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PubMed2004

Increasing the dose of furosemide in patients with azotemia and suspected obstruction.

Diuresis renography is widely used to distinguish obstructed from nonobstructed kidneys; however, the delivery of furosemide to its site of action in the loop of Henle is impaired in patients with azotemia. Consequently, the standard adult dose of 40 mg furosemide could be insufficient to generate an adequate diuretic response. This problem is illustrated by a patient with azotemia with bilateral nephrostomies who underwent Tc-99m MAG3 (mercaptoacetyltriglycine) diuresis renography with 40 mg furosemide to determine if his bilateral ureteral obstruction had resolved. The study showed findings typical for obstruction despite the fact that the patient could not have been obstructed because the nephrostomy tubes had not been clamped. When the study was repeated 6 days later with 80 mg furosemide and clamped nephrostomy tubes, there was good drainage bilaterally excluding obstruction. The nephrostomy tubes were removed and the patient's creatinine has subsequently remained stable for 3 years. In summary, this report illustrates the rationale for increasing the dose of furosemide in patients with azotemia referred for diuresis renography and shows how increasing the dose of furosemide could improve the diuretic response and minimize false-positive or indeterminate results.

Aged↗
PubMed1987

Na+, K+ and water balance in young spontaneously hypertensive rats: relationship to blood pressure after high K+ treatment.

These studies were designed to investigate the effects of high dietary K+ on electrolyte and water balance in young spontaneously hypertensive rats (SHR) and to relate these effects to changes in blood pressure. The high K+ diet reduced blood pressure by approximately 10 mmHg during the development of hypertension. Blood pressure, however, plateaued at the same maximum level as control by age 13 weeks. Rats fed the high K+ diet showed a significant increase in water intake and urine volume throughout the treatment period but no change in plasma volume or extracellular fluid volume occurred. A slight natriuresis was also observed in rats on the high K+ diet, but this was not of sufficient magnitude to decrease total body Na+. These results confirm previous findings that K+ causes a diuresis and a natriuresis, but demonstrate that the diuretic action of K+ cannot explain its antihypertensive properties in young SHR.

Animals↗
PubMed1997

Anti-diuresis in the blood-feeding insect Rhodnius prolixus Stål: the peptide CAP2b and cyclic GMP inhibit Malpighian tubule fluid secretion.

Rhodnius prolixus eliminates NaCl-rich urine at high rates following its infrequent but massive blood meals. This diuresis involves stimulation of Malpighian tubule fluid secretion by diuretic hormones released in response to distention of the abdomen during feeding. The precipitous decline in urine flow that occurs several hours after feeding has been thought until now to result from a decline in diuretic hormone release. We suggest here that insect cardioacceleratory peptide 2b (CAP2b) and cyclic GMP are part of a novel mechanism of anti-diuresis. Secretion rates of 5-hydroxytryptamine-stimulated Malpighian tubules are reduced by low doses of CAP2b or cyclic GMP. Maximal secretion rates are restored by exposing tubules to 1 mmol l-1 cyclic AMP. Levels of cyclic GMP in isolated tubules increase in response to CAP2b, consistent with a role for cyclic GMP as an intracellular second messenger. Levels of cyclic GMP in tubules also increase as urine output rates decline in vivo, suggesting a physiological role for this nucleotide in the termination of diuresis.

Animals↗
PubMed1986

Piretanide, a potent diuretic with potassium-sparing properties, for the treatment of congestive heart failure.

The diuretic and clinical efficacy and safety of piretanide, a new high-ceiling loop diuretic, was determined in patients with mild to moderately severe congestive heart failure. Piretanide (n = 20) administered orally in a daily dosage of up to 24 mg was compared with placebo (n = 18) for 28 days, using a double-blind, randomized, parallel design. Patients were hospitalized during the first 5 days of the study when dosage titration was established and 24-hour fractionated urine collections were obtained. Piretanide caused significant diuresis for 3 hours after ingestion with a natriuretic response noted for up to 6 hours. While occasional kaliuretic response was noted, it did not significantly increase 24-hour urinary potassium excretion. Only one patient treated with the highest allowed dose of piretanide developed mild hypokalemia. An improvement in New York Heart Association functional class status was noted after piretanide therapy. In contrast, patients who received placebo exhibited no significant improvement. BUN increased in nine piretanide-treated patients; two were discontinued from the study because of progressive azotemia. However, there was no significant increase in serum creatinine levels. Other blood, physical, ECG, and audiometric examinations also revealed no significant abnormalities. The study suggests that oral piretanide is a relatively safe and effective diuretic for treating congestive heart failure with a potential advantage of having potassium-sparing properties.

