Effects of metabolic acidosis and alkalosis on sodium and calcium transport in the dog kidney

Studies were performed to determine whether ammoniagenesis could adapt instantaneously to acidosis in the dog kidney. Following acute respiratory acidosis, renal glutamine extraction rose acutely in dogs with stable renal blood flow but did not change when the renal blood flow fell by more than 25%. Acute hypercapnia immediately increased renal ammonia production in both groups of dogs. The rate of both glutamine extraction and ammonia production in acutely hypercapnic dogs without hemodynamic changes was comparable to the rates observed in dogs with chronic metabolic acidosis. Furthermore, the renal metabolite profile observed in acute hypercapnia was similar to the pattern described in chronic metabolic acidosis, i.e., a marked fall in renal glutamate and alpha-ketoglutarate concentrations and a fivefold increase in malate and oxaloacetate concentrations. In the liver and muscle, acute hypercapnia induced no significant change in glutamine concentration but glutamate and alpha-ketoglutarate concentrations decreased. Our findings demonstrate that the dog kidney can adapt immediately to acidosis but that hemodynamic change may mask this adaptation.

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Chronic metabolic acidosis stimulated transcellular and solvent drag-induced calcium transport in the duodenum of female rats

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00108.2006 ◽

2006 ◽

Vol 291 (3) ◽

pp. G446-G455 ◽

Cited By ~ 42

Author(s):

Narattaphol Charoenphandhu ◽

Kukiat Tudpor ◽

Naritsara Pulsook ◽

Nateetip Krishnamra

Keyword(s):

Metabolic Acidosis ◽

Tight Junction ◽

Mrna Expression ◽

Calcium Transport ◽

Female Rats ◽

Calcium Balance ◽

Solvent Drag ◽

Chronic Metabolic Acidosis ◽

Active Calcium ◽

Relative Mrna Expression

Chronic metabolic acidosis results in a negative calcium balance as a result of bone resorption and renal calcium loss. However, reports on the changes in intestinal calcium transport have been controversial. The present investigation therefore aimed to study the effects of chronic metabolic acidosis induced by 1.5% NH4Cl administration on the three components of duodenal calcium transport, namely, solvent drag-induced, transcellular active, and passive paracellular components, in rats using an in vitro Ussing chamber technique. The relative mRNA expression of genes related to duodenal calcium transport was also determined. We found that 21-day chronic metabolic acidosis stimulated solvent drag-induced and transcellular active duodenal calcium transport but not passive paracellular calcium transport. Our results further demonstrated that an acute direct exposure to serosal acidic pH, in contrast, decreased solvent drag-induced calcium transport in a pH-dependent fashion but had no effect on transcellular active calcium transport. Neither the transepithelial resistance nor duodenal permeability to Na+, Cl−, and Ca2+ via the passive paracellular pathway were altered by chronic metabolic acidosis, suggesting that widening of the tight junction and changes in the charge-selective property of the tight junction did not occur. Thus the enhanced duodenal calcium transport observed in chronic metabolic acidosis could have resulted from a long-term adaptation, possibly at the molecular level. RT-PCR study revealed that chronic metabolic acidosis significantly increased the relative mRNA expression of duodenal genes associated with solvent drag-induced transport, i.e., the β1-subunit of Na+-K+-ATPase, zonula occludens-1, occludin, and claudin-3, and with transcellular active transport, i.e., transient receptor potential vanilloid family Ca2+ channels 5 and 6 and plasma membrane Ca2+-ATPase isoform 1b. Total plasma calcium and free ionized calcium and magnesium concentrations were also increased, whereas serum parathyroid hormone and 1α,25-dihydroxyvitamin D3 levels were not changed. The results indicated that 21-day chronic metabolic acidosis affected the calcium metabolism in rats partly through enhancing the mRNA expression of crucial duodenal genes involved in calcium absorption, thereby stimulating solvent drag-induced and transcellular active calcium transport in the duodenum.

