Aldosterone inhibits HCO-3 absorption via a nongenomic pathway in medullary thick ascending limb

2002 ◽  
Vol 283 (4) ◽  
pp. F699-F706 ◽  
Author(s):  
David W. Good ◽  
Thampi George ◽  
Bruns A. Watts
Keyword(s):  
Actinomycin D ◽  
Renal Tubule ◽  
Extracellular Fluid ◽  
Transepithelial Transport ◽  
Thick Ascending Limb ◽  
The Novel ◽  
Acid Base Balance ◽  
Acid Base ◽  
Medullary Thick Ascending Limb ◽  
Base Balance

Rapid actions of aldosterone that are independent of transcription and translation have been described in a variety of cells; however, whether nongenomic pathways mediate aldosterone-induced regulation of renal tubule transport has not been determined. We report here that aldosterone induces rapid (<3.5 min) inhibition of HCO[Formula: see text] absorption in the medullary thick ascending limb (MTAL) of the rat. This inhibition is observed over the physiological range of hormone concentrations (IC50 ≃ 0.6 nM) and is not affected by pretreatment with actinomycin D (12.5 μg/ml), cycloheximide (40 μg/ml), or spironolactone (10 μM). The glucocorticoids dexamethasone, cortisol, and corticosterone (1 or 500 nM) did not affect HCO[Formula: see text]absorption in the absence or presence of carbenoxolone. Thus the specificity of rapid aldosterone action is not dependent on 11β-hydroxysteroid dehydrogenase activity. The inhibition by aldosterone is additive to inhibition by angiotensin II and vasopressin, indicating that these factors regulate MTAL transport through distinct pathways. These results demonstrate that aldosterone inhibits HCO[Formula: see text] absorption in the MTAL via a pathway that is rapid, highly selective, independent of transcription and protein synthesis, and not mediated through the classic mineralocorticoid receptor. The results establish a role for nongenomic pathways in mediating aldosterone-induced regulation of transepithelial transport in the mammalian kidney. The novel action of aldosterone to inhibit luminal acidification in the MTAL may play a role in enabling the kidney to regulate acid-base balance independently of Na+ balance and extracellular fluid volume.

Long-term regulation of renal Na-dependent cotransporters and ENaC: response to altered acid-base intake

2000 ◽  
Vol 279 (3) ◽  
pp. F459-F467 ◽  
Author(s):  
Gheun-Ho Kim ◽  
Stephen W. Martin ◽  
Patricia Fernández-Llama ◽  
Shyama Masilamani ◽  
Randall K. Packer ◽  
...  
Keyword(s):  
Collecting Duct ◽  
Na Channel ◽  
Thick Ascending Limb ◽  
Acid Base Balance ◽  
Acid Base ◽  
Opposite Pattern ◽  
Α Subunit ◽  
Base Balance ◽  
Acid Loading

Increased systemic acid intake is associated with an increase in apical Na/H exchange in the renal proximal tubule mediated by the type 3 Na/H exchanger (NHE3). Because NHE3 mediates both proton secretion and Na absorption, increased NHE3 activity could inappropriately perturb Na balance unless there are compensatory changes in Na handling. In this study, we use semiquantitative immunoblotting of rat kidneys to investigate whether acid loading is associated with compensatory decreases in the abundance of renal tubule Na transporters other than NHE3. Long-term (i.e., 7-day) acid loading with NH4Cl produced large decreases in the abundances of the thiazide-sensitive Na-Cl cotransporter (TSC/NCC) of the distal convoluted tubule and both the β- and γ-subunits of the amiloride-sensitive epithelial Na channel (ENaC) of the collecting duct. In addition, the renal cortical abundance of the proximal type 2 Na-dependent phosphate transporter (NaPi-2) was markedly decreased. In contrast, abundances of the bumetanide-sensitive Na-K-2Cl cotransporter of the thick ascending limb and the α-subunit of ENaC were unchanged. A similar profile of changes was seen with short-term (16-h) acid loading. Long-term (7-day) base loading with NaHCO3resulted in the opposite pattern of response with marked increases in the abundances of the β- and γ-subunits of ENaC and NaPi-2. These adaptations may play critical roles in the maintenance in Na balance when changes in acid-base balance occur.