Adult↗
PubMed2006

Indomethacin differentiates the renal effects of sphingosine-1-phosphate and sphingosylphosphorylcholine.

The sphingomyelin breakdown products sphingosine-1-phosphate (S1P) and sphingosylphosphorylcholine (SPC) constrict intrarenal microvessels in vitro in a pertussis toxin (PTX) sensitive manner, and S1P also reduces renal blood flow in vivo. Nevertheless, both S1P and SPC have been reported to enhance diuresis and natriuresis. This pattern is similar to that of neuropeptide Y, which also reduces renal blood flow and enhances diuresis and natriuresis. The latter effects are inhibited by the cyclooxygenase inhibitor indomethacin, and various S1P and SPC responses have also been linked to the cyclooxygenase pathway. Therefore, we have investigated whether indomethacin can alter the renal effects of S1P and SPC in anaesthetised rats in vivo. In line with earlier experiments S1P bolus injections dose-dependently reduced renal blood flow (by up to 4.8 +/- 0.5 ml min(-1)), and this was not significantly affected by indomethacin treatment (5 mg kg(-1) i.p.). Infusion of S1P but not of SPC (30 microg kg(-1) min(-1) each) for 60 min reduced renal blood flow by up to 0.8 +/- 0.2 ml min(-1), and this was not markedly altered by indomethacin. Despite the differential renovascular effect, both S1P and SPC enhanced diuresis by up to 215 +/- 65 and 201 +/- 58 microl 15 min(-1) respectively, and natriuresis by up to 25 +/- 9 and 29 +/- 11 micromol 15 min(-1) respectively. While indomethacin abolished the SPC-induced diuresis and natriuresis, it, if anything, slightly enhanced the diuretic and natriuretic effect of S1P. To determine whether tubular SPC effects are receptor-mediated, PTX experiments were performed. SPC-induced enhancements of diuresis and natriuresis were abolished by PTX. We conclude that S1P, SPC and neuropeptide Y exhibit distinct patterns of modulation of renal function and that indomethacin allows such effects to be differentiated.

Animals↗
PubMed1990

Traditional management of liver disorders.

Dietary measures have achieved mixed results in the management of liver disorders. Although a high energy diet may shorten the course of viral hepatitis by a relatively small amount, dietary restriction is usually of no benefit in compensated cirrhosis. Restriction of sodium intake to 22 to 60 mol/day leads to resolution of cirrhotic ascites in approximately 20% of patients, and reduces the requirement for diuretics in the remainder. In advanced liver disease, diet plays an important role in the avoidance of portal-systemic encephalopathy (PSE), with the tolerance of most nutrients, most importantly protein, being sharply reduced. Despite the frequent presence of carbohydrate intolerance in liver disease, carbohydrate supplementation may be required to ensure adequate utilisation of the reduced dietary protein intake. Zinc supplementation may also be required in liver cirrhosis to compensate for a deficiency. Bed rest is an important component of the management of acute and chronic liver disorders, together with the avoidance of fatigue. Abstinence from alcohol is required in alcoholic liver disease patients, who should receive parenteral thiamine 100 mg and other vitamin and mineral supplementation as required. Agents acting on the ascending loop of Henle [such as furosemide (frusemide)] or the distal tubule (such as spironolactone) are the diuretics most frequently employed to mobilise ascites in cirrhosis, the latter drug being the more effective in nonazotaemic patients. In the absence of oedema, the diuresis should be restricted to a maximum of 750 ml/day; however, patients with oedema may safely undergo a diuresis of less than or equal to 1.5 L/day. Diuretic therapy is often associated with renal complications, such as azotaemia (usually reversible) and severe hyponatraemia in cirrhotic patients with ascites; spironolactone may produce antiandrogenic adverse effects. Lactulose, used in the treatment of acute and chronic PSE, acts by inhibiting gastrointestinal absorption of ammonia and other toxic nitrogenous substances, and by reducing urea degradation. Other pharmacological treatments, such as branched-chain amino acids and benzodiazepine antagonists have a limited role in the management of PSE. Chronic cholestasis has been treated with cholestyramine and fat-soluble vitamins, whereas ursodeoxycholic acid appears to be a promising agent in the treatment of primary biliary cirrhosis. In chronic hepatitis, the prevention of development of cirrhosis is a primary treatment goal which has been attempted with variable success using antifibrotic drugs such as penicillamine and colchicine.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Cortex Hormones↗
PubMed1980

[Furosemide and metolazone: a highly effective diuretic combination].

