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PubMed1998

The effects of diuresis on the pharmacokinetics of the loop diuretics furosemide and torsemide in patients with heart failure.

PURPOSE: To evaluate the pharmacokinetics of furosemide and torsemide before and after diuresis in patients presenting with marked fluid overload. SUBJECTS AND METHODS: We studied 44 patients with New York Heart Association class III or IV heart failure, ejection fraction < or =40%, and an estimated excess fluid body weight > or =6.8 kg. Oral furosemide or torsemide was administered before and after diuresis. Pharmacokinetic parameters were assessed before and after diuresis. RESULTS: Following diuresis, maximum plasma concentration increased from 11.0+/-5.0 microg/mL to 13.9+/-6.8 with torsemide (P <0.05) and from 3.1< or =1.5 to 3.9+/-1.9 with furosemide (P=0.16). Maximum concentration increased by more than 30% in only one third of the patients. Total absorption (by area under the curve method) increased 6% among patients on torsemide (P=0.38) and 7% among patients on furosemide (P=0.63) and increased >30% in only 1 torsemide and 2 furosemide patients. The time to maximum concentration decreased from 1.40+/-.82 h to 0.81+/-0.36 with torsemide (P <0.01). There were no differences between furosemide and torsemide in the effects of edema on absorption. CONCLUSION: Marked diuresis altered the pharmacokinetics of both furosemide and torsemide in only a small percentage of patients. The use of adequate doses of oral diuretics in edematous patients may be successful, thereby permitting home treatment with oral diuretics and avoiding the cost of hospitalizations or home intravenous administration services.

Aged↗

PubMed1997

Increased toxicity of high-dose furosemide versus low-dose dopamine in the treatment of refractory congestive heart failure.

OBJECTIVE: To evaluate the safety and efficacy of low-dose dopamine, high-dose furosemide, and their combination in the treatment of refractory congestive heart failure. METHODS: Twenty consecutive patients with refractory congestive heart failure were randomized to receive intravenous low-dose (4 micrograms/kg/min) dopamine combined with low-dose (80 mg/day) oral furosemide (group A; n = 7), intravenous low-dose dopamine with medium-dose furosemide (5 mg/kg/day through continuous intravenous administration; group B; n = 7), or high-dose furosemide (10 mg/kg/day through continuous intravenous administration; group C; n = 6). RESULTS: The three groups showed similar improvement in signs and symptoms of congestive heart failure, urinary output (2506 +/- 671 ml/24 hr, mean +/- SD) and weight loss (3.3 +/- 2.3 kg) after 72 hours of therapy. Mean arterial blood pressure (MAP) decreased by 14% +/- 8% and 15% +/- 6% in groups B and C, respectively, but increased by 4% +/- 15% in group A (p = 0.017). Renal function deteriorated significantly in groups B and C: creatinine clearance decreased by 41% +/- 23% and 42% +/- 23%, respectively, but increased by 14% +/- 35% in group A (p = 0.0074). MAP decrease was positively correlated with the decrease in creatinine clearance (r = 0.7; p = 0.0007). Patients in group B and C had more hypokalemia than group A. Two patients in group C sustained acute oliguric renal failure and one patient in group B died suddenly while sustaining severe hypokalemia. CONCLUSION: Combined low-dose intravenous dopamine and oral furosemide have similar efficacy but induce less renal impairment and hypokalemia than higher doses of intravenous furosemide taken either alone or with low-dose dopamine. The renal impairment induced by intravenous furosemide is probably related to its hypotensive effect in patients with refractory congestive heart failure.

Acute Kidney Injury↗

PubMedDate not supplied

High-performance liquid chromatography-mass spectrometric analysis of furosemide in plasma and its use in pharmacokinetic studies.

This study presents a rapid, specific and sensitive high-performance liquid chromatography-mass spectrometric (LC-MS) assay for the determination of furosemide in human plasma using diclofenac as an internal standard (IS). Both compounds were extracted from human plasma with ethyl acetate at pH 1 and were chromatographed using Shim-Pack GLC-CN column and a mobile phase consisting of acetonitrile and 20 mM ammonium acetate buffer solution pH 7, 4:1 (v/v) at a flow rate 1 ml min(-1). Furosemide and IS were detected by mass spectrometer operated in the negative single ion monitoring mode using APCI as an ionization process at m/z 329.2 and 294.1, respectively. The assay linearity of furosemide was confirmed over the range 50-2,000 ng ml(-1). Detection limit for furosemide in plasma was 10 ng ml(-1). The selected concentration range corresponds well with the plasma concentrations of furosemide for pharmacokinetic study. Intraday and interday relative standard deviations were 1.3-4.7 and 2.7-11.5%, respectively. The extraction recovery percentages of furosemide and IS from plasma were in the range 89.3-97.1%. The developed LC-MS procedure was applied for the determination of the pharmacokinetic parameters of furosemide after an oral administration of tablet formulation (40 mg) to two healthy male volunteers. The calculated parameters were in good agreement with the reported values.

