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G Lemieux

Publications and source records attributed to G Lemieux.

At least 37 records · Page 2Linked to original sources
PubMed1986

Regulation of glutamine metabolism in dog kidney in vivo.

In summary, we propose: that renal ammoniagenesis is regulated both by factors dependent and independent of the acid-base status, the net effect of the ammoniagenic process on the proton balance being directly related to the rate of urinary ammonium excretion; that the renal metabolism of glutamine should not be examined independently of the metabolism of other substrate physiologically taken up by the kidney; that different pathways for glutamine metabolism will change during acid-base disorders of organic or nonorganic origin; that, among the main glutamine utilizing pathways, only the GLDH pathway is influenced directly by the acid-base status; the ammoniagenic transamination pathways is regulated by substrate availability in the kidney; that the lowest ammoniagenic flux in the kidney coincides with the rate of alanine production since alanine appears to derive directly from glutamine. When this pathway is stimulated without concomitant acidosis, most of the ammonia produced is not excreted in urine but released in the renal venous blood: thus, no significant effect on the acid-base balance is produced; that glutamine is metabolized by proximal kidney tubules of acidotic dogs probably through net oxidation; that the quantitative analysis of the metabolic consequence of this process indicates that the rate of ATP turnover at this site may effectively place an upper limit to the rate of glutamine oxidation, and ammonia production by the kidney, and that this limit is nearly reached in chronically acidotic animals.

Acid-Base Equilibrium↗
PubMed1986

Renal metabolism during four types of lactic acidosis in the dog including anoxia.

The present study was undertaken to evaluate the metabolic response of the kidney to lactic acidosis. Four types of lactic acidosis were induced in the dog: infusion of lactic acid, infusion of lactic acid with phenformin, administration of phenformin alone, and hypoxia by breathing 95% nitrogen. In all groups of animals, the same degree of acidosis was observed with plasma bicarbonate ranging from 12.8 to 14.9 mM. Plasma lactate concentration ranged from 3.0 to 8.1 mumol/mL. Renal ammoniagenesis failed to be influenced by lactic acidosis. As a matter of fact, it fell during anoxia. The extraction of glutamine by the kidney rose except during anoxia where it fell. The renal production of alanine rose during the infusion of lactic acid with and without phenformin. This coincided with the extraction of glutamine. The renal extraction of lactate rose in all forms of acidosis as well as the production of pyruvate. In the renal cortical tissue, the concentration of malate, pyruvate, and lactate rose. Alanine also rose except during anoxia. An important fall in cytosolic redox potential (NAD+/NADH lactate dehydrogenase) was observed, as well as a fall in mitochondrial redox (NAD+/NADH beta-hydroxybutyrate dehydrogenase). Lactate also accumulated in the liver and in the muscle. We propose that the kidney is unable to respond to lactic acidosis in terms of ammonia production and that this phenomenon is explained by transamination of pyruvate and glutamate into alanine and also by the observed fall in cytosolic redox potential. It is likely that renal gluconeogenesis is also inhibited and this is reflected by the rise in the concentration of malate in the kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗
PubMed1986

Renal tissue metabolism in the rat during chronic metabolic alkalosis: importance of glycolysis.

Chronic metabolic alkalosis was induced in rats drinking 0.3 M NaHCO3 and receiving 1 mg furosemide/100 g body weight per day intraperitoneally. Another group of animals received a potassium supplement in the form of 0.3 M KHCO3. In this group, hypokalemia did not develop and muscle potassium fell by only 18% versus 50% in those not receiving potassium. In vitro renal production of ammonia and uptake of glutamine fell by 40% with a decrease in the activity of glutaminase I and glutamate dehydrogenase. Activity of phosphofructokinase, a major enzyme of glycolysis, rose only in the kidney of animals receiving a potassium supplement. Fructose-1,6-diphosphatase fell as well as phosphoenolpyruvate carboxykinase. Malate dehydrogenase also fell. The activity of phosphofructokinase also rose in the liver, heart, and leg muscle. The major biochemical changes in the renal cortex were the following: glutamate, alpha-ketoglutarate, malate, lactate, pyruvate, alanine, aspartate, and citrate rose as well as calculated oxaloacetate. The concentration of intermediates like 2-phosphoglycerate, 3-phosphoglycerate, and glucose-6-phosphate fell. The cytosolic redox potential (NAD+/NADH) decreased. In addition to the fall in ammoniagenesis, it could be demonstrated in vitro that the renal tubules incubated with glutamine showed decreased glucose production and increased production of lactate and pyruvate. The concentration of lactate was elevated in all tissues examined including liver, heart, and leg muscle. This study confirms in the rat that decreased renal ammoniagenesis takes place following decreased uptake of glutamine in metabolic alkalosis. All other changes are accounted for by the process of increased glycolysis, which appears to take place in all tissues in metabolic alkalosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkalosis↗
PubMed1985

Net tubular secretion of bicarbonate by the alligator kidney. Antimammalian response to acetazolamide.

