Alteration of Plasma Cation Levels in Rats Kept in Constant Light

A variety of reports indicate that some kind of interaction may exist between the pineal gland and cations. Of particular interest are the reports that indicate comparatively high levels of copper, manganese, and zinc in the pineal gland and that the pineal gland exhibits a circadian rhythm in calcium, magnesium, potassium, and sodium. There are, unfortunately, no reports suggesting a functional role for these findings. This study investigated circadian rhythms in circulating plasma cations in rats under 12/12 h light-dark cycle and in rats whose pineal function had been suppressed by exposure to constant light for 1 and 7 days. Neither of the treatments affected circulating potassium levels but had some significant effects on sodium concentration at a number of time points without affecting the total amount of sodium circulating in a 24 h period. Calcium, magnesium, and zinc plasma concentrations were little affected by 1 day of constant light, while 7 days of constant light caused a dramatic and highly significant increase in the circulating levels of the three cations. The plasma levels of copper, on the other hand, while also being unaffected by 1 day were significantly depressed by 7 days of constant light. It is apparent, therefore, that the pineal gland may be involved in regulation of circulating levels of the cations measured. The functional significance of these observations is not clear at this stage but warrants further investigation.     

长期补钾补钙对盐敏感儿童血压及其尿钠代谢的影响

为观察长期适量补充钾盐及钙盐对盐敏感儿童血压及其尿钠代谢的影响。对为期２年的补钾补钙随机双盲安慰剂对照试验的２６１名儿童进行了盐敏感性测定。结果显示：盐敏感性儿童，补钾补钙组２年期血压增长值较安慰剂组低４．３／４．８ｍｍＨｇ（Ｐ＜０．０５），前者血压增长幅度较后者低３．６／７．０个百分点（Ｐ＜０．０５）；而盐不敏感儿童，补充组与安慰剂组间血压变化无显著性差异。盐敏感性儿童经补钾补钙后，夜８小时尿钠排泄量明显增加（Ｐ＜０．０１），且后者与其血压增长幅度呈负相关（ｒ＝－０．３９，Ｐ＜０．０１）。提示，适量增加钾和钙的摄入，通过与钠离子的相互复合作用，促进尿钠排泄，可降低盐敏感儿童血压的增长幅度。     

心脏病患者红细胞钙泵、钠泵活性及离子转运与心功能的关系

目的探讨心脏病患者红细胞内Ｃａ２＋、Ｋ＋、Ｍｇ２＋及红细胞膜上钙泵、钠泵活性与病因、心功能级别、收缩和舒张功能的关系。方法测定１０１例不同病因心脏病患者及３８例健康人红细胞内Ｃａ２＋、Ｋ＋、Ｍｇ２＋及红细胞膜上Ｃａ２＋Ｍｇ２＋ＡＴＰ酶、Ｎａ＋Ｋ＋ＡＴＰ酶活性，并用超声心动图测定左室射血分数（ＬＶＥＦ值）及左房充盈分数（Ａｉ／Ｔ）、左室前１／３充盈分数（１／３Ｔｉ／Ｔ）分别表示收缩和舒张功能。结果心功能Ⅰ、Ⅱ级时，钙泵活性下降，红细胞内Ｃａ２＋显著升高，Ｋ＋、Ｍｇ２＋明显降低（Ｐ均＜０．０５）；心功能Ⅲ、Ⅳ级时，上述指标变化更明显（Ｐ均＜０．０１），且钠泵活性也显著下降（Ｐ＜０．０５）。上述指标在高血压病＋冠心病组、风湿性心脏病组、扩张型心肌病组间差异无显著性。结论钙泵、钠泵活性和离子转运异常与病因无明确关系，主要与心功能级别以及收缩、舒张功能有关     

Renal Excretion of Electrolytes in Patients on Long-term Diuretic Therapy for Arterial Hypertension and/or Congestive Heart Failure

ABSTRACT. Renal excretion, skeletal muscle content and plasma concentration of electrolytes were studied in 108 patients on long-term diuretic therapy for congestive heart failure and/or arterial hypertension. As reference populations served a group of 16 healthy volunteers and a group of 22 patients with liver cirrhosis, but not on diuretic therapy. Diuretic therapy was found to deprive the patients of their ability to conserve potassium and magnesium when there was a simultaneous cellular depletion of these ions. Magnesium excretion was found to be correlated to the skeletal muscle magnesium content. An inverted Na/K ratio in urine and a low magnesium excretion were fair indicators of cellular magnesium depletion.     