Adult↗

PubMed1978

Pharmacokinetic disposition and protein binding of furosemide in newborn infants.

Using a one-compartment model, the pharmacokinetic disposition of furosemide was studied in eight premature and term neonates with fluid overload. Following a single intravenous injection of furosemide (1 to 1.5 mg/kg), multiple blood samples were obtained from a heelstick or an arterial catheter and analyzed for furosemide by gas liquid chromatography. The mean (+/- SE) apparent volume of distribution was 829.2 +/- 118.9 ml/kg; t1/2 was 7.7 +/- 1.0 hour; elimination rate constant was 0.102 +/- 0.013/hour and plasma clearance was 81.61 +/- 14.98 ml/kg/hour. Compared to the disposition of furosemide in normal adults. AVd is almost fourfold greater in the neonate with an eightfold prolongation in plasma t1/2, an eightfold decrease in Ke1, and a twofold decrease in plasma clearance. Neither gestational and postnatal age nor birth weight correlated with the pharmacokinetic variables. No significant change in reserve bilirubin-binding capacity after an intravenous dose of furosemide was noted. Slow elimination of furosemide may partly explain the prolonged diuretic and saluretic effect of furosemide in the neonate.

Bilirubin↗

PubMed1980

Pharmacology of furosemide in the premature newborn infant.

The pharmacokinetic parameters of furosemide were measured in 14 premature newborn infants, one to 20 days of age, and in 12 older infants, aged one to 4 months, following a single intravenous dose of 1 mg/kg of furosemide. Furosemide levels were determined by a high pressure liquid chromatographic method which required 3 microliter of plasma. The volume of distributuion for furosemide was calculated to be 0.24 +/- 0.03 l/kg (mean +/- SE) in all infants studied, regardless of postnatal age. The half-life in the first three weeks of life was found to be 19.9 +/- 3.0 hours. Thus, the half-life of furosemide in the premature infant is considerably longer than in adults or older children, but the volume of distribution is similar. The bioavailability of oral furosemide in infants appeared to be low. The findings of this study indicate that furosemide, 1 mg/kg parenterally, given with a frequency of more than twice daily to the premature infant in the immediate neonatal period, or in parenteral dosages in excess of 2 mg/kg, may lead to plasma levels associated with ototoxicity.

Biological Availability↗

PubMed2002

Furosemide modulation of GABA(A) receptors in dopaminergic neurones of the rat substantia nigra.

Furosemide is a diuretic which has been shown to decrease recombinant GABA(A) receptor (GABA(A)R)-mediated currents and also to block epileptiform discharges. Here, we show that furosemide actions on GABA(A)Rs of rat substantia nigra dopaminergic neurones depend on both furosemide and GABA(A)R agonist concentrations. The whole-cell currents induced by low concentrations of GABA (5 microM) or by the selective GABA(A)R agonist isoguvacine (7-25 microM) were enhanced by 200 microM furosemide. However, furosemide did not affect GABA(A)R currents induced by 60 microM isoguvacine and even decreased those induced by 200 microM isoguvacine. At the single-channel level, furosemide had comparable effects. It increased the open time proportion with 7 microM isoguvacine but had no significant effect on the open time proportion with 60 microM isoguvacine. These effects resulted from a differential action on the multiple conductance levels activated by GABA(A)R agonists. The concentration-response relationship to isoguvacine in the whole-cell mode revealed the presence of a high and a low apparent affinity GABA(A)R population (EC(50) 4.8 vs 89 microM). These two populations of receptors coexist in the same dopaminergic neurone. They are both furosemide-sensitive and may represent different GABA(A)R subunit assemblies.

Animals↗

PubMed1996

Blunted furosemide action on cerebellar GABAA receptors in ANT rats selectively bred for high alcohol sensitivity.