scholarly journals Extracellular Acid-Base Balance and Ion Transport Between Body Fluid Compartments

Physiology ◽  
2017 ◽  
Vol 32 (5) ◽  
pp. 367-379 ◽  
Author(s):  
Julian L. Seifter ◽  
Hsin-Yun Chang
Keyword(s):  
Ion Transport ◽  
Ph Regulation ◽  
Extracellular Fluid ◽  
Transport Processes ◽  
Electrolyte Balance ◽  
Ph Homeostasis ◽  
Acid Base Balance ◽  
Acid Base ◽  
Base Balance ◽  
Fluid Compartments

Clinical assessment of acid-base disorders depends on measurements made in the blood, part of the extracellular compartment. Yet much of the metabolic importance of these disorders concerns intracellular events. Intracellular and interstitial compartment acid-base balance is complex and heterogeneous. This review considers the determinants of the extracellular fluid pH related to the ion transport processes at the interface of cells and the interstitial fluid, and between epithelial cells lining the transcellular contents of the gastrointestinal and urinary tracts that open to the external environment. The generation of acid-base disorders and the associated disruption of electrolyte balance are considered in the context of these membrane transporters. This review suggests a process of internal and external balance for pH regulation, similar to that of potassium. The role of secretory gastrointestinal epithelia and renal epithelia with respect to normal pH homeostasis and clinical disorders are considered. Electroneutrality of electrolytes in the ECF is discussed in the context of reciprocal changes in Cl−or non Cl−anions and [Formula: see text].

Chronic metabolic acidosis upregulates rat kidney Na-HCO 3 − cotransporters NBCn1 and NBC3 but not NBC1

2002 ◽  
Vol 282 (2) ◽  
pp. F341-F351 ◽  
Author(s):  
Tae-Hwan Kwon ◽  
Christiaan Fulton ◽  
Weidong Wang ◽  
Ira Kurtz ◽  
Jørgen Frøkiær ◽  
...  
Keyword(s):  
Metabolic Acidosis ◽  
Rat Kidney ◽  
Free Access ◽  
Thick Ascending Limb ◽  
Acid Base Balance ◽  
Acid Base ◽  
Chronic Metabolic Acidosis ◽  
Daily Water Intake ◽  
Base Balance ◽  
Access To Water

Several members of the Na-HCO[Formula: see text] cotransporter (NBC) family have recently been identified functionally and partly characterized, including rkNBC1, NBCn1, and NBC3. Regulation of these NBCs may play a role in the maintenance of intracellular pH and in the regulation of renal acid-base balance. However, it is unknown whether the expressions of these NBCs are regulated in response to changes in acid-base status. We therefore tested whether chronic metabolic acidosis (CMA) affects the abundance of these NBCs in kidneys using two conventional protocols. In protocol 1, rats were treated with NH4Cl in their drinking water (12 ± 1 mmol · rat−1 · day−1) for 2 wk with free access to water ( n = 8). Semiquantitative immunoblotting demonstrated that whole kidney abundance of NBCn1 and NBC3 in rats with CMA was dramatically increased to 995 ± 87 and 224 ± 35%, respectively, of control levels ( P < 0.05), whereas whole kidney rkNBC1 was unchanged (88 ± 14%). In protocol 2, rats were given NH4Cl in their food (10 ± 1 mmol · rat−1 · day−1) for 7 days, with a fixed daily water intake ( n = 6). Consistent with protocol 1, whole kidney abundances of NBCn1 (262 ± 42%) and NBC3 (160 ± 31%) were significantly increased compared with controls ( n = 6), whereas whole kidney rkNBC1 was unchanged (84 ± 17%). In both protocols, immunocytochemistry confirmed upregulation of NBCn1 and NBC3 with no change in the segmental distribution along the nephron. Consistent with the increase in NBCn1, measurements of pH transients in medullary thick ascending limb (mTAL) cells in kidney slices revealed two- to threefold increases in DIDS- sensitive, Na+-dependent HCO[Formula: see text] uptake in rats with CMA. In conclusion, CMA is associated with a marked increase in the abundance of NBCn1 in the mTAL and NBC3 in intercalated cells, whereas the abundance of NBC1 in the proximal tubule was not altered. The increased abundance of NBCn1 may play a role in the reabsorption of NH[Formula: see text] in the mTAL and increased NBC3 in reabsorbing HCO[Formula: see text].