Evaluation of serum magnesium differences in hypertensive crises and control patients: A randomly matched case‐control study

Although the role of magnesium in blood pressure has been well studied among hypertensive patients, no study has explored the role of magnesium in hypertensive crises. The primary objective of this study is to evaluate the differences in serum magnesium levels between hypertensive crises patients and matched controls (age‐, sex‐, race‐, and diabetes‐matched) in a 1:1 random match. This study is a single‐center, retrospective, chart review, case‐control study of patients with hypertensive crises (case group) and patients without hypertensive crises (control group). Patients were included in the case group if they were 18 years of age or older with hypertensive crises and have a documented magnesium level. The control group patients were required to be 18 years of age or older, have no diagnosis of hypertensive crises, and have a documented magnesium level. The primary outcome of the study was to compare the mean serum magnesium in patients with hypertensive crises versus patients without hypertensive crises. Three hundred and fifty‐eight patients were included in the study: 179 patients in both the case group and control group. The primary outcome results showed that serum magnesium concentration was not significantly different between the case group (1.89 ± 0.29 mg/dl) and control group (1.90 ± 0.31 mg/dl) (p = .787). This study found no significant difference in serum magnesium levels in patients with hypertensive crises compared to a random matched control group. Larger observational or experimental studies may be useful to evaluate the effect of magnesium on blood pressure in hypertensive crises.     

Comparison of the mineral content of tap water and bottled waters

OBJECTIVES: Because of growing concern that constituents of drinking water may have adverse health effects, consumption of tap water in North America has decreased and consumption of bottled water has increased. Our objectives were to 1) determine whether North American tap water contains clinically important levels of calcium (Ca2+), magnesium (Mg2+), and sodium (Na+) and 2) determine whether differences in mineral content of tap water and commercially available bottled waters are clinically important. DESIGN: We obtained mineral analysis reports from municipal water authorities of 21 major North American cities. Mineral content of tap water was compared with published data regarding commercially available bottled waters and with dietary reference intakes (DRIs). MEASUREMENTS AND MAIN RESULTS: Mineral levels varied among tap water sources in North America and among bottled waters. European bottled waters generally contained higher mineral levels than North American tap water sources and North American bottled waters. For half of the tap water sources we examined, adults may fulfill between 8% and 16% of their Ca2+ DRI and between 6% and 31% of their Mg2+ DRI by drinking 2 liters per day. One liter of most moderate mineralization European bottled waters contained between 20% and 58% of the Ca2+ DRI and between 16% and 41% of the Mg2+ DRI in adults. High mineralization bottled waters often contained up to half of the maximum recommended daily intake of Na+. CONCLUSION: Drinking water sources available to North Americans may contain high levels of Ca2+, Mg2+, and Na+ and may provide clinically important portions of the recommended dietary intake of these minerals. Physicians should encourage patients to check the mineral content of their drinking water, whether tap or bottled, and choose water most appropriate for their needs.     

Effects of Non-Pharmacologic Therapy

Whereas there is no doubt that non-drug treatment of hypertension, and modifications in life-style to prevent an age-associated rise in arterial pressure are attractive concepts, opinions vary as to what advice should be offered to hypertensive patients and to populations at large. No modification in diet or life style has been demonstrated to reduce the complications of hypertension. Review of recent reports suggests that moderate exercise, weight reduction in the obese, and moderation of alcohol intake are usually effective in reducing arterial pressure and are unaccompanied by adverse effects. On the contrary, restriction of dietary sodium, or supplementation with potassium, calcium or magnesium have little or variable antihypertensive effects, are not readily accepted by a high percentage of the population, and could have adverse consequences. Other dietary modifications may reduce blood pressure, but additional research is needed to define the relevant component in the diet.     

