Biomedical subjects

J Ostensen

Publications and source records attributed to J Ostensen.

25 records · Page 2Linked to original sources

PubMed1989

Difference between hypertonic NaCl and NaHCO3 as osmotic diuretics in dog kidneys.

To compare the osmotic inhibitory effects of NaCl and NaHCO3 on proximal tubular fluid reabsorption, plasma osmolality was raised by 40 mosmol kg-1 H2O by infusing hypertonic NaCl and NaHCO3 in volume-expanded dogs receiving ethacrynic acid. In five dogs studied at constant plasma pH 7.5, both NaCl and NaHCO3 reduced water reabsorption by 29 +/- 2%. However, NaCl infusion reduced bicarbonate reabsorption by 31 +/- 2%, whereas bicarbonate reabsorption remained unchanged during NaHCO3 infusion. In six dogs, bicarbonate reabsorption was kept constant during NaCl and NaHCO3 infusion by adjustments of plasma pH. At similar glomerular filtration rates (42.4 +/- 2.9 ml min-1), water reabsorption was 28.7 +/- 1.7 ml min-1 in the control period, 29.4 +/- 2.5 ml min-1 during hypertonic NaCl infusion and 20.6 +/- 1.2 ml min-1 during hypertonic NaHCO3 infusion. Therefore, NaCl did not reduce proximal tubular water reabsorption by a direct osmotic effect. By calculating the regression coefficient for the relationship between measured chloride reabsorption and maximal convective chloride flux, the effective reflection coefficient for NaCl averaged 0.11 +/- 0.01. The combination of a low reflection coefficient and high permeability may explain why hypertonic NaCl is not an osmotic diuretic.

Animals↗

PubMed1989

Low oxygen cost of carbonic anhydrase-dependent sodium reabsorption in the dog kidney.

To examine the oxygen requirement of carbonic anhydrase-dependent sodium reabsorption in the proximal tubule, 18 anaesthetized dogs were studied under conditions of saturated distal NaCl reabsorption; the latter was accomplished by volume expansion (all groups) combined with infusion of loop diuretics (groups 1 and 3). Acetazolamide reduced HCO3- reabsorption by 602 +/- 32 mumol min-1 (55%, group 1) and by 777 +/- 103 mumol min-1 (66%, group 2). This was accompanied with a reduction in sodium reabsorption and oxygen consumption in a molar delta Na/delta O2 ratio of about 45 in both groups of dogs. The delta HCO3/delta O2 ratio averaged 16 +/- 1, which was not significantly different from the theoretical value of 18 expected for transcellular sodium transport by Na+, K+-ATPase. Mannitol (group 3) reduced NaCl reabsorption by 37 +/- 2% without affecting NaHCO3 reabsorption or oxygen consumption significantly. We conclude that carbonic anhydrase-dependent NaCl reabsorption in the proximal tubules is passive, and that NaHCO3 reabsorption is the only important active sodium transport which is sensitive to inhibition of carbonic anhydrase.

Acetazolamide↗

PubMed1989

Essentials of glomerulotubular balance.