Interactions between cutaneous ion-exchange mechanisms and acid–base balance in amphibians

1989 ◽  
Vol 67 (12) ◽  
pp. 3070-3077 ◽  
Author(s):  
Daniel F. Stiffler
Keyword(s):  
Ion Exchange ◽  
Ion Transport ◽  
Extracellular Fluid ◽  
Ambystoma Tigrinum ◽  
Acid Base Balance ◽  
Acid Base ◽  
Homeostatic Process ◽  
Base Balance ◽  
Net Flux ◽  
Exercise Induced

It has been suspected for over 50 years that amphibian ion exchange involves independent transport of Na+ and Cl− in an inward direction across the skin in exchange for acidic cations and basic anions, respectively. Although a role for such exchange mechanisms has obvious utility in acid–base balance, their participation in this homeostatic process has only recently been documented. We now know that in aquatic Ambystoma tigrinum, the presence of NaCl in the water bathing the skin is required for acid–base regulatory responses to hypercapnia and exercise-induced lactacidosis. Acidotic and alkalotic conditions in the animals' extracellular fluid cause changes in both Na+ and Cl− influx and net flux which are consistent with a role for ion transport in acid–base balance. These processes appear to be under the control of both catecholamines and interrenal steroids.

Peptide hormone effects on urinary acidification and acid-base balance: PTH, ADH, and glucagon

1989 ◽  
Vol 256 (6) ◽  
pp. F973-F985 ◽  
Author(s):  
M. Paillard ◽  
M. Bichara
Keyword(s):  
Peptide Hormones ◽  
Hormonal Control ◽  
Urinary Flow ◽  
Thick Ascending Limb ◽  
Acid Base Balance ◽  
Acid Base ◽  
Urinary Acidification ◽  
Corticosteroid Hormones ◽  
Base Balance ◽  
Collecting Tubules

That the adaptation of the kidney to the acid-base status may be controlled by peptide hormones is considered. In the proximal tubule parathyroid hormone (PTH) inhibits reabsorption of both bicarbonate and phosphate. The former effect is compensated for by an increase in bicarbonate absorption in Henle's loop, and the latter effect serves to augment phosphate concentration in the distal tubular fluid, which stimulates proton secretion in collecting ducts, the net effect of PTH administration being an enhancement of urinary acidification. In the thick ascending limb, both antidiuretic hormone (ADH) and glucagon inhibit bicarbonate absorption. In distal and cortical collecting tubules ADH stimulates net bicarbonate absorption and glucagon net bicarbonate secretion, which results in stimulation and inhibition of final urine acidification, respectively. Acute acid loading stimulates endogenous PTH secretion, which, by enhancing urinary acidification, constitutes a homeostatic response of the parathyroid glands. The major effects of ADH on urinary acidification serve at least to counterbalance disturbing consequences on urinary ammonia excretion of physiological variations in the urinary flow rate. The physiological significance of the effects of glucagon is unclear at present. Thus other peptide hormones may add to PTH and corticosteroid hormones to modulate urinary acidification, which leads to the concept of a pluri-hormonal control of acid-base balance.