Effect of replacement of extracellular sodium ions and of D-600 on the activation by adrenalin of adenylate cyclase in intact pigeon erythrocytes

The effect of replacement of extracellular Na⁺ by Li⁺, choline, K⁺ or sucrose on cyclic AMP formation in pigeon erythrocytes has been investigated. Replacement of extracellular Na⁺ by Li⁺, choline or sucrose but not by K⁺ inhibited the stimulation by adrenalin of cyclic AMP formation, but had no detectable effect on cyclic AMP content in the absence of adrenalin. This inhibition was observed in the presence or absence of extracellular Ca²⁺. The relative inhibition caused by Na⁺ removal decreased with increasing adrenalin concentration. It was concluded that extracellular Na⁺ or K⁺ ions were required for maximal activation of adenylate cyclase by low concentrations of adrenalin, and that this effect of monovalent cations may have been due to an effect on the affinity of the receptor for adrenalin.The verapamil derivative D-600 also inhibited the stimulation by adrenalin of cyclic AMP formation. This effect occurred in the absence of extracellular Ca²⁺ and hence seemed to be unrelated to the inhibition by D-600 of the slow Ca²⁺ channel in electrically excitable tissues.     

Interaction of serotonin and melatonin with sodium, potassium, calcium, lithium and aluminium

In the present study, we investigated the ability of serotonin and melatonin to bind metals that occur naturally in the brain. An electrochemical technique called adsorptive cathodic stripping voltammetry (AdCSV) was employed to study the metal-serotonin or metal melatonin interactions. The results show that both serotonin and melatonin form stable complexes with lithium and potassium, with serotonin favouring lithium over potassium, and melatonin favouring potassium over lithium. Coordination between either serotonin or melatonin and calcium was not favoured. The stability of the complexes formed between serotonin and the metals decreased with the metals as follows: Li+ > K+ > Al3+ > Na+ > Ca2-. The trend for melatonin-metal complexes was K+ > Li+ > Na+ > Al3+ > Ca2+ The binding and stable complex formation between both ligands, serotonin and melatonin with lithium, potassium and sodium is of biological importance. The binding of serotonin to lithium could provide an explanation for the therapeutic effects of lithium in depression treatment, whereas the binding of aluminium by melatonin could provide insight into the role of this element in the aetiology of Alzheimer's disease.     

Beta-adrenergic stimulation of pig myocytes with decreased cytosolic free magnesium prolongs the action potential and enhances triggered activity

INTRODUCTION: Heart failure results in chronic beta-adrenergic stimulation, repolarization lability, and arrhythmias associated with early afterdepolarizations (EADs) and delayed afterdepolarizations (DADs). Having described a significant reduction in intracellular free magnesium ([Mg2+]i) in experimental heart failure, we asked whether a reduction in [Mg2+]i would delay repolarization or facilitate EADs and/or DADs. METHODS AND RESULTS: Left ventricular myocytes were isolated from Yorkshire swine. Cytosolic free [Mg2+] was set at 0.12 mM (LoMg) or 1.2 mM (HiMg) through pipette dialysis. Action potentials (AP), Ca current (I(Ca)), and sodium/calcium exchange current (I(NCX)) were measured in the presence or absence of isoproterenol (2 microM) at 37 degrees C. Under basal conditions (0.1-Hz stimulation, 2 mM external [Ca2+]), reducing [Mg2+]i had no effect on AP duration and I(Ca) but did significantly enhance I(NCX). In contrast, during superfusion with isoproterenol, reduced [Mg2+]i caused a significant increase in AP duration at both 50% and 90% repolarization (APD50 and APD90) compared with HiMg (P < 0.05). LoMg cells manifested a high incidence of triggered activities, including spontaneous AP, EADs, and DADs (83.3% in LoMg, n = 12 vs 38.3% in HiMg, n = 13; P < 0.05). I(Ca) and I(NCX) were significantly increased in LoMg cells compared with HiMg cells (P < 0.05). CONCLUSION: Decreased cytosolic free magnesium prolongs AP duration and increases the incidence of triggered activity during beta-adrenergic stimulation. These effects may be due to increased I(Ca) and I(NCX) in the presence of reduced intracellular [Mg2+]. A magnesium-dependent increase in triggered activity coupled with delayed repolarization during beta-adrenergic stimulation could contribute to the arrhythmogenic substrate in heart failure.     

