Aldosterone increases Na+-K+-ATPase activity in skeletal muscle of patients with Conn’s syndrome

Phakdeekitcharoen, Bunyong; Kittikanokrat, Wassana; Kijkunasathian, Chusak; Chatsudthipong, Varanuj

doi:10.1111/j.1365-2265.2010.03912.x

Cited by 18 publications

(27 citation statements)

References 36 publications

(74 reference statements)

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“…Overall, these findings suggest that extrarenal potassium homeostasis was responsible for the different levels of extracellular potassium between the groups. Some animal and human studies support the role of aldosterone in extrarenal potassium handling through gastrointestinal secretion or transcellular shifts (24)(25)(26)(27), but a trial in anephric patients failed to identify a significant effect of exogenous mineralocorticoid on extracellular potassium (28). Angiotensin II may have varying effects on distal renal potassium channels, but effects of ARB on these channels in other tissues and extrarenal potassium homeostasis are unknown (29).…”

Section: Discussionmentioning

confidence: 99%

Potassium Handling with Dual Renin-Angiotensin System Inhibition in Diabetic Nephropathy

Buren

Adams‐Huet

Nguyen³

et al. 2014

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are the cornerstones of pharmacologic therapy in diabetic nephropathy. Mineralocorticoid receptor blockers reduce proteinuria as single agents or add-on therapy to other renin-angiotensin-aldosterone system-inhibiting drugs in these patients. The long-term benefits and ultimate role of mineralocorticoid receptor blockers in diabetic nephropathy remain unknown. A clinical trial previously showed that the kalemic effect of spironolactone is higher than losartan when added to lisinopril in patients with diabetic nephropathy. The purpose of this study was to investigate if renal potassium handling was primarily responsible for that observation.Design, setting, participants, & measurements In a blinded, randomized, three-arm placebo-controlled clinical trial, 80 participants with diabetic nephropathy taking lisinopril (80 mg) were randomized to spironolactone (25 mg daily), losartan (100 mg daily), or placebo (trial dates from July of 2003 to December of 2006). Serum potassium, aldosterone, and 24-hour urine sodium, potassium, and creatinine were measured over 48 weeks. Differences were analyzed with repeated measures mixed models.Results Mean follow-up serum potassium was 5.0 mEq/L for spironolactone, 4.7 mEq/L for losartan (P=0.05 versus spironolactone), and 4.5 mEq/L for placebo (P,0.001 versus spironolactone; P=0.03 versus losartan). The difference in serum potassium was 0.23 mEq/L for losartan versus placebo (P=0.02), 0.43 mEq/L for spironolactone versus placebo (P,0.001), and 0.2 mEq/L for spironolactone versus losartan (P=0.05). Serum and urine potassium excretion and secretion rates were similar between groups throughout the study.Conclusion Spironolactone raised serum potassium more than losartan in patients with diabetic nephropathy receiving lisinopril, despite similar renal sodium and potassium excretion. This finding suggests that extrarenal potassium homeostasis contributes to hyperkalemia in these patients. A better understanding of extrarenal potassium homeostasis will provide an opportunity to use this drug more safely in patients with diabetic nephropathy as well as other patient populations.

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Section: Discussionmentioning

confidence: 99%

Potassium Handling with Dual Renin-Angiotensin System Inhibition in Diabetic Nephropathy

Buren

Adams‐Huet

Nguyen³

et al. 2014

Clinical Journal of the American Society of Nephrology

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“…This increase is positively correlated with serum aldosterone levels and reversed by adrenalectomy. 30 However, aldosterone treatment in animals decreases the abundance of Na + , K + -ATPase. 31 This apparently paradoxical effect is probably due to that profound hypokalemia in aldosterone-treated animals suppresses the expression of Na + , K + -ATPase.…”

Section: Na+ K+-atpase and Extracellular Potassium Homeostasismentioning

confidence: 99%

Extracellular Potassium Homeostasis: Insights from Hypokalemic Periodic Paralysis