Nongenomic regulation by aldosterone of the epithelial NHE3 Na+/H+ exchanger

2006 ◽  
Vol 290 (3) ◽  
pp. C757-C763 ◽  
Author(s):  
David W. Good ◽  
Thampi George ◽  
Bruns A. Watts
Keyword(s):  
Epithelial Transport ◽  
Extracellular Fluid ◽  
Thick Ascending Limb ◽  
Acid Base ◽  
Medullary Thick Ascending Limb ◽  
Contrast Exposure ◽  
Ph Range ◽  
Nongenomic Pathway ◽  
Direct Regulation ◽  
Exchange Activity

The relevance of nongenomic pathways to regulation of epithelial function by aldosterone is poorly understood. Recently, we demonstrated that aldosterone inhibits transepithelial HCO3− absorption in the renal medullary thick ascending limb (MTAL) through a nongenomic pathway. Here, we examined the transport mechanism(s) responsible for this regulation, focusing on Na+/H+ exchangers (NHE). In the MTAL, apical NHE3 mediates H+ secretion necessary for HCO3− absorption; basolateral NHE1 influences HCO3− absorption by regulating apical NHE3 activity. In microperfused rat MTALs, the addition of 1 nM aldosterone rapidly decreased HCO3− absorption by 30%. This inhibition was unaffected by three maneuvers that inhibit basolateral Na+/H+ exchange and was preserved in MTALs from NHE1 knockout mice, ruling out the involvement of NHE1. In contrast, exposure to aldosterone for 15 min caused a 30% decrease in apical Na+/H+ exchange activity over the intracellular pH range from 6.5 to 7.7, due to a decrease in Vmax. Inhibition of HCO3− absorption by aldosterone was not affected by 0.1 mM lumen Zn2+ or 1 mM lumen DIDS, arguing against the involvement of an apical H+ conductance or apical K+-HCO3− cotransport. These results demonstrate that aldosterone inhibits HCO3− absorption in the MTAL through inhibition of apical NHE3, and identify NHE3 as a target for nongenomic regulation by aldosterone. Aldosterone may influence a broad range of epithelial transport functions important for extracellular fluid volume and acid-base homeostasis through direct regulation of this exchanger.

Distribution of H+ and HCO3 minus between CSF and blood during metabolic acidosis in dogs

1975 ◽  
Vol 228 (4) ◽  
pp. 1134-1140 ◽  
Author(s):  
EG Pavlin ◽  
TF Hornbein
Keyword(s):  
Metabolic Acidosis ◽  
Extracellular Fluid ◽  
Acid Base Balance ◽  
Ion Distribution ◽  
Acid Base ◽  
Control Series ◽  
Base Balance ◽  
Active Ion Transport ◽  
Arterial Plasma ◽  
Lumbar Cerebrospinal Fluid

To determine whether the regulation of brain extracellular fluid acid-base balance is by active ion transport or passive distribution, changes in cisternal and lumbar cerebrospinal fluid (CSF) (H+) and (HCO3 minus) were assessed in five dogs with normal acid-base status and in six dogs during metabolic acidosis. Both groups were mechanically ventilated to maintain a constant PaCO2. The pH, PCO2, (HCO3 minus), and (lactate) in CSF and arterial plasma and the CSF/plasma DC potential difference were determined at intervals, and the electrochemical potential differnces (mu) for H+ and HCO3 minus were calculated. Following control measurements at pHa equal to 7.40, metabolic acidosis was induced by infusion of 0.6 N HCl. Measurements were made 0, 3, 4.5, and 6 h thereafter and at 0, 3, and 6 h in the control series. A steady state for ion distribution was reached by 4.5 h. In the control series at 6 h the values of mu for H+ and HCO3 minus were within minus 0.2 and +0.5 mV of initial values at the cistern and +0.1 and +0.9 mV at the lumbar site. During metabolic acidosis, the 6-h values at the cistern returned to 0.0 and +0.7 mV of control for muH+ and muHCO3 minus while lumbar values returned to +0.5 and minus 0.4 mV. The closeness of these 6-h values of mu to control is compatible with passive distribution of H+ and HCO3 minus between CSF and blood.

scholarly journals The effect of 60 km endurance exercise on serum electrolytes and acid–base balance in the Žemaitukai horses