Net tubular secretion of bicarbonate by the alligator kidney was demonstrated during acute clearance experiments where the animals were infused with an isosmotic solution of one-half 5% mannitol and one-half 0.9% NaCl. Tubular secretion of bicarbonate averaged 3.38 mumoles/min in animals with a mean wt of 1.0 kg. During these experiments, mean tubular secretion of urate was 0.51 mumole/min and urinary ammonia excretion was 4.3 mumoles/min. Urinary pNH3 was high and ranged from 22,231 to 41,223 mm Hg X 10(-6). The administration of acetazolamide 25 mg/kg resulted in abolition of bicarbonate secretion, which was replaced by bicarbonate reabsorption. At the same time, the tubular secretion of urate fell by 70% and the excretion of ammonia fell by 77%. This is the first time that net tubular secretion of bicarbonate is demonstrated in a living animal. Acetazolamide has an antimammalian effect. It is proposed that the alligator that lives with a low plasma bicarbonate concentration (10 mM) possesses a kidney in which the renal tubular cells secrete bicarbonate in the tubular lumen and hydrogen at the peritubular site, in contrast to that which takes place in mammalia and other animal species.

Absorption↗
PubMed1985

Renal tubular biochemistry during acute and chronic metabolic alkalosis in the dog.

Acute metabolic alkalosis was induced in dogs by the infusion of sodium bicarbonate, 0.3 M. Chronic alkalosis was induced by chloride restriction and the administration of sodium bicarbonate and furosemide. In a third group of dogs, potassium was added to the regimen to prevent frank potassium depletion. Plasma bicarbonate ranged from 29.0 to 32.9 mM. In all three dog groups, renal ammoniagenesis fell by over 30%, which was consistent with a decrease in the renal uptake of glutamine. Glutamate was released in the renal vein and alanine production was decreased. Total production of ammonia was lowest in the animals given a potassium supplement where muscle potassium decreased much less than in the other chronic animals. Urinary ammonia excretion was very low in all three animal groups; this was related to an alkaline urine. However, this relationship was not entirely consistent and the low excretion of ammonia could also be related to decreased ammonia production by the renal tubular cell. In the renal cortical tissue (freeze-clamped), the concentration of glutamate did not change and that of alpha-ketoglutarate rose only in the animals supplemented with potassium. Malate rose in all groups. In all animals, renal tissue concentration of lactate and citrate rose while citrate excretion increased. We feel that glycolysis could play an important role in renal metabolism during acute and chronic metabolic alkalosis. We have proposed a unified theory to explain the metabolic changes that occur in lactate and citrate metabolism during metabolic alkalosis with a depressing effect on ammoniagenesis. Although citrate could be generated in the mitochondria from pyruvate, its oxidation is probably inhibited with exit and accumulation in the cytosol.

Acute Disease↗
PubMed1985

The metabolic response of the kidney to acute sodium lactate alkalosis.

In vivo studies were performed in the dog to verify if sodium lactate had an important effect on the metabolism of glutamine by the kidney. The animals were infused with 0.6 M sodium lactate to induce acute metabolic alkalosis with plasma bicarbonate of 29.7 mM. During these experiments, it was demonstrated that the renal uptake of glutamine increased by 46%, while the renal production of ammonia was unchanged. The renal production of alanine rose from 6.0 to 16.8 mumol/min. Plasma concentration of lactate increased from 1.3 to 19.2 mM, while that of pyruvate increased from 0.075 to 0.454 mM. In the renal tissue, alpha-ketoglutarate, malate, oxaloacetate, lactate, pyruvate, citrate, and alanine increased significantly. Similar changes were found in the liver and skeletal muscle. The observed changes are best described by transamination of pyruvate and glutamate under the influence of alanine aminotransferase (GPT). It can be calculated that this reaction was responsible for 76% of the production of ammonia from glutamine, the latter being necessary to provide glutamate for the synthesis of alanine. Dogs infused with 0.3 M sodium bicarbonate instead of sodium lactate with the same degree of acute metabolic alkalosis, showed a depression of 40% in the renal uptake of glutamine with a 38% decrease in renal ammoniagenesis and a 20% fall in the production of alanine. The present studies demonstrate that the production of ammonia from glutamine is not necessarily related to changes in acid-base balance, but may be associated with biochemical alterations related to the synthesis of alanine by the kidney.

