal and/or distal tubules, since these diets increased the urinary excretion of Ca. However, these high Mg diets decreased food intake and body weight gain compared with the control diet, although these indices were not decreased in rats fed the 2M diet. The results suggest that a dietary magnesium level approximately twice the normal level effectively reduces kidney calcification while maintaining normal growth in rats.

Daily magnesium supplementation on serum and urinary magnesium changes in rats during prolonged restriction of motor activity.

The objective of this investigation was to determine whether a plentiful magnesium (Mg2+) supplementation might be used to normalize or prevent Mg deficiency. This is manifested by increased rather than decreased serum Mg2+ concentration as is observed during prolonged hospitalization, which is developed during prolonged hypokinesia (HK) (decreased motor activity). Eighty male Wistar rats with an initial body weight of 370-390 g were used to perform the studies: They were equally divided into four groups: 1. Unsupplemented control animals (UCA); 2. Supplemented control animals (SCA); 3. Unsupplemented hypokinetic animals (UHA); and 4. Supplemented hypokinetic animals (SHA). For the simulation of the hypokinetic effect, the hypokinetic animals were kept in small individual cages made of wood which restricted their movements in all directions without hindering food and water intake. The control and hypokinetic supplemental animals receive 0.9 mg/mL Mg sulfate daily with their drinking water. Prior to and during the experimental period, urinary excretions of Mg, calcium, and phosphate along with their concentrations in serum, water intake, and urine excretion, and body weight were determined in the control and hypokinetic animals. In the supplemental and unsupplemental hypokinetic rats, urinary excretions and serum concentrations of electrolytes increased significantly, whereas serum concentration and urinary excretion thereof remained unchanged in the supplemented and unsupplemented control animals. It was concluded that a daily intake of large amounts of Mg supplementation cannot be used to prevent or normalize Mg deficiency in rats during prolonged exposure to HK.