Responses in extracellular and intracellular calcium and magnesium in aldosteronism

Runyan, Aliye L.; Sun, Yao; Bhattacharya, Syamal K.; Ahokas, Robert A.; Chhokar, Vikram S.; Gerling, Ivan; Weber, Karl T.

doi:10.1016/j.lab.2005.04.008

Cited by 15 publications

(15 citation statements)

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“…These findings are in contrast to those reported by Runyan et al 8 and Chhokar et al, 37 where aldosterone infusion induced hypermagnesuria. However, in those studies, 8,37 rats, not mice, were investigated, uninephrectomy was performed, and animals were infused for 4 to 6 wk. Hence the experimental protocol was different from our study.…”

Section: Discussioncontrasting

confidence: 94%

“…We also provide the first evidence that aldosterone modulates renal TRPM7 expression, which could be important in altered Mg 2ϩ homeostasis associated with hyperaldosteronism. 8,9,23 An unexpected finding in our study was the failure of aldosterone to induce hypertension. This may relate to the fact that the mice investigated here were not uninephrectomized as in many other studies.…”

Section: Discussionmentioning

confidence: 54%

“…8,9 In the aldosterone-infused mice, serum Na ϩ was increased and serum K ϩ was decreased confirming efficient absorption of the administered aldosterone. Reasons for these electrolytes changes are attributable to renal actions of aldosterone, which promote K ϩ excretion and Na ϩ reabsorption through activation of the Na ϩ /H ϩ exchanger, ENaC, and Na ϩ /K ϩ ATPase transporters.…”

Section: Discussionmentioning

confidence: 85%

“…6,7 The profibrotic and proinflammatory actions of aldosteronism are accompanied by disturbances in cation homeostasis including hypomagnesemia and decreased intracellular free magnesium concentration ([Mg 2ϩ ] i ). 8,9 Recent evidence suggests that aldosterone-induced cardiovascular inflammation is induced, in part, by decreased [Mg 2ϩ ] i with Ca 2ϩ loading leading to increased H 2 O 2 formation and cellular oxidative stress. 8 -10 Hyperaldosteronism-associated renal magnesium wasting and cardiovascular injury and fibrosis are ameliorated by spironolactone and eplerenone and by Mg 2ϩ administration.…”

mentioning

confidence: 99%

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Downregulation of Renal TRPM7 and Increased Inflammation and Fibrosis in Aldosterone-Infused Mice

et al. 2008

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Abstract-Hyperaldosteronism is associated with hypertension, cardiovascular fibrosis, and electrolyte disturbances, including hypomagnesemia. Mechanisms underlying aldosterone-mediated Mg 2ϩ changes are unclear, but the novel Mg 2ϩ transporters TRPM6 and TRPM7 may be important. We examined whether aldosterone influences renal TRPM6/7 and the TRPM7 downstream target annexin-1 and tested the hypothesis that Mg 2ϩ administration ameliorates aldosterone-induced cardiovascular and renal injury and prevents aldosterone-associated hypertension. C57B6 mice were studied (12 weeks, nϭ8 to 9/group); (1) control group (0.2% dietary Mg 2ϩ ), (2) Mg 2ϩ group (0.75% dietary Mg 2ϩ ), (3) aldosterone group (Aldo, 400 g/kg/min and 0.9% NaCl drinking water), and (4) AldoϩMg 2ϩ group. Blood pressure was unaltered by aldosterone and was similar in all groups throughout the experiment. Serum Na ϩ was increased and serum K ϩ and Mg 2ϩ decreased in the Aldo group. Aldo mice had hypomagnesuria and proteinuria, and renal, cardiac, and aortic fibrosis, which were normalized by Mg 2ϩ supplementation. Renal and cardiovascular expression of interleukin-6, VCAM1 and COX2 was increased in the Aldo group. Magnesium attenuated renal and cardiac interleukin-6 content and decreased renal VCAM1 and cardiac COX2 expression (PϽ0.05). Aldosterone decreased expression of renal TRPM7 and the downstream target annexin-1 (PϽ0.05) without effect on TRPM6. Whereas Mg 2ϩ increased mRNA expression of TRPM6 and TRPM7, it had no effect on TRPM7 and annexin-1 protein content. Our data demonstrate that aldosterone mediates blood pressure-independent renal and cardiovascular fibrosis and inflammation through Mg 2ϩ -sensitive pathways. We suggest that altered Mg 2ϩ metabolism in hyperaldosteronism may relate to TRPM7 downregulation and that Mg 2ϩ protects against cardiovascular and renal damaging actions of aldosterone. A ldosterone, classically thought to be produced by the zona glomerulosa of the adrenal cortex and implicated in the maintenance of sodium, potassium, and acid-base balance and blood pressure regulation, is now considered a hormone with pleiotropic actions, produced by multiple tissues, including the heart, vessels, kidney, and brain. 1,2 In addition to regulating renal electrolyte excretion, aldosterone contributes to vascular inflammation, oxidative stress, collagen deposition, and endothelial dysfunction. [3][4][5] As such, aldosterone has been implicated in the development of cardiovascular and renal remodeling, fibrosis, and injury. The importance of these processes in clinical medicine is being increasingly recognized by the cardiovascular and renal protective effects of the aldosterone antagonists, spironolactone and eplerenone. 6,7 The profibrotic and proinflammatory actions of aldosteronism are accompanied by disturbances in cation homeostasis including hypomagnesemia and decreased intracellular free magnesium concentration ([Mg 2ϩ ] i ). 8,9 Recent evidence suggests that aldosterone-induced cardiovascular inflammation is induced, in part...

