On the mode of action of diuretics II effects of ethacrynic acid on renal oxygen consumption and tubular sodium reabsorption in dogs

Wolf, Karsten D.; Bieg, A.; Fülgraff, G.

doi:10.1016/0014-2999(69)90103-4

Cited by 22 publications

(6 citation statements)

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“…13 and 73 and the present study), since our experience is that this anesthetic tends to inhibit T Na ϩ. Estimates of basal percent renal V O 2 derived from studies of dogs in a natriuretic state are also likely to be overestimates(9,60,66,81). If we…”

mentioning

confidence: 57%

“…We identified 10 publications that presented estimates of basal percent renal V O 2 determined by extrapolation to the ordinal intercept of the relationship between GFR or T Na ϩ and V O 2 total (i.e., when GFR or T Na ϩ ϭ 0) in experiments in which no specific interventions were applied to alter GFR or T Na ϩ. In anesthetized dogs (16,34,58,72,81) and rats (80) and unanesthetized humans (2,3,33,48), estimates of basal percent renal V O 2 ranged from 0% to 43.4% (Table 1).…”

Section: Basal Percent Renal V Omentioning

confidence: 99%

“…We identified 12 publications reporting estimates of basal percent renal V O 2 derived from an extrapolation of the relationship between GFR or T Na ϩ and V O 2 total from experiments in which specific treatments were applied to alter GFR or T Na ϩ. These treatments included progressive hemorrhage (30,73), suprarenal aortic constriction (60), administration of diuretic agents (9,30,49,79,81), expansion of extracellular fluid volume (12,57), inhibition of ouabain-sensitive Na ϩ -K ϩ -ATPase (9), halothane inhalation (70), and chronic recovery from ischemia-reperfusion injury (52). These estimates of basal percent renal V O 2 , from studies in anesthetized dogs, rabbits, and rats, ranged from 15% to 64.6% (Table 1).…”

Section: Basal Percent Renal V Omentioning

confidence: 99%

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Basal renal O₂consumption and the efficiency of O₂utilization for Na⁺reabsorption

Evans

Harrop

Ngo

et al. 2014

American Journal of Physiology-Renal Physiology

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We examined how the presence of a fixed level of basal renal O2 consumption (Vo2(basal); O2 used for processes independent of Na(+) transport) confounds the utility of the ratio of Na(+) reabsorption (TNa(+)) to total renal Vo2 (Vo2(total)) as an index of the efficiency of O2 utilization for TNa(+). We performed a systematic review and additional experiments in anesthetized rabbits to obtain the best possible estimate of the fractional contribution of Vo2(basal) to Vo2(total) under physiological conditions (basal percent renal Vo2). Estimates of basal percent renal Vo2 from 24 studies varied from 0% to 81.5%. Basal percent renal Vo2 varied with the fractional excretion of Na(+) (FENa(+)) in the 14 studies in which FENa(+) was measured under control conditions. Linear regression analysis predicted a basal percent renal Vo2 of 12.7-16.5% when FENa(+) = 1% (r(2) = 0.48, P = 0.001). Experimentally induced changes in TNa(+) altered TNa(+)/Vo2(total) in a manner consistent with theoretical predictions. We conclude that, because Vo2(basal) represents a significant proportion of Vo2(total), TNa(+)/Vo2(total) can change markedly when TNa(+) itself changes. Therefore, caution should be taken when TNa(+)/Vo2(total) is interpreted as a measure of the efficiency of O2 utilization for TNa(+), particularly under experimental conditions where TNa(+) or Vo2(total) changes.

