Mechanisms of proximal tubule sodium transport regulation that link extracellular fluid volume and blood pressure

McDonough, Alicia A.

doi:10.1152/ajpregu.00002.2010

Cited by 163 publications

(179 citation statements)

References 62 publications

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“…Consistent with this finding, a clinical study in infants found an increase in serum potassium concentrations in infants who experienced birth asphyxia as compared with control infants, with the serum potassium values directly proportional to the severity of asphyxia (25). The increased urinary sodium reported here in asphyxiated spiny mice pups is also observed in human neonates following birth asphyxia (1) and is likely to be secondary to the limitations in sodium reabsorption capacity with tubular damage (26).…”

Section: Birth Asphyxia Leads To Kidney Damage and Delayed Maturationsupporting

confidence: 83%

Creatine pretreatment prevents birth asphyxia–induced injury of the newborn spiny mouse kidney

et al. 2012

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Background: acute kidney injury (aKI) is a major complication for infants following an asphyxic insult at birth. We aimed to determine if kidney structure and function were affected in an animal model of birth asphyxia and if maternal dietary creatine supplementation could provide an energy reserve to the fetal kidney, maintaining cellular respiration during asphyxia and preventing aKI. Methods: Pregnant spiny mice were maintained on normal chow or chow supplemented with creatine from day 20 gestation. On day 38 (term ~39 d), pups were delivered by cesarean section (c-section) or subjected to intrauterine asphyxia. Twenty-four hours after insult, kidneys were collected for histological or molecular analysis. Urine and plasma were also collected for biochemical analysis. results: aKI was evident at 24 h after birth asphyxia, with a higher incidence of shrunken glomeruli (P < 0.02), disturbance to tubular arrangement, tubular dilatation, a twofold increase (P < 0.02) in expression of Ngal (early marker of kidney injury), and decreased expression of the podocyte differentiation marker nephrin. Maternal creatine supplementation prevented the glomerular and tubular abnormalities observed in the kidney at 24 h and the increased expression of Ngal. conclusion: Maternal creatine supplementation may prove useful in ameliorating kidney injury associated with birth asphyxia.

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Section: Birth Asphyxia Leads To Kidney Damage and Delayed Maturationsupporting

confidence: 83%

Creatine pretreatment prevents birth asphyxia–induced injury of the newborn spiny mouse kidney

et al. 2012

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“…The rate of Na/H exchange might be modified by several parameters such as increased Na/H exchange rate of already inserted apical NHE, increased trafficking of NHE from the subapical region, increased NHE phosphorylation, or a combination of these possibilities. 36 Nevertheless, the approach we used to measure NHE activity only provides information about the rate of sodium/hydrogen exchange. We cannot rule out any of the above-mentioned possibilities.…”

Section: Hypertensionmentioning

confidence: 99%

Fructose Stimulates Na/H Exchange Activity and Sensitizes the Proximal Tubule to Angiotensin II

et al. 2014

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Abstract-The proximal nephron reabsorbs 60% to 70% of the fluid and sodium and most of the filtered bicarbonate via Na/H exchanger 3. Enhanced proximal nephron transport is implicated in hypertension. Our findings show that a fructose-enriched diet causes salt sensitivity. We hypothesized that fructose stimulates luminal Na/H exchange activity and sensitizes the proximal tubule to angiotensin II. Na/H exchange was measured in rat proximal tubules as the rate of intracellular pH (pH i ) recovery in fluorescent units/s. Replacing 5 mmol/L glucose with 5 mmol/L fructose increased the rate of pH i recovery (1.8±0.6 fluorescent units/s; P<0.02; n=8). Staurosporine, a protein kinase C inhibitor, blocked this effect. We studied whether this effect was because of the addition of fructose or removal of glucose. The basal rate of pH i recovery was first tested in the presence of a 0.6-mmol/L glucose and 1, 3, or 5 mmol/L fructose added in a second period. The rate of pH i recovery did not change with 1 mmol/L but it increased with 3 and 5 mmol/L of fructose. Adding 5 mmol/L glucose caused no change. Removal of luminal sodium blocked pH i recovery. With 5.5 mmol/L glucose, angiotensin II (1 pmol/L) did not affect the rate of pH i recovery (change, -1.1±0.5 fluorescent units/s; n=9) but it increased the rate of pH i recovery with 0.6 mmol/L glucose/5 mmol/L fructose (change, 4.0±2.2 fluorescent units/s; P<0.02; n=6). We conclude that fructose stimulates Na/H exchange activity and sensitizes the proximal tubule to angiotensin II. This mechanism is likely dependent on protein kinase C. These results may partially explain the mechanism by which a fructose diet induces

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“…The regulation of NCC by aldosterone seems logical, because at least the endportion of the DCT expresses the enzyme 11-beta-hydroxysteroid dehydrogenase II which rapidly inactivates glucocorticoids and hence provides mineralocorticoid-sensitivity to the epithelial cells [6]. The discovery that angiotensin II is also capable of activating NCC was more surprising, because its actions were believed to be confined to the proximal tubule [75]. By adrenalectomizing rats and selectively re-infusing aldosterone or angiotensin II, we were able to dissect the stimulatory effects of angiotensin II and aldosterone on NCC [118].…”

Section: Structure-function Relationshipmentioning

confidence: 99%

The sodium chloride cotransporter SLC12A3: new roles in sodium, potassium, and blood pressure regulation

Moes

Lubbe

Zietse

et al. 2013

Pflugers Arch - Eur J Physiol

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SLC12A3 encodes the thiazide-sensitive sodium chloride cotransporter (NCC), which is primarily expressed in the kidney, but also in intestine and bone. In the kidney, NCC is located in the apical plasma membrane of epithelial cells in the distal convoluted tubule. Although NCC reabsorbs only 5 to 10 % of filtered sodium, it is important for the fine-tuning of renal sodium excretion in response to various hormonal and non-hormonal stimuli. Several new roles for NCC in the regulation of sodium, potassium, and blood pressure have been unraveled recently. For example, the recent discoveries that NCC is activated by angiotensin II but inhibited by dietary potassium shed light on how the kidney handles sodium during hypovolemia (high angiotensin II) and hyperkalemia. The additive effect of angiotensin II and aldosterone maximizes sodium reabsorption during hypovolemia, whereas the inhibitory effect of potassium on NCC increases delivery of sodium to the potassium-secreting portion of the nephron. In addition, great steps have been made in unraveling the molecular machinery that controls NCC. This complex network consists of kinases and ubiquitinases, including WNKs, SGK1, SPAK, Nedd4-2, Cullin-3, and Kelch-like 3. The pathophysiological significance of this network is illustrated by the fact that modification of each individual protein in the network changes NCC activity and results in salt-dependent hypotension or hypertension. This review aims to summarize these new insights in an integrated manner while identifying unanswered questions.

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Mechanisms of proximal tubule sodium transport regulation that link extracellular fluid volume and blood pressure

Cited by 163 publications

References 62 publications

Creatine pretreatment prevents birth asphyxia–induced injury of the newborn spiny mouse kidney

Creatine pretreatment prevents birth asphyxia–induced injury of the newborn spiny mouse kidney

Fructose Stimulates Na/H Exchange Activity and Sensitizes the Proximal Tubule to Angiotensin II

The sodium chloride cotransporter SLC12A3: new roles in sodium, potassium, and blood pressure regulation

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