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O Mathisen

Publications and source records attributed to O Mathisen.

50 records · Page 3Linked to original sources
PubMed1979

Renal metabolic rate during changes in bicarbonate-dependent sodium reabsorption in the proximal tubules.

Previous studies indicate that water and at least 2 mol NaCl are reabsorbed in the proximal tubules for each mol NaHCO3 reabsorbed. To examine the effect on cortical energy metabolism of variations in this bicarbonate-dependent sodium reabsorption, the cortical metabolic rate was examined in anaesthetized dogs by the heat production technique during continuous infusion of saline and ethacrynic acid. Sodium reabsorption was altered either by intravenous infusion of a large dose of acetazolamide (500 mg/kg body wt) or by changing plasma Pco2 during metabolic alkalosis. Acetazolamide reduced bicarbonate reabsorption by 71 +/- 2%, sodium reabsorption by 54 +/- 2% and cortical heat production by 21 +/- 3%. A rise in Pco2 to 16.4 +/- 1.3 kPa during metabolic alkalosis increased sodium reabsorption by 25 +/- 3% and cortical heat production by 14 +/- 2%. A similar elevation of plasma Pco2 during metabolic acidosis had no effect on electrolyte reabsorption or the cortical metabolic rate. A reduction in Pco2 to 2.3 +/- 0.3 kPa reduced sodium reabsorption by 40 +/- 3% and cortical heat production by 19 +/- 2%. We conclude that a rise in proximal tubular reabsorption requires energy. However, the changes in energy requirement are small, accounting for previous failures to observe significant changes in cortical energy metabolism during less extensive changes of sodium reabsorption in the proximal tubules.

Acetazolamide↗
PubMed1979

Coupling of NaHCO3 and NaCl reabsorption in dog kidneys during changes in plasma PCO2.

To study the relationship between proximal tubular reabsorption of bicarbonate, sodium, and chloride, the effects of changes in plasma PCO2 were examined in anesthetized dogs. Distal tubular reabsorption was inhibited by ethacrynic acid; plasma bicarbonate concentration was kept constant at 33.4 +/- 0.3 mM; glomerular filtration rate (GFR) was varied over a wide range to examine glomerulotubular balance (constant fractional reabsorption). Hypercapnia (PCO2, 112.0 +/- 2.5 mmHg) increased bicarbonate reabsorption by about 30%, and hypocapnia (PCO2, 19.8 +/- 0.6 mmHg) decreased reabsorption of bicarbonate by more than 50% and altered reabsorption of sodium, chloride, and bicarbonate in the molar ratios 2.7:1.6:1, respectively. During hypercapnia the range of glomerulotubular balance was extended to a GFR 125% of control. During hypocapnia glomerulotubular balance was present only at GFR below 50% of control; reabsorption of bicarbonate sodium, and chloride was constant at GFR exceeding 50% of control. During metabolic acidosis hypercapnia had no significant effect on reabsorption of bicarbonate, sodium, and chloride. These observations support the hypothesis that bicarbonate reabsorption is the main driving force for osmotic reabsorption of water and NaCl in the proximal tubules.

Acidosis↗
PubMed1979

Re-examination of the dose-reponse relationship for the renal effect of acetozolamide.

To examine the effect of acetazolamide on tubular reabsorption of bicarbonate, plasma concentrations of bicarbonate, potassium and PCO2 were kept constant in volume expanded dogs. Intravenous infusion of acetazolamide reduced glomerular filtration rate (GFR) at all dose levels; after a dose of 30 mg/kg body wt GFR was reduced by about 30% and was not reduced further by increasing the infused dose of acetazolamide up to 500 mg/kg body wt. When control GFR was restored by raising systemic blood pressure, increments in filtered and excreted bicarbonate were not significantly different. At control GFR a linear relationship was obtained between bicarbonate reabsorption and log dose when acetazolamide was administered intravenously in doses ranging between 0.3 and 500 mg/kg body wt (r = 0.93). We conclude that a log dose-reponse relationship applies over a 25 times larger dose range than previously assumed.

Absorption↗
PubMed1978

Factors limiting renal proximal tubular reabsorption at high glomerular filtration rate.

To examine the factors limiting proximal reabsorption, distal reabsorption was inhibited by continuous infusion of ethacrynic acid in anaesthetized dogs. During combined infusion of ethacrynic acid and 0.9% saline, autoregulation of renal blood flow is impaired and glomerular filtration rate (GFR) can be varied by lowering or raising renal perfusion pressure. During lowering of GFR reabsorption of bicarbonate, chloride and sodium varied in proportion to reduction in GFR (glomerulotubular balance), but during elevation of GFR the increase in the filtered load of all three ions was excreted and a maximal rate of reabsorption was approached. Administration of acetazolamide reduced the reabsorption of bicarbonate, chloride and sodium in the ratio 1:2:3, whether GFR was at control, reduced (74% of control) or increased (124% of control). Renal blood flow was 80--90% greater at high than at low GFR. These observations indicate that bicarbonate concentration increases along the proximal tubules during elevation of GFR, until plasma bicarbonate concentration is approached at the distal end of the proximal tubules. From then on, bicarbonate reabsorption cannot be further raised by increasing GFR. Proximal tubular sodium reabsoption reaches a maximum at high GFR because NaCl reabsorption varies in proportion to bicarbonate reabsorption.

Acetazolamide↗
PubMed1978

Characteristics of transcellular NaCl reabsorption in the kidney.

