Adaptation of NHE-3 in the rat thick ascending limb: effects of high sodium intake and metabolic alkalosis
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The present studies examined the effects of chronic NaCl administration and metabolic alkalosis on NHE-3, an apical Na+/H+ exchanger of the rat medullary thick ascending limb of Henle (MTAL). NaCl administration had no effect on NHE-3 mRNA abundance as assessed by competitive RT-PCR, as well as on NHE-3 transport activity estimated from the Na+-dependent cell pH recovery of Na+-depleted acidified MTAL cells, in the presence of 50 microM Hoe-694, which specifically blocks NHE-1 and NHE-2. Two models of metabolic alkalosis were studied, one associated with high sodium intake, i.e., NaHCO3 administration, and one not associated with high sodium intake, i.e., chloride depletion alkalosis (CDA). In both cases, the treatment induced a significant metabolic alkalosis that was associated with a decrease in NHE-3 transport activity (-27% and -25%, respectively). Negative linear relationships were observed between NHE-3 activity and plasma pH or bicarbonate concentration. NHE-3 mRNA abundance and NHE-3 protein abundance, assessed by Western blot analysis, also decreased by 35 and 25%, respectively, during NaHCO3-induced alkalosis, and by 47 and 33%, respectively, during CDA. These studies demonstrate that high sodium intake has per se no effect on MTAL NHE-3. In contrast, chronic metabolic alkalosis, regardless of whether it is associated with high sodium intake or not, leads to an appropriate adaptation of NHE-3 activity, which involves a decrease in NHE-3 protein and mRNA abundance.Keywords:
Alkalosis
Bicarbonate
Sodium bicarbonate
Hypochloremia
Bicarbonate
Hydrochloric acid
Alkalosis
Sodium bicarbonate
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Bicarbonate
Alkalosis
Sodium bicarbonate
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The present studies examined the effects of chronic NaCl administration and metabolic alkalosis on NHE-3, an apical Na+/H+ exchanger of the rat medullary thick ascending limb of Henle (MTAL). NaCl administration had no effect on NHE-3 mRNA abundance as assessed by competitive RT-PCR, as well as on NHE-3 transport activity estimated from the Na+-dependent cell pH recovery of Na+-depleted acidified MTAL cells, in the presence of 50 microM Hoe-694, which specifically blocks NHE-1 and NHE-2. Two models of metabolic alkalosis were studied, one associated with high sodium intake, i.e., NaHCO3 administration, and one not associated with high sodium intake, i.e., chloride depletion alkalosis (CDA). In both cases, the treatment induced a significant metabolic alkalosis that was associated with a decrease in NHE-3 transport activity (-27% and -25%, respectively). Negative linear relationships were observed between NHE-3 activity and plasma pH or bicarbonate concentration. NHE-3 mRNA abundance and NHE-3 protein abundance, assessed by Western blot analysis, also decreased by 35 and 25%, respectively, during NaHCO3-induced alkalosis, and by 47 and 33%, respectively, during CDA. These studies demonstrate that high sodium intake has per se no effect on MTAL NHE-3. In contrast, chronic metabolic alkalosis, regardless of whether it is associated with high sodium intake or not, leads to an appropriate adaptation of NHE-3 activity, which involves a decrease in NHE-3 protein and mRNA abundance.
Alkalosis
Bicarbonate
Sodium bicarbonate
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Previous workers have shown that metabolic acidosis increases the apparent space through which administered bicarbonate is distributed. This finding has been ascribed to the accompanying acidemia and to the consequent availability of a large quantity of hydrogen ion that accumulates on nonbicarbonate tissue buffers during the development of acidosis. To test this hypothesis, bicarbonate space was measured in dogs with a broad range of steady-state plasma [HCO-3] in association with alkalemia as well as with acidemia. Appropriate combinations of pH and plasma [HCO-3] were achieved by pretreating the animals to produce graded degrees of each of the four cardinal, chronic acid-base disorders. Metabolic acidosis (n = 15) was produced by prolonged HCl-feeding; metabolic alkalosis (n = 17) by diuretics and a chloride-free diet; and respiratory acidosis (n = 9) and alkalosis (n = 8) by means of an environmental chamber. Animals with normal acid-base status (n = 4) were also studied. Sodium bicarbonate (5 mmol/kg) was infused over 10 min to the unanesthetized animals; observations were carried out over 90 min. The results obtained from animals with metabolic acid-base disturbances demonstrated an inverse relationship between bicarbonate space and initial plasma pH, confirming the previous findings of others. By contrast, the results obtained in animals with respiratory acid-base disturbances demonstrated a direct relationship between bicarbonate space and initial plasma pH. The pooled data revealed that bicarbonate space is, in fact, quite independent of the initial pH but is highly correlated with the initial level of extracellular [HCO-3]; dogs with low extracellular [HCO-3] (congruent to 10 meq/liter) whether acidemic or alkalemic, have a bicarbonate space that is 25% larger than normal and some 50% larger than in dogs with high extracellular [HCO-3] (congruent to 50 meq/liter). We conclude from these results that the increased bicarbonate space in metabolic acidosis (and respiratory alkalosis) does not reflect the availability of more hydrogen ions for release during bicarbonate administration, but merely evidences the wider range of titration (delta pH) of nonbicarbonate buffers that occurs during alkali loading whenever plasma [HCO-3] is low.
Alkalosis
Bicarbonate
Respiratory acidosis
Respiratory alkalosis
Acid–base homeostasis
Sodium bicarbonate
Acid–base reaction
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SUMMARY Clinicopathologic effects of rapid intravenous infusion of 3 L of 5% dextrose in water containing 150 g of sodium bicarbonate were evaluated in 8 clinically normal horses. A highly significant metabolic alkalosis was produced in all the horses. This response was maximal at the end of the 20-minute infusion but persisted for as long as 8 hours. Packed cell volume, total plasma proteins, plasma potassium, and plasma chloride concentration decreased significantly after infusion, while plasma sodium concentration increased significantly. The clinical and clinicopathologic responses of the horses were comparable to those in man and other animal species.
Sodium bicarbonate
Bicarbonate
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Severe metabolic alkalosis is often treated by infusion of arginine-HCl. Since we know that this substance leads to a supplemental increase of intracellular pH and fails to reduce intracellular bicarbonate concentration we use HCl for correction of this disturbance of acid-base equilibrium. 18 intensive-care patients with severe metabolic alkalosis were treated with an infusion of 0.2 m HCl. While base excess and sodium decreased significantly, chloride increased slightly. Arterial plasma pH, potassium, Hb, Hk, pCO2, pO2, and SO2 remained unchanged. Instructions for preparing different HCl solutions and advice on dosage are given.
Alkalosis
Bicarbonate
Hydrochloric acid
Sodium bicarbonate
Acid–base reaction
pCO2
Base excess
Base (topology)
Acid–base homeostasis
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Sodium bicarbonate abuse is unusual, and rarely reported. A patient was extensively investigated at several hospitals for a recurrent hypokalaemic metabolic alkalosis; it transpired that she had been abusing sodium bicarbonate for 8 years and had gained hospital admission at will by taking large amounts. She also showed features of the Munchausen syndrome.
Sodium bicarbonate
Bicarbonate
Alkalosis
Diabetic ketoacidosis
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Alkalosis
Bicarbonate
Acid–base reaction
Sodium bicarbonate
Acid–base homeostasis
Base (topology)
Intracellular pH
Intracellular Fluid
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Alkalosis
Sodium bicarbonate
Bicarbonate
Intracellular pH
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Bicarbonate
Fanconi syndrome
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