The natriuretic and diuretic effects of combined treatment with furosemide and metolazone have been studied quantitatively. 15 hospitalized patients with severe fluid retention who showed no reduction of body weight despite treatment with furosemide received metolazone in addition for 3 days. 11 patients had biventricular heart failure with edema, and 4 had cirrhosis of the liver with ascites. Following the addition of metolazone at a starting dose of 2.5 mg/d, a highly significant increase in diuresis and natriuresis, with a corresponding reduction in body weight, was seen in all patients pretreated with a daily dose of 40-370 mg furosemide (mean 122 mg/d). On the first day of this combined treatment the mean sodium excretion increased from 131 to 303 mval/d (2 p less than 0.01) and the mean urine volume increased from 1677 to 2940 ml/d (2 p less than 0.01). The mean reduction in body weight was 6.1 kg (2 p less than 0.001) within 7 days of continuous treatment. Even at low doses metolazone significantly potentiates the diuretic effects of furosemide and therefore simplifies the treatment of fluid retention. High doses of furosemide can be avoided in many cases, a factor of particular advantage in ambulatory long term therapy and in patients with decreased kidney function. It may also lower the cost of the therapy. In 3 patients the furosemide dose had to be lowered after metolazone was started, to avoid an excessive negative fluid balance. These cases clearly demonstrate the importance of daily checks on the patient's body weight after starting combined therapy with furosemide and metolazone.

Ascites↗
PubMed2001

Effects of L-arginine and furosemide on blood pressure and renal function in volume-expanded rats.

1. The aim of the present study was to investigate the effects of L-arginine (L-Arg) on blood pressure and water and electrolyte excretion in control and extracellular fluid volume-expanded rats (10% bodyweight with 0.9% NaCl) and to determine whether diuretic treatment with furosemide (FUR) can be optimized by the administration of L-Arg in this model. 2. Both groups of animals were anaesthetized, divided into groups and treated with either 7.5 mg/kg FUR, 250 mg/kg L-Arg, 1 mg/kg NG-nitro-L-arginine methyl ester (L-NAME), FUR + L-NAME or FUR + L-Arg. Mean arterial pressure (MAP), diuresis, natriuresis and kaliuresis were determined. 3. Extracellular fluid volume expansion induced no changes in MAP in control and volume-expanded rats (92+/-6 vs 100+/-8 mmHg, respectively). The hypotension induced by FUR in control and volume-expanded rats (69+/-7 and 76+/-5 mmHg, respectively) was significantly (P < 0.01) enhanced by the administration of L-Arg (54+/-3 and 64+/-3 mmHg, respectively). 4. Injection of L-NAME increased MAP and diminished diuresis, natriuresis and kaliuresis in both groups. 5. Furosemide-induced water and electrolyte excretion was blunted by the administration of L-NAME. 6. The combination of L-Arg + FUR increased diuresis induced by FUR alone (control rats: 29.33+/-1.68 vs 12.91+/- 0.41 microL/min per 100 g, respectively; volume-expanded rats: 248.5+/-25.4 vs 112,6+/-8.3 microL/min per 100 g, respectively; P < 0.01). 7. The administration of the combination of L-Arg + FUR promoted a decrease in the sodium/water excretion ratio compared with the administration of FUR alone (control rats: 0.230+/-0.018 vs 0.45+/-0.03, respectively, P < 0.001; volume-expanded rats: 0.091+/-0.010 vs 0.22+/-0.03, respectively, P < 0.01). 8. The potassium/water excretion rate induced by FUR alone and in the presence of L-Arg followed a pattern similar to that seen for natriuresis (control rats: 0.35+/-0.05 vs 0.20+/-0.05 microEq/min per 100 g, respectively; volume-expanded rats: 0.045+/-0.008 vs 0.014+/-0.003 microEq/min per 100 g, respectively; P < 0.01). 9. The decrease in the electrolyte/water excretion ratio observed with FUR + L-Arg in volume-expanded rats was greater than in control animals. 10. The results of the present study show that the administration of FUR with L-Arg contributes to enhanced hypotensive and diuretic effects of FUR, thus diminishing the relative electrolyte excretion in normal conditions and in extracellular fluid volume expansion.

Animals↗
PubMed2003

Prevention and nondialytic treatment of acute renal failure.