In the proximal tubules, fractional reabsorption remains essentially unchanged during variations in glomerular filtration rate (GFR). Glomerulotubular balance (GTB), defined as the linear relationship between proximal tubular reabsorption and GFR, is quantitatively the most important regulator of tubular reabsorption, which may be stopped by inhibiting Na, K-ATPase activity completely. However, ouabain in doses inhibiting 80% of the Na, K-ATPases, exerts no effect on proximal reabsorption of water, NaCl and NaHCO3. At constant plasma pH, the same relationship between filtered and reabsorbed bicarbonate is obtained whether bicarbonate reabsorption is altered by varying GFR or plasma concentration of bicarbonate. In contrast, a selective rise in plasma NaCl concentration at constant plasma pH (hypernatremia) reduces NaHCO3 reabsorption and fails to stimulate NaCl reabsorption. Other characteristics of proximal tubular reabsorption are that nonreabsorbable solutes, such as mannitol, inhibit water and NaCl reabsorption with little or no change in NaHCO3 reabsorption and renal oxygen consumption. Mannitol reduces the slope of the GTB curve for NaCl but not for NaHCO3. Hypertonic NaHCO3 exerts an osmotic effect on proximal water and NaCl reabsorption comparable to that of mannitol, whereas hypertonic NaCl is without osmotic effect. By reducing plasma pH (hypercapnia at high plasma bicarbonate concentration), the slope of the GTB curves for NaCl and NaHCO3 can be greatly increased. By raising plasma pH either by hypocapnia or bicarbonate loading, proximal reabsorption of NaHCO3 and NaCl is greatly depressed and remains almost unaltered during variations of GFR (abolished GTB). Similarly, carbonic anhydrase inhibitors, such as acetazolamide, reduce the reabsorption of NaCl and NaHCO3 in the same proportion as a rise in plasma pH, and abolish GTB. Examinations of proximal tubular oxygen consumption indicate that the energy requirement for NaHCO3 reabsorption is as expected for transcellular transport by Na, K-ATPases, whereas proximal NaCl reabsorption requires no additional energy. These data indicate that transcellular energy-requiring NaHCO3 reabsorption provides the main osmotic force across the tight junction for paracellular reabsorption of proximal tubular fluid containing NaCl and other solutes of low reflection coefficient. The main factors influencing GTB are the filtered load of bicarbonate, plasma pH and nonreabsorbable solutes in the proximal tubular fluid.

Animals↗

PubMed1988

Effect of maleate on tubular protein reabsorption in dog kidneys.

To examine the effects on protein and electrolyte reabsorption of reducing the energy supply to the proximal tubules, an inhibitor of the citric acid cycle, maleate (600 mg.kg-1), was administered to anesthetized dogs during continuous ethacrynic acid infusion. One hour after infusion, maleate reduced renal oxygen consumption from 128 +/- 3 to 48 +/- 6 mumol.min-1. Comparisons at similar GFR showed that maleate reduced bicarbonate reabsorption by 65%, chloride reabsorption by 60% and phosphate reabsorption by 90%. Tubular reabsorption of lysozyme, determined by the 'trapped-label' method, was reduced by 97%. Total protein excretion in urine increased from 0.12 to 1.0 mg.min-1 and was not associated with a significant increase in brush border and lysosome marker enzymes. However, by superimposing a carbonic anhydrase inhibitor, acetazolamide (100 mg.kg-1), electrolyte reabsorption was slightly further reduced but protein excretion increased to 2.7 mg.min-1, coincidentally with a dramatic increase in enzyme excretion: approximately 20-fold in the brush border enzymes, alanine aminopeptidase and alkaline phosphatase, and 10-fold in the lysosomal enzymes, acid phosphatase and N-acetyl-beta-glucosaminidase. Our data indicate that maleate stops protein reabsorption without signs of acute tubular damage, whereas subsequent administration of acetazolamide results in tubular desquamation and albumin leakage.

Absorption↗

PubMed1987

How bicarbonate loading inhibits tubular reabsorption of NaCl in dog kidneys.