Furosemide specifically reverses the inhibition by gamma-aminobutyric acid (GABA) of t-[35S]-butylbicyclophosphorothionate ([35S]TBPS) binding and increases the basal [35S]TBPS binding to the cerebellar granule cell layer GABAA receptors. For the selectivity of furosemide, an interplay between GABAA receptor alpha 6 and beta 2 or beta 3 subunits is needed. We have now investigated the furosemide sensitivity of cerebellar [35S]TBPS binding in the alcohol-sensitive (ANT) rat line that harbors a pharmacologically critical point mutation in the alpha 6 subunit [alpha 6 (Q1000)], increasing benzodiazepine affinity of the normally insensitive alpha 6-containing receptors. ANT receptors were less efficiently affected by furosemide, while a normal GABAA receptor antagonism was observed with a specific GABAA receptor antagonist SR 95531. Reduced [3H]muscimol binding in ANT samples and small alterations in situ hybridization signals for alpha 1, alpha 6, beta 2, beta 3, gamma 2 and delta subunit mRNAs failed to correlate with impaired cerebellar furosemide efficacy in individual animals. The alpha 6 (q100) ANT mutation was not responsible for the reduced efficacy of furosemide in the ANT rat line, as judged from the potent furosemide antagonism in recombinant ANT-type alpha 6 (Q100)beta 3 gamma 2 receptors. This data suggest that presence of a novel abnormality in the structure and/or expression of alpha 6 subunit-containing GABAA receptors in the ANT rat line.

Animals↗

PubMed1999

A pharmacoeconomic assessment of torsemide and furosemide in the treatment of patients with congestive heart failure.

The management of patients with congestive heart failure (CHF) can place a significant economic burden on managed care organizations, leading providers to seek treatments that are cost-effective. Diuretics play a significant role in the treatment of edema associated with CHF. We evaluated the use of 2 loop diuretics, torsemide and furosemide, in patients with CHF in a managed care setting. This prospective study compared clinical, economic, and quality-of-life outcomes in 240 patients randomized to the 2 drugs. Patients with New York Heart Association (NYHA) class II or class III CHF requiring loop diuretic treatment, either alone or in conjunction with other therapy, were eligible. Patients were told about the study during an office visit, and those with an interest in participating and who met the eligibility criteria were given further information and the opportunity to participate. After investigators obtained informed consent, patients were enrolled, randomized to either treatment, and followed for 6 months. Outcomes included CHF/cardiovascular (CV)-related medical costs, change in NYHA class, change in sodium retention score, hospitalizations, physician visits, medication use, adverse events, and change in quality of life. A total of 103 patients were randomized to torsemide, and 137 patients were randomized to furosemide. Except for body weight, patient demographic characteristics did not differ between groups at baseline; patients in the torsemide group were significantly heavier (P = 0.004). The results showed that mean total CHF/CV-related medical costs did not differ between groups (torsemide, $1520.07; furosemide, $1503.26; P = 0.975), despite higher mean drug-acquisition costs for torsemide patients ($121.01 vs $42.95; P < 0.0001). Mean costs were similar for CHF/CV-related hospitalizations (torsemide, $845.84; furosemide, $893.33; P = 0.918) and CHF-related physician visits (torsemide, $138.80; furosemide, $164.09; P = 0.288). Quality of life was significantly better for patients in the torsemide group at month 4 (P = 0.017), but not at month 2 (P = 0.059) or month 6 (P = 0.269). The number of adverse events did not differ significantly between groups (torsemide, 221; furosemide, 287; P = 0.916). The results of this study appear to indicate that in a representative cross-section of managed care patients, those who received torsemide, despite higher drug-acquisition costs, had similar CHF/CV-related management costs compared with furosemide recipients.

Aged↗

PubMed1996

Pharmacokinetics and pharmacodynamics of torasemide and furosemide in patients with diuretic resistant ascites.