Based on the progress made during the last few years in understanding the pathophysiology of acute renal failure, a plethora of therapeutic drug and nondrug interventions have been developed and tested in animal and human forms of this disease. The first part of this article focuses on the role of volume expansion and vasopressors in the prevention and treatment of acute renal failure in the critically ill. From all prophylactic measures that have been proposed, volume expansion, or at least correction of volume depletion, remains the most efficient and most evidence-based intervention in these patients. Norepinephrine is, out of all the vasopressors, probably the most appropriate to use in cases of hypotension, provided circulating volume is adequate. In hypotensive septic patients, vasopressin has been shown to be useful. Direct renal vasodilating substances, the most popular still being low-dose dopamine, have never been proved to be useful in carefully performed prospective trials. Moreover dopamine especially is associated with a number of side effects and complications. From the agents acting on tubular factors, the diuretic mannitol and loop diuretics are the most prescribed. Only in specific situations such as rhabdomyolysis and kidney transplant surgery has it been shown that mannitol was able to prevent acute renal failure. The loop diuretics are able, after establishing adequate circulating volume, to promote diuresis in some forms of oliguric acute renal failure; however, some recent papers have shown that the administration of loop diuretics may actually be associated with increased mortality and delayed recovery of renal function. The last few years have seen a number of trials with acetylcysteine in the prevention of mainly radiocontrast nephropathy. Although the results are still conflicting, the majority indicates that acetylcysteine, when applied together with adequate volume expansion, may be a useful drug to incorporate in the standard treatment procedures in patients at risk for acute renal failure. Interventions to stimulate the recovery process of the damaged kidney with growth factors, although theoretically sound, have thus far not led to successful results.

Acetylcysteine↗
PubMed1979

[Renal kallikrein-kinin system and control of blood pressure (author's transl)].

Kallikrein excreted with the urine appears to be formed in the kidney. The kallikrein-kinin system in the kidney is localized in the distal nephron from the juxtaglomerular apparatus to the collecting duct. It has been shown that intrarenal infusion of kinins produces an increase in renal blood flow as well as diuresis and natriuresis. Part of the effect of kinins appears to be mediated by the release of prostaglandins. However, the precise role of the renal kallikrein-kinin system in sodium and volume homeostasis and in blood pressure regulation still remains to be determined. Mineralocorticoids as well as the diuretics furosemide, bumetanide and bendroflumethiazide increase, spironolactone decreases kallikrein excretion. Urinary kallikrein has been shown to increase acid-as well as cryoactivation of prorenin in vitro. It is unclear as yet, however, whether the renal kallikrein-kinin system takes part in converting inactive prorenin into active renin in vivo. There are reports on subnormal, normal as well as increased kallikrein excretion in spontaneously hypertensive rats. In rats susceptible to the hypertensive effect of salt a substantially decreased excretion of kallikrein has been observed. Kallikrein excretion has been described to be increased in primary aldosteronism and to be reduced in a proportion of patients with established essential hypertension. In patients with labile hypertension, however, kallikrein excretion appears to be normal suggesting that decreased urinary kallikrein in essential hypertension is a consequence rather than a cause of hypertension. The renal kallikrein-kinin system does not appear to play a primary role in the pathogenesis of hypertension.

Angiotensin II↗
PubMed1979

Effect of diuresis on urokinase excretion rate.

UK excretion rate in the diuretic state was investigated in human and animal studies. Loading of water, beer or diuretics in man decreased the UK excretion rate as urine flow increased. A linear relation between UK excretion rate and urine specific gravity was observed. Simultaneous loading of water and exercise suppressed the decrease in UK excretion rate and the increase in urine flow. In animal studies, a null value for UK excretion rate was observed as a result of giving physiological saline and/or furosemide, and a remarkable increase in urine flow was induced. These results clearly suggest the existence of a relation between renal function and UK excretion rate.

Animals↗
PubMed1999

A pilot study on the hemodynamic effect of short-term ursodeoxycholic acid therapy in patients with stable liver cirrhosis.