Alanine↗
PubMed1984

Renal enzymes during experimental diabetes mellitus in the rat. Role of insulin, carbohydrate metabolism, and ketoacidosis.

The activities of various ammoniagenic, gluconeogenic, and glycolytic enzymes were measured in the renal cortex and also in the liver of rats made diabetic with streptozotocin. Five groups of animals were studied: normal, normoglycemic diabetic (insulin therapy), hyperglycemic, ketoacidotic, and ammonium chloride treated rats. Glutaminase I, glutamate dehydrogenase, glutamine synthetase, phosphoenolpyruvate carboxykinase (PEPCK), hexokinase, phosphofructokinase, fructose-1,6-diphosphatase, malate dehydrogenase, malic enzyme, and lactate dehydrogenase were measured. Renal glutaminase I activity rose during ketoacidosis and ammonium chloride acidosis. Glutamate dehydrogenase in the kidney rose only in ammonium chloride treated animals. Glutamine synthetase showed no particular variation. PEPCK rose in diabetic hyperglycemic animals and more so during ketoacidosis and ammonium chloride acidosis. It also rose in the liver of the diabetic animals. Hexokinase activity in the kidney rose in diabetic insulin-treated normoglycemic rats and also during ketoacidosis. The same pattern was observed in the liver of these diabetic rats. Renal and hepatic phosphofructokinase activities were elevated in all groups of experimental animals. Fructose-1,6-diphosphatase and malate dehydrogenase did not vary significantly in the kidney and the liver. Malic enzyme was lower in the kidney and liver of the hyperglycemic diabetic animals and also in the liver of the ketoacidotic rats. Lactate dehydrogenase fell slightly in the liver of diabetic hyperglycemic and NH4Cl acidotic animals. The present study indicates that glutaminase I is associated with the first step of increased renal ammoniagenesis during ketoacidosis. PEPCK activity is influenced both by hyperglycemia and ketoacidosis, acidosis playing an additional role. Insulin appears to prevent renal gluconeogenesis and to favour glycolysis. The latter would seem to remain operative in hyperglycemic and ketoacidotic diabetic animals.

Animals↗
PubMed1984

The lipid content of the diabetic kidney of the rat.

Rats were made diabetic by intravenous administration of streptozotocin, 100 mg/kg. Six groups of animals were studied: normal; animals given a supplement of 100% corn oil margarine; insulin-treated normoglycemic diabetic; hyperglycemic nonacidotic diabetic; ketoacidotic diabetic; and NH4Cl acidotic. The kidneys were removed from anesthetized animals. The renal cortex was separated from the medulla, freeze-clamped, and homogenized. Total lipids were extracted and measured gravimetrically. Lipid fractions were determined by thin-layer chromatography. Fatty acids of triacylglycerols and of phospholipids were analyzed by gas chromatography. Plasma triacylglycerols were elevated in hyperglycemic nonacidotic rats and more so in ketoacidotic animals. Total kidney lipids were 18% higher in nonacidotic hyperglycemic rats and 56% higher in ketoacidotic diabetic rats. This was due to accumulation of triacylglycerols while the phospholipid and cholesterol fractions did not change. Examination of long-chain fatty acids of kidney cortex triacylglycerols revealed that palmitate rose in a significant fashion while linoleate fell. This pattern was similar in all three groups of diabetic animals. The present data characterize the lipid content of the experimental rat diabetic kidney. They establish that the accumulation of lipids in the renal cortex during diabetes is related to triacyclgycerols and their palmitate content. Our study also provides a clear profile of plasma triacylglycerols during diabetes mellitus in the rat.

Ammonium Chloride↗
PubMed1984

Metabolic machinery of the alligator kidney.