BACKGROUND/AIM: To evaluate the pharmacokinetics and pharmacodynamics of furosemide and torasemide in patients with cirrhosis and diuretic resistant ascites. METHODS: Eighteen patients were randomly allocated to receive intravenous torasemide (40 mg) or furosemide (80 mg). The renal response to these drugs was assessed in baseline conditions and in the 24 h following drug administration together with plasma and urinary concentrations of furosemide, torasemide and its metabolites. RESULTS: Torasemide induced significantly greater diuretic and natriuretic effects than furosemide in the first hour after drug administration. No other significant differences between the two drugs were observed with respect to the renal response to these drugs. Torasemide reached a lower maximum plasma concentration than furosemide, but the former drug had a longer apparent terminal half-life and lower renal and non-renal clearances. Comparing these results with those previously reported in healthy subjects, both drugs showed a reduced elimination rate through renal and non-renal routes, and a larger distribution to body fluids. As a consequence, the half-life of both drugs was longer than in healthy subjects. Urinary excretion of pharmacologically active species, however, was quantitatively unchanged after torasemide administration, whereas it was reduced after furosemide. Finally, the natriuretic potency of both drugs was markedly reduced in these patients. CONCLUSIONS: The pharmacokinetics and pharmacodynamics of torasemide and furosemide are markedly altered in patients with diuretic resistant ascites.

Adult↗

PubMed1999

Long-term furosemide treatment in the normal rat: dissociation of glomerular hypertrophy and glomerulosclerosis.

Furosemide treatment produces glomerular hypertrophy and augments glomerular capillary hydraulic pressure in the normal rat. Similar processes have been implicated in the progression of glomerulosclerosis (GS). Whereas prior experiments with furosemide treatment of 6 to 8 weeks duration have produced no detrimental effects on renal function or structure, the effects of more prolonged treatment are unknown. Male Munich-Wistar rats were pair fed with or without furosemide, 40 mg/d, from the time of weaning through 10 months of age. At selected time points, 24-hour urine collections were obtained for total protein and volume determination. At the end of the study, light and electron microscopic morphometric studies were performed. Renal cortical hypertrophy and glomerular hypertrophy were sustained throughout the 9 months of treatment in the group receiving furosemide. The cortical interstitial area was increased in the furosemide group, but this did not appear to be the result of fibrosis. Proximal and distal tubule diameter were unaffected by treatment. No differences in GS or glomerular ultrastructure were shown. This study provides no evidence of detrimental glomerular effects of furosemide in normal animals. Further studies of furosemide treatment under conditions of preexisting renal pathological conditions are warranted to confirm the safety of this treatment in situations analogous to those seen in the clinical setting. Interstitial expansion also warrants further study in this setting.

Animals↗

PubMed1999

The effect of combined administration of cadmium and furosemide on auditory function in the rat.

A number of heavy metals have been associated with toxic effects to the peripheral or central auditory system. These include lead, arsenic, mercury, platinum and organic tin compounds. In addition, the ototoxic effects of some metals may be potentiated by other factors. However, the auditory effects of cadmium have not previously been reported. The purpose of the present study was to investigate the potential ototoxic effects of cadmium from an acute dosage, and its potentiation by furosemide. Auditory brainstem response (ABR) thresholds were measured in adult Sprague-Dawley rats. Rats received either cadmium chloride (5 mg/kg, i.p.) followed by saline (4 ml/kg, i.p.). cadmium chloride followed by furosemide (200 mg/kg, i.p.), or furosemide alone. Follow-up ABRs were carried out 7 days post-treatment and threshold changes were compared between each treatment group. No significant threshold change was seen for the cadmium chloride plus saline treated or the furosemide treated animals. However, significant threshold elevations were observed in animals receiving cadmium chloride plus furosemide. In addition, scanning electron microscopy revealed extensive hair cell loss in animals treated with cadmium chloride and furosemide. Although functional auditory changes were not seen after the administration of cadmium alone, the potentiation of threshold changes by furosemide suggests that cadmium may be ototoxic under certain conditions.

Animals↗

PubMed1987

Influence of tablet dissolution on furosemide bioavailability: a bioequivalence study.

In order to evaluate the in vitro dissolution and in vivo bioavailability relationship for furosemide, a bioequivalence study was carried out. Furosemide (40 mg) was administered orally to 12 normal volunteers in a 6 x 6 crossover design using six products (five tablets and one solution) obtained from three pharmaceutical companies. Plasma and urine concentrations of furosemide were quantitated by high-performance liquid chromatography (HPLC). Plasma furosemide profiles were analyzed by non-compartmental methods. Compared to the oral solution, all of the formulations exhibited lower peak furosemide concentrations, longer mean residence times, and, in some cases, diminished bioavailability (range, 66-96%). Similar results were obtained when the reference product (a rapidly dissolving tablet) was used as the standard. All of the products failed the 75/75 rule when compared to either reference standard, apparently because of large intersubject variability. The total amount of furosemide excreted in urine could be associated with the percentage drug dissolved (in vitro) at 30 min. The pH 5.6 dissolution medium (compared to pH 4.6) appears to be an appropriate test medium for assuring batch uniformity and bioequivalence of furosemide products.