During continuous infusion of ethacrynic acid in dogs, changes in glomerular filtration rate (GFR) and PCO2 at constant plasma bicarbonate concentration (PHCO3) alter bicarbonate and chloride reabsorption in a ratio of 1:2. This ratio did not apply when PHCO3 was raised by bicarbonate loading in 11 anaesthetized volume-expanded dogs. A rise in PHCO3 from 30 to 54 mM at constant PCO2 and GFR reduced sodium reabsorption during ethacrynic acid infusion from 3586 +/- 725 to 2449 +/- 403 mumol min-1. Bicarbonate and chloride reabsorption were reduced in a ratio of 1:10. When plasma pH was restored from 7.8 to 7.5 by raising PCO2, the inhibitory effect on chloride reabsorption was halved. At constant plasma pH 7.5 a rise in PHCO3 from 20 to 30 mM reduced chloride reabsorption by 20%. A further 30% inhibition was caused by raising PHCO3 from 30 to 54 mM. Bicarbonate reabsorption was highest at PHCO3 54 mM, suggesting a large capacity for bicarbonate reabsorption if PHCO3 is raised at constant plasma pH 7.5. Water and NaCl reabsorption remaining during ethacrynic acid infusion is almost equally inhibited by alkalosis and by an osmotic effect of unreabsorbed NaHCO3.

Animals↗

PubMed1987

Mechanism of osmotic diuresis studied by infusion of NaHCO3 and mannitol in dogs.

To examine whether mannitol and NaHCO3 are equally potent inhibitors of proximal tubular fluid reabsorption, experiments were performed in 10 anaesthetized volume-expanded dogs during continuous infusion of ethacrynic acid. At plasma pH 7.5, a rise in plasma osmolality of 40 mosmol kg-1 reduced the remaining tubular fluid reabsorption in five dogs by 14 +/- 3% during NaHCO3 infusion and by 28 +/- 1% during mannitol infusion. Bicarbonate reabsorption increased by 25 +/- 5% during NaHCO3 infusion and decreased by 14 +/- 1% during mannitol infusion. At equal rates of bicarbonate reabsorption the inhibitory effects on tubular fluid and NaCl reabsorption were slightly less during mannitol than during NaHCO3 infusion. In five other dogs studied at constant plasma concentration of sodium, changes in bicarbonate reabsorption were avoided by raising plasma pH to 7.7 during NaHCO3 infusion and by reducing plasma pH to 7.4 during mannitol infusion. Tubular fluid reabsorption was reduced 32 +/- 4% by NaHCO3 and 34 +/- 4% by mannitol infusion, indicating equal inhibitory effects. The mechanism may be that the osmotic force for paracellular reabsorption of water and NaCl across the tight junction is equally reduced by equiosmolal increments in the NaHCO3 and mannitol concentration of the proximal tubular fluid.

Animals↗

PubMed1986

Hypernatremia inhibits NaHCO3 reabsorption and associated NaCl reabsorption in dogs.

To examine the effect of selective rise of plasma NaCl concentration (hypernatremia) on NaHCO3 reabsorption and associated NaCl reabsorption remaining during continuous ethacrynic acid infusion, hypertonic NaCl solution was infused in three groups of anesthetized volume-expanded dogs. In six dogs examined at constant hematocrit and plasma pH, bicarbonate and water reabsorptions were inversely related to PNa and reduced by 37% and 39% respectively by raising PNa from 140 to 200 mM. Chloride reabsorption remained essentially constant until PNa exceeded 170 to 180 mM. At PNa 200 mM, sodium reabsorption was reduced by 22 +/- 6%. In six other dogs, mechanical variations of GFR showed that the inhibitory effects of hypernatremia (PNa 199 +/- 3 mM) were less pronounced at low GFR. After subsequent administration of acetazolamide (30 mg/kg body wt), only 20% of control bicarbonate reabsorption remained and glomerulo-tubular balance was completely abolished. Both hypernatremia and acetazolamide inhibited NaHCO3 and NaCl reabsorption in a molar ratio of about 1:2, as in normonatremic dogs. Finally, experiments in six dogs showed that the inhibitory effects of hypernatremia (PNa 213 +/- 4 mM) were not altered by varying PCO2 and plasma pH. We conclude that hypernatremia inhibits paracellular water and NaCl reabsorption in the proximal tubules by reducing the osmotic force caused by transcellular NaHCO3 reabsorption. A rise in PNa does not stimulate transcellular NaCl reabsorption during distal inhibition by ethacrynic acid.

Acetazolamide↗