Crocodilians such as caimans and alligators are uricotelic and ammoniotelic animals. They are carnivorous but they excrete ammonium ions in an alkaline urine. The metabolic organization of the kidney of the Mississippi alligator was studied by measuring the renal metabolite profile, the activities of enzymes, and the behavior of kidney tubules in vitro. The liver and tail muscle were also studied. Both awake and anesthetized animals were in a state of low plasma bicarbonate and low blood pH with high plasma lactate concentration. This did not prevent the excretion of an alkaline urine (pH 7.76). alpha-Ketoglutarate was low in all three tissues and lactate was high. Glutamate concentration and glutamate dehydrogenase activity were highest in the kidney with a low equilibrium constant for alanine aminotransferase (KGPT). Glutaminase I was found only in the kidney. It could not be detected in liver or muscle. Glutamine synthetase was found only in the liver. Phosphoenolpyruvate carboxykinase (PEPCK) was present in both liver and kidney. Alanine aminotransferase and malic enzyme showed high activity in the kidney but were inconspicuous in liver and muscle. Malate dehydrogenase and lactate dehydrogenase were present in all three tissues. Renal tubules incubated with glutamine and alanine were ammoniagenic and gluconeogenic. Lactate was gluconeogenic. Enzyme activities were measured at both 30 and 37 degrees C. The studies on renal tubules were also performed at these two temperatures. Temperature had little effect on the data including acid-base values in the blood. Our findings demonstrate that the kidney of the alligator is perfectly equipped for various metabolic functions and especially for ammoniagenesis and gluconeogenesis.

Acid-Base Equilibrium↗
PubMed1983

Normal urate transport into erythrocytes in familial renal hypouricemia and in the Dalmatian dog.

It has been hypothesized that humans with familial renal hypouricemia may have a generalized defect of urate transport across cell membranes due to the genetic deletion of a specific carrier, a defect similar to that reported in the Dalmatian dog. In this study the transport of urate labelled with carbon 14 by the erythrocytes of four patients with familial renal hypouricemia was identical to that of five healthy controls. The addition of hypoxanthine to the incubation medium inhibited the transport to a similar extent in the two groups of patients, demonstrating the presence of a carrier specific for urate. This carrier was also found to be present in the erythrocytes of Dalmatian and mongrel dogs. Thus, the renal anomaly causing the hypouricemia in both species is not related to a generalized deletion of a urate-transporting protein on cell membranes.

Animals↗
PubMed1983

Importance of medullary events in ammonium excretion: studies in acute respiratory and acute metabolic acidosis.

The renal medulla can play an important role in acid excretion by modulating both hydrogen ion secretion in the medullary collecting duct and the medullary PNH3. The purpose of these experiments was to characterize the intrarenal events associated with ammonium excretion in acute acidosis. Cortical events were monitored in two ways: first, the rates of glutamine extraction and ammoniagenesis were assessed by measuring arteriovenous differences and the rate of renal blood flow; second, the biochemical response of the ammoniagenesis pathway was examined by measuring glutamate and 2-oxoglutarate, key renal cortical metabolites in this pathway. There were no significant differences noted in any of these cortical parameters between acute respiratory and metabolic acidosis. Despite a comparable twofold rise in ammonium excretion in both cases, the urine pH, PNH3, and the urine minus blood PCO2 difference (U-B PCO2) were lower during acute hypercapnia. In these experiments, the urine PCO2 was 34 mmHg (1 mmHg = 133.322 Pa) lower than that of the blood during acute respiratory acidosis while the U-B PCO2 was 5 +/- 3 mmHg in acute metabolic acidosis. Thus there were significant differences in medullary events during these two conditions. Although the urine pH is critical in determining ammonium excretion in certain circumstances, these results suggest that regional variations in the medullary PNH3 can modify this relationship.

Acidosis↗
PubMed1983

Bicarbonaturic effect of acetazolamide in the dog: the influence of graded volume expansion.

Studies were performed in anesthetized dogs to characterize the effect of a progressive volume expansion on the acetazolamide-induced bicarbonaturia. A closed system with urine reinfusion was used in all these experiments. In normovolemic dogs, 24% of the filtered bicarbonate was excreted into the urine while this value reached 62% when a 10% expansion was superimposed on a continuous infusion of acetazolamide. When a single dose of acetazolamide was given, fractional bicarbonate excretion increased from 21% in normovolemic dogs to 46% during 10% expansion. Without acetazolamide administration, 13% of the filtered bicarbonate was excreted during a 10% expansion. The continuous infusion of acetazolamide in normovolemic dogs increased fractional bicarbonate excretion in a progressive fashion, from 25 to 40%. This study shows that an acute volume expansion potentiates markedly the bicarbonaturic effect of acetazolamide, fractional bicarbonate excretion exceeding by far the simple additive effect of acetazolamide and expansion. We speculate that volume expansion might prevent a compensatory rise in acetazolamide-insensitive bicarbonate reabsorption in sites other than the superficial proximal convoluted tubules.

Acetazolamide↗
PubMed1983

Decreased distal acidification in acute hypercapnia in the dog.

