Effect of Chronic Metabolic Acidosis on Renal Growth and Renal Sodium Handling in Uninephrectomized Rats

Menegon, Leonardo Fantinato; Figueiredo, José Francisco; Gontijo, José Antônio Rocha

doi:10.3109/08860229909066966

Cited by 9 publications

(10 citation statements)

References 26 publications

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“…In this regard, we have previously shown that chronic metabolic acidosis, caused by NH 4 Cl feeding, leads to nephron hypertrophy and to a decreased watersalt reabsorption by the kidneys [1,25,26]. Since renal ion tubule transport is highly dependent on mitochondrial energy and because mitochondria have been implicated in a variety of metabolic disorders, we examined mitochondrial energy-linked functions in chronic metabolic acidotic rats.…”

Section: Discussionmentioning

confidence: 99%

Effects of NH4Cl-induced systemic metabolic acidosis on kidney mitochondrial coupling and calcium transport in rats

Bento

Fagian

Vercesi

et al. 2007

Nephrology Dialysis Transplantation

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Background. We have previously shown that chronic metabolic acidosis, induced in rats by NH 4 Cl feeding, leads to nephron hypertrophy and to a decreased water-salt reabsorption by the kidneys. Since mitochondria are the main source of metabolic energy that drives ion transport in kidney tubules, we examined energy-linked functions (respiration, electrochemical membrane potential and coupling between respiration and ADP phosphorylation) in mitochondria isolated from rat kidney and liver at 48 h after metabolic acidosis induced by NH 4 Cl. Methods. Mitochondria isolated from the kidneys and liver of metabolic acidotic rats, induced by NH 4 Cl, was used to study of the oxygen consumption by Clarktype electrode, mitochondrial electrical transmembrane potential estimated by the safranine O method and the variations in free medium Ca 2+ concentrations examined by absorbance spectrum of Arsenazo III set at the 675-685 nm wavelength pair. Results. Whole kidney and liver mitochondria isolated from 48 h acidotic rats presented higher resting respiration, lower respiratory control and a lower ADP/O ratio than controls. These differences in mitochondrial coupling, between respiration and oxidative phosphorylation (ATP synthesis), were totally corrected when experiments were carried out in the presence of carboxyatractyloside, GDP and BSA, indicating that mitochondrial uncoupling proteins are more active in acidotic rat kidneys. Interestingly, determination of Ca 2þ transport demonstrated a faster rate of initial Ca 2þ uptake by acidotic kidney mitochondria, which resulted in a lower concentration of extra-mitochondrial Ca 2þ under steady-state conditions (Ca 2þ set point) when compared with control mitochondria.In contrast, there were no significant differences in the rates of Na þ or ruthenium red induced Ca 2þ efflux. Conclusions. We suggest that the mild uncoupling and higher Ca 2þ accumulation represents an adaptation of the mitochondria to cope with conditions of oxidative stress and high cytosolic Ca 2þ , which are associated with a decreased efficiency of oxidative phosphorylation that may explain, at least in part, the striking natriuresis observed under chronic acidosis. Finally, there were no changes in Ca 2þ transport or coupling in liver mitochondria isolated from the acidotic rats.

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Section: Discussionmentioning

confidence: 99%

Effects of NH4Cl-induced systemic metabolic acidosis on kidney mitochondrial coupling and calcium transport in rats

Bento

Fagian

Vercesi

et al. 2007

Nephrology Dialysis Transplantation

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“…Fractional sodium (FENa + ) and potassium (FEK + ) excretions were calculated as CNa + / CCr and CK + /CCr, respectively, where CNa + and CK + are the ion clearances and CCr is the creatinine clearance. The fractional proximal (FEPNa + ) and post-proximal (FEPPNa + ) sodium excretions were calculated as CLi + / CCr x 100 and CNa + /CLI + x 100, respectively (18,19). Changes in fractional excretion were estimated using the values from sham-operated rats.…”

Section: Statistics and Calculationsmentioning

confidence: 99%

Effect of inhibition of nitric oxide synthase on blood pressure and renal sodium handling in renal denervated rats