OBJECTIVE: Total serum bile acid concentrations are elevated in individuals with liver disease. Ursodeoxycholic acid (UDCA) therapy in such patients results in a further significant rise in plasma levels to the extent that it becomes the major circulating bile acid. In laboratory animals, bile acids, such as taurocholic acid, have also been shown to possess a diuretic-like action, as they can promote diuresis, natriuresis, and kaliuresis by inhibiting tubular sodium reabsorption. The aim of the present study was to assess the effect of 1 month's UDCA therapy on cardiovascular function in cirrhotic patients. METHODS: Two groups of patients with cirrhosis were studied, six with primary biliary cirrhosis (PBC) and six with postnecrotic liver cirrhosis (PNC). Cardiovascular function was assessed by determination of blood pressure, heart rate, and by two-dimensional and pulsed Doppler echocardiography. RESULTS: In PBC patients, 1 month's treatment with UDCA significantly reduced diastolic volume without changing systolic, diastolic, and mean blood pressures, heart rate, systolic and stroke volumes, ejection fraction, cardiac output, and systemic vascular resistance. In PNC patients, UDCA significantly reduced cardiac output, with a tendency to reduce left ventricular volumes, without any changes in systolic, diastolic, and mean blood pressures. CONCLUSIONS: UDCA caused reductions in diastolic volume in the PBC patients and cardiac output in the PNC patients. Such reductions are not unlike that seen in individuals treated with diuretics. This diuretic-like action deserves further study, particularly in cirrhotic patients who are also being treated with diuretics or show evidence of cardiac myopathy.

Adult↗
PubMed1991

Effects of nifedipine on renal responses to several diuretic agents in rats.

The influence of the dihydropyridine calcium antagonist nifedipine has been studied on the diuretic response to frusemide, acetazolamide and hydrochlorothiazide in water-loaded (25 mL kg-1) conscious rats. Oral administration of nifedipine (10 mg kg-1) markedly inhibited frusemide- and hydrochlorothiazide-induced diuresis as evidenced by a reduction in 5 h urine volume and urinary sodium and potassium elimination. However, it neither significantly enhanced nor limited urine and electrolyte excretion promoted by acetazolamide. Nifedipine, 5 and 10 mg kg-1 but not 1 mg kg-1, significantly (P less than 0.05) inhibited the diuretic response of hydrochlorothiazide. At doses which affect hydrochlorothiazide diuresis (5 and 10 mg kg-1), nifedipine was found to depress the mean arterial pressure by 32% in normotensive rats. These results are of interest in view of the often reported clinical side effect of nifedipine in promoting peripheral oedema in hypertensive patients and its use in combination with a thiazide or loop diuretic.

Animals↗
PubMed1986

Human atrial natriuretic peptide (ANP) for the treatment of patients with liver cirrhosis and ascites.

The acute effects of human atrial natriuretic peptide (ANP) were investigated in 10 patients with liver cirrhosis and ascites. In all patients, diuresis and natriuresis were stimulated with a wide individual variation (50 to 500%) in response to a bolus injection of 30 micrograms ANP. No side effects of treatment were observed. Continuous infusion of ANP (300 micrograms/10 h/d) in a patient with liver cirrhosis and ascites, resistant to conservative forms of diuretic therapy, resulted in an initial increase of diuresis and natriuresis which subsequently returned to pretreatment levels. After initiation of pulsatile nocturnal treatment (5 pulses of 30 micrograms ANP every 3 h), diuresis increased, leading to a persistent normalization of sodium and chloride excretion. The patient lost 8 kg of weight during 16 days of treatment. Out of 3 additional patients on the same therapeutic regime, only one experienced a weight loss of 5 kg due to increased natriuresis and chloruresis. The remaining 2 patients did not respond during 5 resp. 7 days of therapy.

Adult↗
PubMed1989

Interference of different ACE-inhibitors with the diuretic action of furosemide and hydrochlorothiazide.

In healthy volunteers the acute effect of furosemide (40 mg i.v.) and hydrochlorothiazide (100 mg p.o.) on diuresis, natriuresis and renal kallikrein and kinin excretion was investigated. Furosemide stimulated markedly diuresis and natriuresis as well as urinary kallikrein and kinin excretion. Pretreatment by captopril (C) reduced the diuretic and natriuretic effect of furosemide significantly probably due to a diminished (about 50%) proximal-tubular secretion of furosemide. Captopril did not alter significantly the furosemide induced changes in urinary kallikrein and kinin excretion. After captopril there was a clear dissociation between aldosterone, which was diminished by captopril continuously, and renal kallikrein and kinins, which were still stimulated by furosemide. These results suggest that renal kallikrein-kinin system is stimulated by furosemide directly and independently of aldosterone secretion. Other ACE-inhibitors like ramipril (5 mg) or enalapril (20 mg) did not influence the stimulatory effects of furosemide on diuresis or kallikrein-kinin excretion. Ramipril at a dose of 10 mg, however, enhanced the initial diuretic effect of furosemide by increased furosemide secretion and increased relative sodium excretion. Hydrochlorothiazide induced a prolonged diuresis which was not changed by either captopril or ramipril. Urinary kallikrein excretion was not stimulated by hydrochlorothiazide. Our results show an important drug interference between captopril and furosemide, which is independent of ACE-inhibition and probably only due to an interference in proximal-tubular secretion of both drugs. Between captopril and hydrochlorothiazide no such interaction could be observed.