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Section: Discussioncontrasting

confidence: 94%

Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 85%

mentioning

confidence: 99%

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Downregulation of Renal TRPM7 and Increased Inflammation and Fibrosis in Aldosterone-Infused Mice

et al. 2008

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“…113 Clinically, there are a number of well-defined conditions in which high blood pressure is associated with hypomagnesemia, including hyperaldosteronism, use of diuretics in the management of hypertension and congestive cardiac failure and treatment with calcineurin inhibitors as immunosuppressive drugs. 122, 123 Hyperaldosteronism is associated not only with increased systolic blood pressure but also with electrolyte imbalances, including hypomagnesemia, 124,125 possibly through modulation of TRPM6/TRPM7. 115, 116 In patients with congestive cardiac failure and hyperaldosteronism, spironolactone, a mineralocorticoid receptor blocker, improved arrythmias and prevented intraerythrocyte Mg 2+ depletion, 126 possibly through effects on cellular Mg 2+ transport systems as we showed in experimental models.…”

Section: Trpm7 Mg 2+ and Hypertensionmentioning

confidence: 99%

Transient Receptor Potential Melastatin 7 (TRPM7) Cation Channels, Magnesium and the Vascular System in Hypertension

Yogi

Callera

Antunes

et al. 2011

Circ J

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Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp ypertension is the most common chronic disease in developed and developing societies and a major risk factor for morbidity and mortality. 1, 2 The most common form of hypertension is 'essential hypertension' the causes of which remain unknown. Among the many factors implicated in the pathophysiology of hypertension are neurohumoral, renal, metabolic, race, genetic, environmental factors and alterations in cellular cations, such as sodium (Na + ), calcium (Ca 2+ ), potassium (K + ) and magnesium (Mg 2+ ) have been shown to be related to the increase in systolic blood pressure. 3-7Mg 2+ , an abundant intracellular divalent cation, functions as an allosteric modulator of several proteins, controls nucleotide and protein synthesis, regulates Na + , K + , and Ca 2+ channels and is critical for myriad enzymatic reactions, particularly those involving kinases. 8,9 Mg 2+ is stored primarily in bone and the intracellular compartments of muscle and soft tissues, with less than 1% of total body Mg 2+ circulating in the blood. 9,10 Mg 2+ homeostasis depends primarily on the balance between intestinal uptake and renal excretion. Mg 2+ deficiency results from reduced dietary intake, intestinal malabsorption or renal loss. Mammalian cells tightly control magnesium levels within a narrow range (0.70-1.1 mmol/L) by specific regulatory mechanisms operating at the level of intraorganelle compartmentalization, intracellular magnesium buffering and at regulating magnesium entry and efflux across the cell membrane.Epidemiological studies indicate that low Mg 2+ status is associated with many diseases including diabetes, metabolic syndrome, dyslipidemia and hypertension.

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Hyponatremia and other electrolyte/ion disorders

Piano

Morando

Angeli

2015

Cirrhosis: A Practical Guide to Management

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Responses in extracellular and intracellular calcium and magnesium in aldosteronism

Cited by 15 publications

References 49 publications

Downregulation of Renal TRPM7 and Increased Inflammation and Fibrosis in Aldosterone-Infused Mice

Downregulation of Renal TRPM7 and Increased Inflammation and Fibrosis in Aldosterone-Infused Mice

Transient Receptor Potential Melastatin 7 (TRPM7) Cation Channels, Magnesium and the Vascular System in Hypertension

Hyponatremia and other electrolyte/ion disorders

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