Administration, Oral↗

PubMed2002

[Long-term diuretic treatment in heart failure: are there differences between furosemide and torasemide?].

BACKGROUND: Treatment for congestive heart failure (CHF) is an important factor in rising health care costs especially in patients requiring repeated hospitalisations. Diuretics remain the most frequently utilized drugs in symptomatic patients. In this study the long-term outcome under furosemide and torasemide, two loop diuretics with different pharmacokinetic properties, were evaluated during one year in an ambulatory care setting. AIMS: Comparison of hospitalization rates and estimated costs under long-term treatment with furosemide and torasemide in patients with CHF. METHODS: Retrospective analysis of disease course and resource utilization in 222 ambulatory patients receiving long-term treatment with furosemide (n = 111) or torasemide (n = 111). Data were also compared to those of a similar study including 1000 patients in Germany. RESULTS: Patients receiving long-term treatment with torasemide had a lower hospitalisation rate (3.6%) compared to patients on furosemide (5.4%). Corresponding hospitalization rates in the German study were 1.4% under torasemide and 2% under furosemide. The higher hospitalisation rates in Swiss patients could be explained by a higher average age (75 years vs. 69 years) and a longer duration of symptomatic heart failure (4.1 yrs vs. 0.7 yrs). Cost estimates based on the average number of hospital days (0.54 under torasemide compared to 1.05 under furosemide) indicated that the financial burden could be halved by a long-term torasemide treatment. CONCLUSION: Torasemide with its more complete and less variable bioavailability offers potential clinical and economic advantages over furosemide in the long-term treatment in patients with CHF.

Adult↗

PubMed1980

Renal tubular secretion and effects of furosemide.

Continuous intravenous infusion of furosemide (8 mg/hr) to 6 healthy subjects induced an average diuresis at steady state of 667 +/- 144 ml/30 min (+/- SD) with a mean plasma concentration of furosemide of 623 +/- 209 ng/ml. The urinary output of Cl- was 50.4 +/- 7.5, of Na+ 47.7 +/- 8.7, and of K+ 5.4 +/- 0.6 mmole/30 min. Intravenous injection of probenecid (1 gm) raised the plasma furosemide level to a maximum of 1,584 +/- 151 ng/ml. Despite this, the urinary excretion of water, Cl-, Na+, and K+ decreased to 52%, 39%, 39%, and 52%, respectively, of control values. Probenecid greatly reduced the urinary excretion and renal clearance of furosemide. There was no or negative correlation between the plasma levels of furosemide and its diuretic and saluretic effects. The urinary excretion and renal clearance of the diuretic correlated positively with these effects. No effect of probenecid on protein binding of furosemide was detected. The findings show that the diuretic effects of furosemide depend on active tubular secretion of the drug and thus on its tubular fluid concentration.

Adult↗

PubMed1982

Canrenoate reversal of inhibitory effects of digoxin on basal and furosemide-stimulated renin secretion.

Changes in plasma renin activity (PRA) were monitored in six mildly hypertensive men after intravenous doses, in seven separate experiments, of placebo, digoxin, potassium canrenoate, potassium canrenoate with digoxin, furosemide, furosemide with digoxin, and potassium canrenoate with furosemide and digoxin. Potassium canrenoate has been used as a rapid source of canrenone, which has been recently shown to be a competitive antagonist of ouabain at its Na-K-ATPase receptor site. Potassium canrenoate infusion reversed the hyporeninemic effect of digoxin. This result has been taken as evidence that: (1) antialdosteronic drugs can also reverse digoxin effects at extracardiac level and (2) the Na-K-ATPase system is involved in the renin secretory mechanism. A seemingly identical reversal of the hyporeninemic effect of digoxin was induced by furosemide, which, when given alone, stimulated renin secretion. The simultaneous administration of potassium canrenoate, digoxin, and furosemide induced an increase in PRA on the same order as that after furosemide alone. This result indicates that furosemide stimulates renin release by affecting a biochemical system other than that affected by digoxin.

Adult↗

PubMed1982

Hemodynamic effects of nitroprusside and furosemide in left ventricular failure.