Adult↗
PubMed1987

Plasma atrial natriuretic peptide and spontaneous diuresis in sick neonates.

Plasma concentrations of immunoreactive human atrial natriuretic peptide (human ANP) were sequentially determined in 12 infants with respiratory distress syndrome (RDS) or meconium aspiration syndrome (MAS) during various phases of diuresis to elucidate the role of human ANP in the occurrence of spontaneous diuresis in the newborn. Plasma immunoreactive ANP concentrations during the diuretic as well as the maximum diuretic phase were significantly (p less than 0.001) higher than during the prediuretic phase. A gradual decrease occurred during the post diuretic phase, returning to prediuretic values after one week of life. Significant natriuresis, increased glomerular filtration rate, mild hyponatremia, and decreased blood pressure were observed in the diuretic phase in all the cases studied. These results suggest that hypersecretion of human ANP may play an important part in initiating spontaneous diuresis in sick neonates.

Atrial Natriuretic Factor↗
PubMed2004

The effect of drinking tea at high altitude on hydration status and mood.

The effect of drinking tea on hydration status and mood was studied in nine male and four female members of expeditions based at Mt. Everest base camp at an altitude of 5,345 m. Whilst exposed to altitude-cold diuresis, participants were subjected to a crossover experimental design comprising two 24-h dietary interventions. In the "tea" condition, hot brewed tea formed a major part of fluid intake, whereas in the "no-tea" condition tea was excluded from the diet. Subjects were prohibited in both cases from consuming other caffeinated beverages, caffeinated foods, and alcoholic drinks. Mean fluids ingested [mean (SE); tea=3,193 (259) ml versus no tea=3,108 (269) ml] and urine volume (tea=2,686 (276) ml versus no tea=2,625 (342) ml] were similar under both conditions. Statistical analysis found no difference in urine stimulated as a result of the tea intervention (P=0.81). Several markers of hydration status were also taken immediately pre and post each condition, including measures of urine specific gravity, urine electrolyte balance (K+, Na+), and urine colour. None of these measures indicated a difference in hydration status as a result of the dietary intervention in either the control or tea condition. A difference was, however, found in mood, with subjects reporting reduced fatigue when tea was included in the diet (P=0.005). The study shows therefore that even when drunk at high altitude where fluid balance is stressed, there is no evidence that tea acts as a diuretic when consumed through natural routes of ingestion by regular tea drinkers, but that it does have a positive effect on mood.

Adaptation, Physiological↗
PubMed2006

Indomethacin decreases furosemide-induced natriuresis and diuresis on the neonatal kidney.

Indomethacin is used to pharmacologically occlude patent ductus arteriosus in preterm infants. It induces renal untoward effects and furosemide is administered simultaneously to counteract them. The effect of furosemide is blunted by indomethacin. We analyzed comparatively the interactions of furosemide and indomethacin at the organic anion transport system in adult and newborn individuals. Adult and 5-day-old Wistar rats were allocated into three groups: (1) indomethacin (10 mg/kg, ip); (2) furosemide (2 mg/kg, ip); and (3) indomethacin/furosemide, at the same doses. Urinary flow, glomerular filtration rate (GFR), sodium and potassium fractional excretions, and free-water and osmolal clearances were estimated. Para-aminohippuric acid (PAH) uptake was measured in renal cortical slices to study the organic anion's secretory pathway. In adult and newborn rats, furosemide-induced increments in urinary fluxes and excretions of sodium and potassium were blunted by indomethacin administered simultaneously. PAH uptake was decreased to a further extent by indomethacin than by furosemide, suggesting that inhibition of the diuretic effect might be related to competition in the secretion of furosemide. Inhibitory interaction between indomethacin and furosemide was achieved at approximately 10-fold lower concentrations in the newborn than in the adult rats, suggesting that tubular secretion in the neonate is more sensitive to the action of these drugs than in the adult individual.

Animals↗