Cheng

Kuo

Huang

2013

Seminars in Nephrology

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The extracellular potassium makes up only about 2% of the total body potassium store. The majority of the body potassium is distributed in the intracellular space, and of which about 80% is in skeletal muscle. Movement of potassium in and out of skeletal muscle thus plays a pivotal role in extracellular potassium homeostasis. The exchange of potassium between the extracellular space and skeletal muscle is mediated by specific membrane transporters. These include potassium uptake by Na+, K+-ATPase and release by inward rectifier K+ channels. These processes are regulated by circulating hormones, peptides, ions, and by physical activity of muscle as well as dietary potassium intake. Pharmaceutical agents, poisons and disease conditions also affect the exchange and alter extracellular potassium concentration. Here, we review extracellular potassium homeostasis focusing on factors and conditions that influence the balance of potassium movement in skeletal muscle. Recent findings that mutations of a skeletal muscle-specific inward rectifier K+ channel cause hypokalemic periodic paralysis provide interesting insights into the role of skeletal muscle in extracellular potassium homeostasis. These recent findings will be reviewed.

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“…It is known, for example, that the relative expression levels of NKCC1 and NKCC2 determine whether neuronal responses to gamma amino butyric acid (GABA), an important neurotransmitter, are excitatory (depolarizing) or inhibitory (hyper-polarizing) in the CNS (7). The relative protein expression levels and corresponding neurophysiological responses that they determine change during neuronal development, including olfactory bulb neuronal migration (25,32), and during peripheral sensory nerve regeneration follow-ing sectioning of the mouse sciatic nerve in vivo (40). Also, since GABA is a prevalent neurotransmitter that modifies neuronal excitability, altered NKCC1 regulation has been implicated in cases of epilepsy (12).…”

mentioning

confidence: 99%

“…ALD can exert its action by binding to mineralocorticoid receptors (type I) to form a complex that interacts with nuclear DNA to exert gene transcription and protein synthesis (40,56). The present study tested the hypothesis that ALD can directly and precisely increase NKCC1 expression.…”

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confidence: 99%

Direct control of Na⁺-K⁺-2Cl⁻-cotransport protein (NKCC1) expression with aldosterone

Ding

Frisina

Liu

et al. 2014

American Journal of Physiology-Cell Physiology

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Sodium/potassium/chloride cotransporter (NKCC1) proteins play important roles in Na+ and K+ concentrations in key physiological systems, including cardiac, vascular, renal, nervous, and sensory systems. NKCC1 levels and functionality are altered in certain disease states, and tend to decline with age. A sensitive, effective way of regulating NKCC1 protein expression has significant biotherapeutic possibilities. The purpose of the present investigation was to determine if the naturally occurring hormone aldosterone (ALD) could regulate NKCC1 protein expression. Application of ALD to a human cell line (HT-29) revealed that ALD can regulate NKCC1 protein expression, quite sensitively and rapidly, independent of mRNA expression changes. Utilization of a specific inhibitor of mineralocorticoid receptors, eplerenone, implicated these receptors as part of the ALD mechanism of action. Further experiments with cycloheximide (protein synthesis inhibitor) and MG132 (proteasome inhibitor) revealed that ALD can upregulate NKCC1 by increasing protein stability, i.e., reducing ubiquitination of NKCC1. Having a procedure for controlling NKCC1 protein expression opens the doors for therapeutic interventions for diseases involving the mis-regulation or depletion of NKCC1 proteins, for example during aging.

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Aldosterone increases Na+-K+-ATPase activity in skeletal muscle of patients with Conn’s syndrome

Cited by 18 publications

References 36 publications

Potassium Handling with Dual Renin-Angiotensin System Inhibition in Diabetic Nephropathy

Potassium Handling with Dual Renin-Angiotensin System Inhibition in Diabetic Nephropathy

Extracellular Potassium Homeostasis: Insights from Hypokalemic Periodic Paralysis

Direct control of Na⁺-K⁺-2Cl⁻-cotransport protein (NKCC1) expression with aldosterone

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Aldosterone increases Na+-K+-ATPase activity in skeletal muscle of patients with Conn’s syndrome

Cited by 18 publications

References 36 publications

Potassium Handling with Dual Renin-Angiotensin System Inhibition in Diabetic Nephropathy

Potassium Handling with Dual Renin-Angiotensin System Inhibition in Diabetic Nephropathy

Extracellular Potassium Homeostasis: Insights from Hypokalemic Periodic Paralysis

Direct control of Na+-K+-2Cl−-cotransport protein (NKCC1) expression with aldosterone

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Direct control of Na⁺-K⁺-2Cl⁻-cotransport protein (NKCC1) expression with aldosterone