Xavier

Magalhães

Gontijo

2000

Braz J Med Biol Res

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The role of sympathetic nerve activity in the changes in arterial blood pressure and renal function caused by the chronic administration of N Gnitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, was examined in sham and bilaterally renal denervated rats. Several studies have demonstrated that sympathetic nerve activity is elevated acutely after L-NAME administration. To evaluate the role of renal nerve activity in L-NAME-induced hypertension, we compared the blood pressure response in four groups (N = 10 each) of male WistarHannover rats weighing 200 to 250 g: 1) sham-operated vehicle-treated, 2) sham-operated L-NAME-treated, 3) denervated vehicle-treated, and 4) denervated L-NAME-treated rats. After renal denervation or sham surgery, one control week was followed by three weeks of oral administration of L-NAME by gavage. Arterial pressure was measured weekly in conscious rats by a tail-cuff method and renal function tests were performed in individual metabolic cages 0, 7, 14 and 21 days after the beginning of L-NAME administration. L-NAME (60 mg kg -1 day -1 ) progressively increased arterial pressure from 108 ± 6.0 to 149 ± 12 mmHg (P<0.05) in the sham-operated group by the third week of treatment which was accompanied by a fall in creatinine clearance from 336 ± 18 to 222 ± 59 µl min -1 100 g body weight -1 (P<0.05) and a rise in fractional urinary sodium excretion from 0.2 ± 0.04 to 1.62 ± 0.35% (P<0.05) and in sodium post-proximal fractional excretion from 0.54 ± 0.09 to 4.7 ± 0.86% (P<0.05). The development of hypertension was significantly delayed and attenuated in denervated L-NAME-treated rats. This was accompanied by a striking additional increase in fractional renal sodium and potassium excretion from 0.2 ± 0.04 to 4.5 ± 1.6% and from 0.1 ± 0.015 to 1.21 ± 0.37%, respectively, and an enhanced postproximal sodium excretion compared to the sham-operated group. These differences occurred despite an unchanged creatinine clearance and Na + filtered load. These results suggest that bilateral renal denervation delayed and attenuated the L-NAME-induced hypertension by promoting an additional decrease in tubule sodium reabsorption in the postproximal segments of nephrons. Much of the hypertension caused by chronic NO synthesis inhibition is thus dependent on renal nerve activity. Correspondence

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“…39 Rarely liver disease can result in prerenal azotemia with an elevated FeNa because of sodium bicarbonate wasting from alkalosis 30 or alternatively because of loss of urea production that is necessary for water reabsorption and urine concentration. 101 Similarly bicarbonate conservation in acute (but not chronic) respiratory acidosis may cause a false depression through sodium bicarbonate conservation and generation 31 while metabolic acidosis has also been associated with an elevated FeNa regardless of volume 32,33 perhaps through hypercalcemia and hypomagnesemia may also interfere with tubular ability to conserve sodium even in the presence of hypovolemia. 40 Extremes of age both young and old can affect both sodium excretion.…”

Section: Ureamentioning

confidence: 99%

“…Similarly, chronic (but not acute) respiratory acidosis is associated with a decrease in FeNa because of sodium bicarbonate generation and conservation by the tubules. 32 Chronic metabolic acidosis may also result in sodium wasting, 33,34 presumably because of a different mechanism where acidosis may disrupt active transport. Surprisingly, while use of diuretics are well known to make the FeNa unreliable, [36][37][38][39] other drugs, such as amphotericin, that are known to cause proximal tubular damage may not.…”

Section: Fenamentioning

confidence: 99%

“…24 or tubular function [25][26][27][28][29] which can result in an altered renal handling of sodium. [30][31][32][33][34][35][36]101 Surprisingly, while use of diuretics are well known to make the FeNa unreliable, [35][36][37][38] other drugs, such as amphotericin, that are known to cause proximal tubular damage may not. 39 Rarely liver disease can result in prerenal azotemia with an elevated FeNa because of sodium bicarbonate wasting from alkalosis 30 or alternatively because of loss of urea production that is necessary for water reabsorption and urine concentration.…”

Section: Ureamentioning

confidence: 99%

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Toward the optimal clinical use of the fraction excretion of solutes in oliguric azotemia

et al. 2010

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While the fractional excretion of solutes have long been considered excellent research tools to investigate tubular physiology, their clinical use has become common over the last 40 years in the diagnoses of many disorders; however, none have reached the clinical utility of the fractional excretion of sodium in the ability to distinguish pre-renal azotemia from acute tubular necrosis. Nevertheless, there are many drugs and medical conditions that interfere with that utility and recently other solutes, including urea, uric acid and lithium, have been recently investigated to improve the diagnostic ability in clinical situations where the fractional excretion of sodium is known to be unreliable. We review the tubular physiology of these solutes and show how the differences in tubular physiology might be exploited to develop a strategy for their optimal clinical use.

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Effect of Chronic Metabolic Acidosis on Renal Growth and Renal Sodium Handling in Uninephrectomized Rats

Abstract: ABSTRACT

Cited by 9 publications

References 26 publications

Effects of NH4Cl-induced systemic metabolic acidosis on kidney mitochondrial coupling and calcium transport in rats

Effects of NH4Cl-induced systemic metabolic acidosis on kidney mitochondrial coupling and calcium transport in rats

Effect of inhibition of nitric oxide synthase on blood pressure and renal sodium handling in renal denervated rats

Toward the optimal clinical use of the fraction excretion of solutes in oliguric azotemia

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