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Effect of renal insufficiency on gastrointestinal transport of calcium

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1965.209.1.141 ◽

1965 ◽

Vol 209 (1) ◽

pp. 141-145 ◽

Cited By ~ 26

Author(s):

David M. Kessner ◽

Franklin H. Epstein

Keyword(s):

Vitamin D ◽

Metabolic Acidosis ◽

Renal Insufficiency ◽

Calcium Transport ◽

Intestinal Transport ◽

Chemical Gradient ◽

Subtotal Nephrectomy ◽

Solution Bathing ◽

High Doses ◽

Isolated Rat

Chronic experimental renal insufficiency induced by subtotal nephrectomy decreased the ability of the isolated rat duodenal gut sac to transport calcium against a chemical gradient. The defect in intestinal transport was not reproduced by metabolic acidosis, uremia of short duration, or addition of urea to the ambient solution bathing the gut sac. The transport of calcium by the intestine of uremic rats was increased by pretreatment with high doses of vitamin D and, at the dose level employed, there was no evidence of "resistance" to vitamin D. Dietary restriction depressed the gastrointestinal transport of calcium and may play a role in producing the defect in calcium transport of chronic uremia.

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Substrate utilization by the distal nephron in dogs with chronic metabolic acidosis: studies with ethacrynic acid

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y85-257 ◽

1985 ◽

Vol 63 (12) ◽

pp. 1565-1569 ◽

Cited By ~ 2

Author(s):

Mitchell L. Halperin ◽

Ching B. Chen

Keyword(s):

Metabolic Acidosis ◽

Ethacrynic Acid ◽

Proximal Convoluted Tubule ◽

Sodium Reabsorption ◽

Thick Ascending Limb ◽

Distal Nephron ◽

Chronic Metabolic Acidosis ◽

Fractional Excretion Of Sodium ◽

Renal Oxygen Consumption ◽

Dog Kidney

Glutamine and lactate oxidations provide the bulk of ATP required for sodium reabsorption in the dog kidney during chronic metabolic acidosis. Indirect evidence has suggested that glutamine is oxidized in the proximal convoluted tubule; if this is true, lactate should be the major fuel of the more distal nephron sites. The purpose of these experiments was to determine which substrates were metabolized by the acidotic dog kidney when a significant proportion of sodium chloride reabsorption was inhibited in the thick ascending limb of the loop of Henle. Ethacrynic acid, a loop diuretic, caused the fractional excretion of sodium to increase from 1 to 34%. The glomerular filtration rate declined somewhat, but there was no significant change in the renal blood flow rate. Renal oxygen consumption declined in conjunction with the natriuresis. However, when the data were examined at a constant filtered load of sodium (a constant rate of ATP turnover), there was no reduction in glutamine uptake or glutamine conversion to ATP in the presence of this natriuretic agent. The major change observed concerned lactate metabolism, in the presence of ethacrynic acid, there was no longer a significant rate of lactate extraction. These data are best explained by assuming that glutamine is the fuel of the proximal convoluted tubule of the acidotic dog kidney, whereas lactate oxidation occurs principally in the nephron sites where sodium reabsorption was inhibited by ethacrynic acid.

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Metabolic acidosis and parathyroidectomy increase Na+-H+ exchange in brush border vesicles

AJP Renal Physiology ◽

10.1152/ajprenal.1983.245.2.f217 ◽

1983 ◽

Vol 245 (2) ◽

pp. F217-F222 ◽

Cited By ~ 3

Author(s):

D. E. Cohn ◽

S. Klahr ◽

M. R. Hammerman

Keyword(s):

Metabolic Acidosis ◽

Brush Border ◽

Brush Border Membrane ◽

Membrane Vesicles ◽

Brush Border Membrane Vesicles ◽

Chronic Metabolic Acidosis ◽

Renal Brush Border Membrane ◽

Dog Kidney ◽

Renal Proximal Tubular ◽

Renal Brush Border

Na+-H+ exchange across the brush border membrane of the renal proximal tubular cell is a mechanism for Na+ reabsorption and H+ secretion. An electroneutral Na+-H+ exchange activity has been identified in isolated renal brush border membrane vesicles from rat and dog kidney, and increased Na+-H+ exchange has been measured in brush border membrane vesicles from remnant kidneys of dogs with chronic renal failure. To ascertain whether changes in H+ secretion by the kidney observed in chronic metabolic acidosis and in states of altered parathyroid function might result from altered Na+-H+ exchange across the renal cortical cellular brush border membrane, we measured Na+-H+ exchange in brush border membrane vesicles from kidneys of dogs with chronic metabolic acidosis and from kidneys of thyroparathyroidectomized dogs. Increased amiloride-sensitive Na+-H+ exchange was demonstrated in brush border membrane vesicles from kidneys of both groups of dogs, suggesting that adaptations in H+ excretion in chronic metabolic acidosis and hypoparathyroidism might be explained by increased activity of a renal brush border membrane Na+-H+ exchanger.

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