Nitroprusside and furosemide are both used to treat acute left ventricular failure, but their hemodynamic effects have not been compared in the same patients. In 13 patients with acutely decompensated chronic left ventricular failure, we infused nitroprusside to reduce pulmonary wedge pressure to normal without inducing hypotension. When hemodynamics returned to control after stopping nitroprusside, furosemide was given ase a 200-mg rapid infusion. Control hemodynamic values before each drug were in the same range. Mean arterial pressure fell from 99.9 +/- 16.7(SD) to 74.8 +/- 10.5 mm Hg on nitroprusside (P less than 0.001) and was unchanged after furosemide. Nitroprusside reduced pulmonary wedge pressure from 30.5 +/- 6.9 to 15.9 to 6.0 mm Hg (P less than 0.001), while furosemide reduced it to 27.5 +/- 8.5 mm Hg (P less than 0.05). Cardiac index rose from 2.33 +/- 0.78 l/min/m2 to 3.62 +/- 0.93 l/min/m2 (P less than 0.001) on nitroprusside and remained unchanged at 2.32 +/- 0.64 l/min/m2 after furosemide. At the same pulmonary wedge pressure on each drug (24 mg Hg), cardiac index was increased by nitroprusside (+0.6 +/- 0.5 l/min/m2, P less than 0.01) and unchanged by furosemide. Thus, furosemide reduces only preload without changing cardiac output in patients with left heart failure, whereas nitroprusside at similar or lower preload in the same patients reduces afterload and raises cardiac output and improves left ventricular performance. Nitroprusside appears preferable for the immediate treatment of left ventricular failure.

Aged↗

PubMed1987

Mechanism of furosemide resistance in analbuminemic rats and hypoalbuminemic patients.

To elucidate the mechanism of resistance of hypoalbuminemic patients to furosemide, the effect of this diuretic on urine volume of normal and analbuminemic rats (NAR) and of hypoalbuminemic patients was studied. Intravenous administration of furosemide rapidly enhanced sodium diuresis in normal rats but not in NAR. Total plasma clearance and distribution volume of furosemide were much larger in NAR than in normal rats, while no significant difference in these pharmacokinetic parameters was observed for the unbound fraction of the diuretic between the two animal groups. In contrast, urinary secretion of furosemide was significantly lower in NAR than in normal rats. Injected furosemide bound to albumin markedly promoted diuresis in NAR, while the same dose of albumin alone had no effect, indicating that binding to albumin is essential for the delivery of furosemide to the kidney, the site for its action. Injection of the complex rapidly increased the urine volume of hypoalbuminemic patients who showed a marked resistance to this diuretic. Thus, the resistance to furosemide in both NAR and hypoalbuminemic patients may be explained on the same basis.

Animals↗

PubMed2006

The connecting tubule is the main site of the furosemide-induced urinary acidification by the vacuolar H+-ATPase.

Final urinary acidification is achieved by electrogenic vacuolar H(+)-ATPases expressed in acid-secretory intercalated cells (ICs) in the connecting tubule (CNT) and the cortical (CCD) and initial medullary collecting duct (MCD), respectively. Electrogenic Na(+) reabsorption via epithelial Na(+) channels (ENaCs) in the apical membrane of the segment-specific CNT and collecting duct cells may promote H(+)-ATPases-mediated proton secretion by creating a more lumen-negative voltage. The exact localization where this supposed functional interaction takes place is unknown. We used several mouse models performing renal clearance experiments and assessed the furosemide-induced urinary acidification. Increasing Na(+) delivery to the CNT and CCD by blocking Na(+) reabsorption in the thick ascending limb with furosemide enhanced urinary acidification and net acid excretion. This effect of furosemide was abolished with amiloride or benzamil blocking ENaC action. In mice deficient for the IC-specific B1 subunit of the vacuolar H(+)-ATPase, furosemide led to only a small urinary acidification. In contrast, in mice with a kidney-specific inactivation of the alpha subunit of ENaC in the CCD and MCD, but not in the CNT, furosemide alone and in combination with hydrochlorothiazide induced normal urinary acidification. These results suggest that the B1 vacuolar H(+)-ATPase subunit is necessary for the furosemide-induced acute urinary acidification. Loss of ENaC channels in the CCD and MCD does not affect this acidification. Thus, functional expression of ENaC channels in the CNT is sufficient for furosemide-stimulated urinary acidification and identifies the CNT as a major segment in electrogenic urinary acidification.

Acid-Base Equilibrium↗