The present studies evaluate the effect of acute hypercapnia on distal nephron H+ secretion (DNH+S) in vivo by means of the urine-blood PCO2 difference (U-B PCO2) in alkaline urine. Bicarbonaturia was induced by either a sodium bicarbonate infusion or L-lysine administration. Our results demonstrate that the U-B PCO2, as a function of the urinary bicarbonate concentration, was significantly lower during acute respiratory acidosis; this effect was not dependent on changes in glomerular filtration rate and/or fractional excretion of sodium, potassium, and chloride. Infusion of the sodium salts of sulfate, a nonreabsorbable anion, did not correct the diminished U-B PCO2. Amiloride caused the U-B PCO2 to fall in normocapnic dogs but not in hypercapnic dogs. When hypercapnia was superimposed in dogs with extracellular fluid volume contraction, there were no changes in the U-B PCO2. This study indicates that acute hypercapnia in the intact dog decreases DNH+S and is compatible with an effect of hypercapnia on the voltage-dependent component of urine acidification. The mechanism appears to be direct rather than secondary to factors that influence the rate of sodium delivery to the distal nephron.

Acidosis, Respiratory↗
PubMed1983

Metabolism and transport of L-glutamine and L-alanine by renal tubules of chickens.

The metabolism and cellular transport of 1 and 5 mM glutamine (Gln) and alanine (Ala) and the metabolism of lactate (Lac) by renal tubular fragments of normal and chronically acidotic chickens were studied. The tubules were prepared by the collagenase digestion procedure and incubated for 0-60 min with or without substrates. Acidosis increased 1 mM Gln utilization from 1.14 to 1.74 and 1 mM Ala from 1.55 to 2.92 mumol X min-1 X g wet wt-1. Gluconeogenesis increased from 0.29 to 0.59 (Gln) and 0.44 to 1.06 (Ala), while ammoniagenesis rose from 2.19 to 3.24 (Gln) and 1.54 to 2.56 (Ala) mumol X min-1 X g-1. In contrast, Lac uptake (2.71 mumol X min-1 X g-1) and gluconeogenesis from Lac (1.05 mumol X min-1 X g-1), which equalled or exceeded the values observed with Gln or Ala in normal rats, were unchanged by acidosis. These data suggest 1) that acidosis increases gluconeogenesis from Gln and Ala by accelerating the glutamate deamination process, and 2) that the glutamate originating from glutamine and alanine are segregated in two different pools within the mitochondria with different access to glutamate dehydrogenase activity. Net cellular uptake of Gln was greater in acidotic chicken tubules, establishing an intracellular concentration of 4.5 in acidotic vs. 3.0 mM in normal chickens when 1 mM Gln was used in the incubation medium. In contrast, 1 mM alanine uptake was not modified by acidosis, greater intracellular metabolism lowering the cellular concentration of this amino acid. These observations suggest that the cellular transport of glutamine but not that of alanine is increased in tubular fragments of acidotic chickens.

Acidosis, Respiratory↗
PubMed1983

The treatment of hypertension with indapamide alone or in combination with other drugs.

Twenty-six patients (average age 50 years) with essential hypertension were treated for 4 months with 2.5 mg indapamide per day, alone or in combination with other drugs. Before treatment, the average blood pressure was 208/128 mmHg, and each patient had undergone at least 6-months' therapy with hydrochlorothiazide alone (6 patients), in combination with reserpine (11 patients), or with methyldopa, hydralazine, propranolol, metoprolol or guanethidine (9 patients). Indapamide was prescribed to replace hydrochlorothiazide, the other antihypertensive drugs being continued in those patients receiving combination therapy. The average supine blood pressure decreased from 148/93 mmHg with hydrochlorothiazide to 143/92 mmHg during an intermediate 4-week placebo period, and to 135/86 mmHg with indapamide. Effects on blood pressure and all other parameters were the same, whether indapamide was used alone or in combination with other drugs. Serum potassium levels at the end of treatment averaged 3.6 mmol/l, a value similar to that obtained with hydrochlorothiazide. Plasma bicarbonate was unchanged (27.5 mmol/l), serum uric acid averaged 7.4 mg/dl, and renal function remained normal. Other parameters showing no change included blood glucose, cholesterol, triglycerides, total bilirubin, transaminases, platelets, etc. All the patients reported a sensation of well-being during treatment with indapamide; this drug shows clinical and biochemical effects similar to those of the thiazide-type diuretics.

Adrenergic beta-Antagonists↗