2020 ◽  
Vol 89 (2) ◽  
pp. 125-131
Author(s):  
Indrė Poškienė ◽  
Vida Juozaitienė ◽  
Renata Gruodytė ◽  
Ramūnas Antanaitis
Keyword(s):  
Carbon Dioxide ◽  
Endurance Exercise ◽  
Base Excess ◽  
Haemoglobin Concentration ◽  
Extracellular Fluid ◽  
Total Carbon ◽  
Acid Base Balance ◽  
Acid Base ◽  
Blood Indices ◽  
Base Balance

The Lithuanian Žemaitukai horse breed is one of the oldest in Europe. Currently, there is a lack of information about the effect of endurance competition on blood indices and acid–base balance in the Žemaitukai horses. The aim of this study was to evaluate the effect of endurance exercise on the acid–base balance and electrolyte indicators of the Žemaitukai horses in an official endurance competition. In total, 48 horses of the Žemaitukai breed competed in endurance competitions over the same distance (60 km). Samples were taken before and immediately after the exercise. The following indicators were analysed: the hydrogen potential (pH), partial carbon dioxide pressure (pCO2), partial oxygen pressure (pO2), base excess in blood (BE), base excess in the extracellular fluid [BE (ecf)], cHCO3 (bicarbonate), cSO2 (oxygen saturation), tCO2 (blood total carbon dioxide), haematocrit (HCT), haemoglobin concentration (cHgb), sodium (Na), potassium (K), calcium (Ca), chlorides (Cl), and lactate (Lac). Increase in pH showed adaptation of the horse metabolism to exercise. Blood changes were caused by the development of dehydration and metabolic alkalosis. According to Lac results, all horses were fit and tolerated well physical activity. The exercise did not significantly affect the demand for minerals. Based on the results obtained, it can be stated that horses of the Žemaitukai breed are suitable for endurance competing.

Higher Dietary Acidity is Associated with Lower Bone Mineral Density in Postmenopausal Iranian Women, Independent of Dietary Calcium Intake

2014 ◽  
Vol 84 (3-4) ◽  
pp. 0206-0217 ◽  
Author(s):  
Seyedeh-Elaheh Shariati-Bafghi ◽  
Elaheh Nosrat-Mirshekarlou ◽  
Mohsen Karamati ◽  
Bahram Rashidkhani
Keyword(s):  
Calcium Intake ◽  
Dietary Calcium ◽  
Dietary Calcium Intake ◽  
Dietary Intakes ◽  
Iranian Women ◽  
Acid Base Balance ◽  
Mineral Density ◽  
Acid Base ◽  
Base Balance ◽  
Dietary Acid

Findings of studies on the link between dietary acid-base balance and bone mass are relatively mixed. We examined the association between dietary acid-base balance and bone mineral density (BMD) in a sample of Iranian women, hypothesizing that a higher dietary acidity would be inversely associated with BMD, even when dietary calcium intake is adequate. In this cross-sectional study, lumbar spine and femoral neck BMDs of 151 postmenopausal women aged 50 - 85 years were measured using dual-energy x-ray absorptiometry. Dietary intakes were assessed using a validated food frequency questionnaire. Renal net acid excretion (RNAE), an estimate of acid-base balance, was then calculated indirectly from the diet using the formulae of Remer (based on dietary intakes of protein, phosphorus, potassium, and magnesium; RNAERemer) and Frassetto (based on dietary intakes of protein and potassium; RNAEFrassetto), and was energy adjusted by the residual method. After adjusting for potential confounders, multivariable adjusted means of the lumbar spine BMD of women in the highest tertiles of RNAERemer and RNAEFrassetto were significantly lower than those in the lowest tertiles (for RNAERemer: mean difference -0.084 g/cm2; P=0.007 and for RNAEFrassetto: mean difference - 0.088 g/cm2; P=0.004). Similar results were observed in a subgroup analysis of subjects with dietary calcium intake of >800 mg/day. In conclusion, a higher RNAE (i. e. more dietary acidity), which is associated with greater intake of acid-generating foods and lower intake of alkali-generating foods, may be involved in deteriorating the bone health of postmenopausal Iranian women, even in the context of adequate dietary calcium intake.

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