Evaluation of serum calcium differences in hypertensive crises and control patients: A randomly matched case‐control study

The role of calcium in blood pressure has been widely studied among hypertensive patients; however, no study has explored the role of calcium in hypertensive crises. The primary objective of this study is to evaluate the differences in serum calcium levels between hypertensive crises patients and a 1:1 random matched controls (age‐, sex‐, race‐, diabetes, and body mass index matched). This study is a single‐center, retrospective, chart review, case‐control study of patients with hypertensive crises (case group) and patients without hypertensive crises (control group). Patients were included in the case group if they were 18 years of age or older with hypertensive crises and have a documented calcium level. The control group patients were required to be 18 years of age or older, have a documented calcium level, and have no diagnosis of hypertensive crises. The primary outcome of the study was to compare the mean serum calcium in patients with hypertensive crises vs patients without hypertensive crises. Five hundred and sixty‐six patients were included in the study: 283 patients in both the case group and control group. The primary outcome results showed that serum calcium concentration was not significantly different between the case group (8.99 ± 0.78 mg/dL) and control group (8.96 ± 0.75 mg/dL) (P = .606). This study found no significant difference in serum calcium levels in patients with hypertensive crises compared to a random matched control group. Larger observational or experimental studies may be useful to evaluate the effect of calcium on blood pressure in hypertensive crises.     

Effects of melatonin on water metabolism and renal function in male Syrian hamsters (Mesocricetus auratus)

The pineal indoleamine, melatonin, has been shown to influence many physiological systems within the mammalian body. Few studies, however, have examined the influence of melatonin on renal function. This study investigated the effects of melatonin on water metabolism and renal function. Young adult male Syrian hamsters were maintained on a long photoperiod (LD 14:10) in metabolic cages. The animals received daily (1700) injections of either control vehicle or 25 micrograms of melatonin for 85 consecutive days. Melatonin administration resulted in significant increases in water consumption and urine production. Water budgets were also significantly influenced by melatonin, as were urinary osmolality, urinary sodium, and potassium concentrations, but urinary calcium concentrations were essentially unaltered. When excretion rates for sodium, potassium, and calcium were calculated, no differences were observed between the vehicle control and melatonin-treated groups. Injections of melatonin also significantly decreased plasma antidiuretic hormone (ADH). These results demonstrate that afternoon injections of melatonin can alter renal function, which may involve direct (i.e., on ADH secretion and/or thirst mechanisms) or indirect (i.e., behavioral) effects.     

Metabolic and clinical effects of oral magnesium supplementation in furosemide-treated patients with severe congestive heart failure

BACKGROUND: Magnesium depletion and hypomagnesemia are common among furosemide-treated patients with chronic congestive heart failure. HYPOTHESIS: This investigation evaluated clinical and metabolic effects of oral magnesium supplementation. METHODS: Ten patients with severe congestive heart failure maintained on high dose furosemide (> or = 80 mg/day) received a supplement of oral magnesium citrate 300 mg/daily for 30 days. Clinical parameters were followed, and peripheral blood mononuclear cell magnesium and zinc content, serum and urine magnesium, potassium, zinc, calcium, phosphorus, and creatinine were assessed. RESULTS: Peripheral blood mononuclear cell magnesium content and serum potassium rose significantly at the end of the study (2.09 +/- 1.89 to 3.99 +/- 2.26 micrograms/mg cell protein, p < 0.05, and 4.17 +/- 0.38 to 4.39 +/- 0.27 mEq/l, p < 0.05, respectively), while the other parameters remained unchanged. CONCLUSION: In some of these patients, oral magnesium supplementation is effective in achieving substantial increments in intracellular magnesium and serum potassium which, in turn, may have cardioprotective effects.     