To examine the characteristics of transcellular, energy-requiring NaCl reabsorption, increased delivery of tubular fluid of different bicarbonate and chloride composition to the outer medulla was achieved by infusion of acetazolamide (30 mg/kg body wt) or 0.9% NaCl in anaesthetized dogs. As an index of energy-requiring NaCltransport, cortical and outer medullary metabolism were determined by the heat production technique. Outer medullary metabolism was correlated to sodium excretion but not to chloride excretion. A rise in sodium excretion up to 20-25% of the filtered load during hydropenia was associated with a 70-80% increase in outer medullary metabolism. Further increments in sodium excretion induced by increasing systemic blood pressure and thereby increasing glomerular filtration rate or by infusing 2.9% NaCl did not significantly increase either reabsorption of sodium or cortical and outer medullary metabolism. By infusion of furosemide (2mg/kg body wt) sodium reabsorption and outer medullary heat production could be reduced below control values. These experiments show that sodium rather than chloride determine transcellular NaCl reabsorption. The maximal capacity of this reabsorption system is approached first at sodium excretion rates beyond the physiological range. Calculations based on clearance studies and heat production measurements, before and after furosemide infusion, indicate that transcellular NaCl reabsorption accounts for more than half of the NaCl reabsorption in the kidney.

Acetazolamide↗
PubMed1977

Oxygen requirement of renal Na-K-ATPase-dependent sodium reabsorption.

The oxygen requirement of the Na-K-ATPase-dependent sodium transport system was examined in anesthetized dogs infused with 15% mannitol-Ringer solutions at a rate of 35 ml/min. Because of renal vasodilatation and abolished autoregulation, filtered sodium (FNa) could be varied over a wide range by progressive aortic constriction. Sodium reabsorption (RNa) and renal oxygen consumption (RVO2) varied in proportion to FNa (r greater than 0.9). Ouabain, which inhibits Na-K-ATPases, reduced RVO2 by 45 +/- 6%. During subsequent aortic constriction, the ratio delta RNa/delta FNa averaged 0.45 (glomerulotubular balance) (r less than 0.9), whereas RVO2 was not significantly altered. Comparisons of deltaRNa/deltaFNa before and after ouabain administration, indicate that about half of an increase in sodium delivery to the distal nephron is reabsorbed by the Na-K-ATPase-dependent sodium transport system and that deltaRNa/deltaRVO2 (Na/O2 ratio) of this system averages 14.5 +/- 1.3. This Na/O2 ratio corresponds to 2.4 sodium ions transported per ATP dephosphorylated as found in other tissues.

Adenosine Triphosphatases↗
PubMed1976

Dopamine-induced dissociation between renal metabolic rate and sodium reabsorption.

The stimulatory effect of dopamine on renal energy metabolism and its relationship to changes in tubular sodium reabsorption and plasma concentration of free fatty acids (FFA) were examined in anesthetized dogs. Dopamine infused intravenously at 25 mug/kg body wt-min for 30-60 min increased renal oxygen consumption (Rvo2) by 28 +/- 3%; glomerular filtration rate rose from 37 +/- 3 to 40 +/- 2 ml/min without significant changes in sodium excretion. Plasma FFA increased about 6 times. Total-body metabolic rate increased to 152 +/- 7% and fell to 119 +/- 5% of control after normalizing plasma FFA by beta-pyridylcarbinol; Rvo2 remained unchanged. Cortical and outer medullary heat accumulation rated increased to 137 +/- 6 and 133 +/- 10% after 1 h and to 163 +/- 18 and 179 +/- 26% of control after 2 h of dopamine infusion without further changes in sodium reabsorption. Furosemide reduced cortical and outer medullary metabolic rates as much as in control experiments (14 +/- 8 and 69 +/- 7%, respectively). Hence, dopamine exerts a renal calorigenic effect which cannot be accounted for by increased sodium reabsorption or attributed to increased supply of FFA.

Animals↗
PubMed1976

Effect of acetazolamide on glomerular balance and renal metabolic rate.

Glomerulotubular balance, defined as proportionality between filtered and reabsorbed sodium during inhibition of sodium reabsorption in the thick ascending limb of Henle's loop (diluting segment), was examined in anaesthetized dogs by gradual reduction of renal arterial pressure. In control experiments, glomerulotubular balance applied over the whole rante of glomerular filtration rate (GFR) examined but was absent after acetazolamide administration (30 mg/kg/body wt) at GFR above 50% of control. Hence, the inhibitory effect of acetazolamide varied with GFR. At control GFR, acetazolamide reduced tubular sodium reabsorption by 32 +/- 2% chloride reabsorption by 34 +/- 3%, and bicarbonate reabsorption by 52 +/- 2%; no significant effect was observed at GFR below 50% of control. For each bicarbonate ion, three sodium ions and two chloride ions were inhibited. Measurements of renal oxygen consumption and heat accumulation rates showed that acetazolamide did not reduce renal metabolic rate significantly. It is proposed that energy-requiring hydrogen ion secretion occurs at unchanges rate during variations in GFR but that back leakage of hydrogen ions varies with bicarbonate concentration in tubular fluid. Net secretion of hydrogen ions is associated with bicarbonate transport into the intercellular space and is linked with sodium reabsorption. The concentration difference of bicarbonate salts over the tight junction (zonula occludens), which is much less permeable to bicarbonate than to sodium chloride, provides the osmotic force for reabsorption of water and sodium chloride from the tubular lumen into the intercellular space. Glomerulotubular balance is mediated by variations in filtered amounts of bicarbonate.

Acetazolamide↗