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mentioning

confidence: 57%

Section: Basal Percent Renal V Omentioning

confidence: 99%

Section: Basal Percent Renal V Omentioning

confidence: 99%

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Basal renal O₂consumption and the efficiency of O₂utilization for Na⁺reabsorption

Evans

Harrop

Ngo

et al. 2014

American Journal of Physiology-Renal Physiology

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“…However, this correlation has less strength than with oxygen consumption, because drugs, such as dopamine and diuretics, change the ratio between oxygen consumption and sodium reabsorption. 16,17 Pigs are commonly used in renal functional imaging studies for renal size and availability purpose. The cortex is 1 cm thick, therefore, there is no need for partial volume correction, especially with carbon-11 acetate, which provides a good spatial resolution.…”

Section: Discussionmentioning

confidence: 99%

Validation of Renal Oxidative Metabolism Measurement by Positron-Emission Tomography

Juillard

Lemoine²,

Janier³

et al. 2007

Hypertension

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Abstract-Either in research or in clinical practice, the exploration of renal oxidative metabolism is limited by the lack of noninvasive measurement. Positron-emission tomography using carbon-11 acetate may estimate tissue oxidative metabolism by measuring acetate turnover in the Krebs cycle. Although extensively studied in cardiology, this method has never been validated for renal oxidative metabolism measurement. The aim of this study is the validation of acetate turnover compared with the invasive renal oxygen consumption measurement. Renal oxygen consumption and tubular sodium reabsorption were measured invasively in 10 anesthetized pigs. Simultaneously, acetate turnover was estimated by the clearance of carbon-11 acetate in the renal cortex, after a 166-MBq injection of carbon-11 acetate. Renal oxidative metabolism was measured under various conditions induced by mechanical and pharmacological interventions. Renal oxygen consumption and acetate turnover varied on a wide range from 0.05 to 0.29 mmol min Ϫ1 (Ͼ5-fold) and from 0.025 to 0.188 minutes Ϫ1 (Ͼ7-fold), respectively. Acetate turnover was very significantly correlated with renal oxygen consumption (PϽ0.0001; Rϭ0.82) and tubular sodium reabsorption (Pϭ0.001; Rϭ0.67). This study demonstrates that acetate turnover measures renal oxidative metabolism noninvasively and quantitatively, consistent with changes in tubular sodium reabsorption. This method may be applied to assess oxidative metabolism in animal models and in humans. Key Words: cell respiration Ⅲ kidney Ⅲ positron-emission tomography Ⅲ carbon-11 acetate Ⅲ oxygen consumption K idneys have the highest basal oxidative metabolism, representing 10% of basal body metabolism for 1% of the body weight. 1 This very high oxidative metabolism is mainly involved in sodium reabsorption, and changes in renal oxidative metabolism correlate closely with changes in sodium reabsorption. 2,3 It is, therefore, most likely that renal oxidative metabolism could be changed significantly in chronic renal diseases, ischemic nephropathy, or by drugs, such as diuretics.Until now, changes in oxidative were studied by the measurement of oxygen consumption in isolated tubules or by the direct measurement of renal oxygen consumption using arteriovenous difference. 3 Those methods are invasive and cannot be applied in humans. Therefore, the exploration of renal oxidative metabolism changes induced during human diseases is limited.Positron-emission tomography (PET) is an imaging modality that provides quantitative and noninvasive measurements of functional parameters. After carbon-11-labeled acetate intravenous injection, renal cells extract acetate from the blood. Then, acetate is consumed in the Krebs cycle, depending on the intensity of oxidative metabolism, and is rejected in blood as 11 CO 2 . 4 Using this principle, acetate turnover measurement by PET has been extensively used in cardiology to evaluate heart viability. 5 Shreve et al 6 showed that renal acetate turnover measured by PET was markedly changed in human renal ...