The molecular and ionic specificity of antiarrhythmic drug actions

Virtually all clinical antiarrhythmic agents act by reducing ion channel conductance, with sodium (Na+), potassium (K+), and calcium (Ca++) channels the primary targets. Na+ channel blockers increase the risk of ischemic ventricular fibrillation and are relatively contraindicated in the presence of active coronary heart disease. Ca++ channel blockers suppress AV nodal conduction and are used to terminate reentrant supraventricular arrhythmias and control the ventricular response to atrial fibrillation. K+ channels constitute the most diverse group of cardiac ion channels. They are the primary targets of Class III antiarrhythmic drugs, the category of such agents presently undergoing the most active development. The rapid delayed rectifier, IKr, plays a key role in repolarization of all cardiac tissues and is the most common (and often only) target of action potential-prolonging drugs. Unfortunately, because of the ubiquity of IKr and the reverse use-dependent action potential prolongation that results from blocking it, IKr blockers are likely to cause torsades de pointes ventricular proarrhythmia. K+ channel blockers, such as amiodarone and azimilide, that affect the slow delayed rectifier IKs as well as IKr, appear to produce a more desirable rate-dependent profile of Class III action. Recently, much has been learned about the molecular basis of K+ channels based on their role in the congenital long QT syndrome. The availability of molecular clones that encode many of the channels in the human heart allows for the rapid screening of many potential new drugs, making possible the development of "designer" antiarrhythmic drugs with specific profiles of channel-blocking selectivity.     

Renal excretory responses to single and repeated administration of diuretics in healthy subjects: Clinical connotations

Administration of an initial oral dose of hydrochlorothiazide 25 mg to healthy subjects is followed by increased 24-hour urinary outputs of sodium, chloride, and potassium. On the fourth day of once-daily dosing with hydrochlorothiazide 25 mg, 24-hour natriuresis and chloriuresis are no longer augmented, but the elevation in 24-hour kaliuresis that follows the first dose remains unchanged. Twenty-four-hour urinary calcium output is consistently reduced during repeated once-daily administration of hydrochlorothiazide 25 mg.The first oral dose of the loop diuretic torasemide augments the average natriuresis and kaliuresis in the 6 hours immediately after dosing in healthy subjects, in a dose-dependent fashion, within the 2.5 to 10-mg range. These increased urinary outputs are followed by rebounds below postplacebo values between 6 and 24 hours after dosing. As a result of this biphasic response, torasemide 2.5 mg qualifies as a nondiuretic formulation (it does not elevate 24-hour natriuresis), whereas torasemide 5 and 10 mg qualify as diuretic formulations. After the seventh dose of torasemide 5 or 10 mg during a regimen of once-daily therapy, 24-hour urinary sodium and chloride outputs no longer differ from their postplacebo counterparts. Twenty-four-hour kaliuresis tends to increase in a dose-dependent fashion after the first dose of torasemide (torasemide 2.5 and 5 mg do not augment it significantly), but this tendency is no longer present after the seventh once-daily dose, when torasemide (2.5, 5, or 10 mg) does not elevate the mean 24-hour kaliuresis. Twenty-four-hour calciuresis tends to increase in a dose-dependent manner (torasemide 2.5 mg does not elevate it significantly) after the first dose of torasemide; this calciuretic effect does not change in intensity after 7 days of once-daily treatment.     

Zinc in the treatment of acute diarrhea: current status and assessment

The improved treatment of acute diarrhea in children during the past 35 years has reduced its morbidity and mortality substantially. However, better therapy still is required. This article reviews the role of oral rehydration solution in the treatment of acute diarrhea with particular attention to recent efforts to develop improved oral rehydration solution formulations. One promising approach is the administration of Zinc (Zn). Based on its beneficial effects in infections, including pneumonia, Zn has been shown to be effective in the treatment of acute diarrhea in several randomized controlled trials including subsequent meta-analyses. Thus, an emerging body of clinical data indicates that Zn can be useful for treating acute diarrhea. However, only limited information is known about the mechanism(s) by which Zn reduces diarrhea. Recent studies have indicated that Zn acts as a K channel blocker of adenosine 3',5'-cyclic monophosphate-mediated chlorine secretion, but may not affect either Ca2+- or guanosine 3',5'-cyclic monophosphate-mediated chlorine secretion. These data provide a strong rationale for further trials testing its efficacy in specific clinical settings and for more detailed physiologic studies examining how Zn exerts its antidiarrheal effect.