endothelin-1 and Magnesium-Deficiency

Functional biological markers or biomarkers are now available for many nutrients which are used as nutritional status markers. Most sources of these biomarkers are products or precursors of enzymatic processes that can be measured in serum and plasma. At this time measurements of total or ionized magnesium (Mg) in serum, plasma, cellular components, urine or Mg retention from a load test are performed, but they may not always reflect Mg nutritional status. Biomarkers for Mg are needed which would reflect changes in biochemical processes where Mg is involved. Biomarkers for Mg need to be identified and evaluated in both animals and humans, with a determination of possible factors that may affect the reaction and biomarker concentrations. Some possible biomarkers for Mg include the following: Na/K ATPase, thromboxane B2, C-reactive protein, and endothelin-1. Other possible biomarkers for Mg need to be identified.

Topics: Adenosine Triphosphatases; Biomarkers; C-Reactive Protein; Endothelin-1; Humans; Magnesium Deficiency; Nutritional Status; Thromboxane B2

Bronchopulmonary dysplasia (BPD) has been defined as a requirement for oxygen for more than 28 days because of chronic pulmonary changes, usually in a premature infant. About 50 per cent of very low birth weight (VLBW) infants who weigh 1 kg at birth and who survive 28 days will develop BPD. Since 80 per cent of fetal accretion of magnesium occurs during the third trimester, this population is also at risk for magnesium deficiency. This paper reviews evidence for a role of magnesium deficiency in the pathogenesis of BPD. Pathology in BPD that may be caused or aggravated by magnesium deficiency is noted. Agents or mediators that are increased in BPD and in BPD include: oxygen free radicals; the inflammatory cytokines interleukin (IL)-1 and IL-6, and tumour necrosis factor-alpha; vaso- and bronchoconstrictors thromboxane A2 (TXA2) and serotonin: vasoconstrictor, endothelin-1 (ET-1); and bronchoconstrictor, histamine. Magnesium deficiency increases the susceptibility of cells and tissues to peroxidation, worsens the inflammatory reaction, reduces the immune response, exaggerates catecholamine release in stress, and diminishes energy metabolism. Possibly because of the danger of magnesium toxicity and the difficulty in studying the preterm VLBW neonate, little is known about magnesium supplementation in this group. Such information must be gained through controlled studies on the effect of antepartum exposure to maternally administered magnesium sulphate on the VLBW infant, through carefully monitored postnatal administration of magnesium in an intensive care setting, or through evaluations of combined pre- and postnatal supplementation.

Topics: Animals; Bronchopulmonary Dysplasia; Chemokines; Endothelin-1; Free Radicals; Humans; Hydroxyeicosatetraenoic Acids; Immunoglobulins; Infant, Newborn; Infant, Very Low Birth Weight; Magnesium Deficiency; Nitric Oxide; Substance P; Thromboxane A2; Tumor Necrosis Factor-alpha

Topics: Child; Child, Preschool; Endothelin-1; Humans; Magnesium; Magnesium Deficiency; Protein-Energy Malnutrition; Risk Factors

The present study aimed to show whether long-term moderate magnesium (Mg)-deficient (150 mg/kg) and Mg-supplemented (3200 mg/kg) diets (versus control diet: 800 mg/kg), modified the occurrence of cardiovascular risk induced by aging in the rat.. Cardiovascular and arterial functions were determined by a systemic hemodynamic study and by ex vivo measurements of vasoconstriction and endothelium dependent-vasorelaxation. Arterial wall structure was determined using pressure myograph chamber and histomorphometric methods.. The main changes observed in old rats (96 weeks old) fed a control diet, in comparison to adult rats (16 weeks old) were increased pulse pressure, a loss of aortic endothelium-dependent relaxation, increased aortic wall thickness and a decrease of the aortic wall elastin/collagen ratio. Long-term moderate Mg deficiency progressively increased systolic blood pressure. Intra-arterial pulse pressure was higher in Mg-deficient old rats than in age-matched control rats. Histological examination showed that Mg deficiency increased the age-induced deleterious effects on composition and structure of aorta (media thickness, increased collagen content and reduction in the elastin/collagen ratio), which lead to large artery rigidity. Hypertension and increased pulse pressure may have contributed to the increase in the mortality rate observed in the hypertensive Mg-deficient group. Although the long-term Mg-supplemented diet lowered blood pressure and decreased the mortality rate, it had no significant effect on aortic wall thickening and stiffening.. It is suggested that a long-term and moderate Mg-deficient diet increases age-induced arterial thickness and stiffness in rats, and thus increases the cardiovascular risks incurred by aging.

Topics: Acetylcholine; Aging; Animals; Aorta; Blood Pressure; Cardiovascular Diseases; Dietary Supplements; Endothelin-1; Food, Formulated; Magnesium; Magnesium Deficiency; Male; Nitroprusside; Norepinephrine; Organ Culture Techniques; Rats; Rats, Sprague-Dawley; Risk Factors; Survival Rate; Time; Vasoconstrictor Agents; Vasodilator Agents; Vasomotor System

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-1-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-1-induced contractions in aortae from DOCA-salt hypertensive rats to a greater extent than in aortae from normotensive rats. 3. A high extracellular magnesium concentration (4.8 mM) attenuated endothelin-1-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-1-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-1-induced contractions in aortae from both normotensive and DOCA-salt hypertensive rats. In the absence of calcium, removal of magnesium totally inhibited endothelin-1-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-1-induced contractions in aortae from normotensive and DOCA-salt hypertensive rats. Conversely, the attenuating effect of magnesium removal on endothelin-1-induced contractions did not occur when endothelium was present. 6. In conclusion, endothelin-1-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-1-induced contraction in aortae from normotensive and hypertensive rats,

Topics: Animals; Aorta, Thoracic; Blood Pressure; Desoxycorticosterone; Endothelin-1; Endothelium, Vascular; Hypertension; In Vitro Techniques; Magnesium; Magnesium Deficiency; Male; Muscle Contraction; Muscle, Smooth, Vascular; Rats; Rats, Sprague-Dawley