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“…(Goldberg, 1966;Laragh, Cannon, Stason & Heinemann, 1966;Seldin, Eknoyan, Suki & Rector, 1966;Aukland, Johannesen & Kiil, 1969;Davis, 1970). Its mode of action, in terms of interference with metabolic processes and ion transporting systems, is more uncertain (Wolf, Bieg & Fulgraff, 1969;Duggan & Noll, 1972;Landon & Fitzpatrick, 1972 745 Contreras, 1972;Inagaki et al 1973;Lie, Sejersted, Raeder & Kiil, 1974). Conversely, there is general agreement that at both cortical and medullary levels ouabain acts by the inhibition of Na-K-activated ATPase (Nelson & Nechay, 1970;Allen, Martinez-Maldonado, Eknoyan, Suki & Schwartz, 1971;Torretti, Hendler, Weinstein, Longnecker & Epstein, 1972) but doubt as to whether, in the rat, the ascending limb of Henle's loop is a major site of diuretic action (Streider, Khuri, Weiderholt & Giebisch, 1974).…”

Section: Introductionmentioning

confidence: 99%

The effects of ouabain and ethacrynic acid on the intracellular sodium and potassium concentrations in renal medullary slices incubated in cold potassium‐free ringer solution and re‐incubated at 37 degrees C in the presence of external potassium.

Law¹

1976

The Journal of Physiology

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SUMMARY1. The cells in slices cut from the renal outer medulla of normally hydrated adult rats were loaded with Na and depleted of K by incubation for up to 100 min in cold iso-osmolal K-free Ringer containing 180 mM-Na. There was a continuous net cellular water loss during this time; an inverse linear relationship existed between water content and intracellular Na concentration.2. The original intracellular Na and K concentrations were restored following 60 min re-incubation in warm Ringer (370 C) containing 5*9 mM-K. Restoration of cellular water content was incomplete after re-incubation for up to 120 min.3. During incubation in cold K-free Ringer the presence of 1 mm ouabain did not affect cellular Na uptake or K and water loss. Ethacrynic acid, 1 mm, completely blocked cellular Na uptake and water loss, without affecting the intracellular K concentration at 100 min. When ouabain and ethacrynic acid were present together water loss was also prevented but intracellular Na concentration rose slightly by 100 min.4. During re-incubation in warm K-containing Ringer 1 mm ouabain inhibited Na extrusion completely for up to 60 min while only partially preventing K uptake and further depressing the level of cellular hydration. Ouabain in the presence of 1 mm ethacrynic acid had similar effects on intracellular Na and K concentrations, but raised the level of intracellular water above that of cells in control slices.5. Ethacrynic acid alone, 1 mm, did not interfere with Na extrusion or K uptake, but also raised intracellular water above control values.6. The results obtained are discussed in relation to (a) the nature of the 27-2

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On the mode of action of diuretics II effects of ethacrynic acid on renal oxygen consumption and tubular sodium reabsorption in dogs

Cited by 22 publications

References 8 publications

Basal renal O₂consumption and the efficiency of O₂utilization for Na⁺reabsorption

Basal renal O₂consumption and the efficiency of O₂utilization for Na⁺reabsorption

Validation of Renal Oxidative Metabolism Measurement by Positron-Emission Tomography

The effects of ouabain and ethacrynic acid on the intracellular sodium and potassium concentrations in renal medullary slices incubated in cold potassium‐free ringer solution and re‐incubated at 37 degrees C in the presence of external potassium.

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On the mode of action of diuretics II effects of ethacrynic acid on renal oxygen consumption and tubular sodium reabsorption in dogs

Cited by 22 publications

References 8 publications

Basal renal O2consumption and the efficiency of O2utilization for Na+reabsorption

Basal renal O2consumption and the efficiency of O2utilization for Na+reabsorption

Validation of Renal Oxidative Metabolism Measurement by Positron-Emission Tomography

The effects of ouabain and ethacrynic acid on the intracellular sodium and potassium concentrations in renal medullary slices incubated in cold potassium‐free ringer solution and re‐incubated at 37 degrees C in the presence of external potassium.

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Basal renal O₂consumption and the efficiency of O₂utilization for Na⁺reabsorption

Basal renal O₂consumption and the efficiency of O₂utilization for Na⁺reabsorption