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PubMed1988

Diuretic-induced urinary flow rates at varying clearances and their relevance to the performance and interpretation of diuresis renography.

Minute-by-minute urinary flow rates before and after the intravenous injection of 40 mg frusemide were investigated in 29 well hydrated adult patients with varying creatinine clearances. Total urinary flow rates 3 to 6 min after frusemide ranged from 1 to 42 ml/min (mean 19). At 15 to 18 min after the diuretic, flow rates ranged from 8 to 46 ml/min (mean 23). Flow rates were proportional to creatinine clearance (r = 0.73; r = 0.8) and decreased with falling clearance, although significant diuresis (4 ml/min/kidney) was achieved down to single kidney clearances of 10 ml/min. Where single kidney clearances were less than 31 ml/min, single kidney flow rates of 10 ml/min or more were not guaranteed. Below this clearance, diuresis renography remains completely reliable and unequivocal in the majority of cases. However, perfusion pressure flow studies will not necessarily be urodynamically comparable and it should not be expected that the results of the two tests will agree in individual cases of upper tract dilatation. Recommended timing for frusemide administration should be 20 min into the test, or 15 min before radiopharmaceutical injection.

Aged↗
PubMed2003

Agonist/antagonist properties of nalbuphine, butorphanol and (-)-pentazocine in male vs. female rats.

To determine whether sex differences in the effects of mixed-action opioids could be due to differential activity at mu or kappa receptors, agonist/antagonist properties of nalbuphine, butorphanol and (-)-pentazocine were compared in male vs. female rats using a diuresis test. In water-loaded rats (2-h test), nalbuphine and (-)-pentazocine dose-dependently increased urination similarly in both sexes, whereas butorphanol increased urination more in females than in males on a ml/kg basis. The diuretic effects of all three opioids were at least partially blocked by the kappa receptor-selective antagonist nor-binaltorphimine (nor-BNI, 5 mg/kg) in both sexes. Kappa receptor-mediated antagonism of diuresis induced by U69,593 (0.56 mg/kg) was only observed with butorphanol in males. In water-loaded rats (1-h test), nalbuphine did not suppress, and butorphanol and (-)-pentazocine significantly suppressed urination in males only; all three mixed-action opioids dose-dependently blocked the antidiuretic effect of the selective mu agonist fentanyl (0.056 mg/kg) in both sexes. The ability of nalbuphine and (-)-pentazocine to block fentanyl-induced antidiuresis was not affected by pretreatment with nor-BNI in either sex. In contrast, the ability of butorphanol to block fentanyl-induced antidiuresis was attenuated by pretreatment with nor-BNI in males but not in females. These results suggest that sex differences in the effects of these mixed-action opioids are primarily due to their greater relative efficacy at the mu receptor in male than in female rats; butorphanol also may have greater efficacy at kappa receptors in females than in males.

Animals↗
PubMed1983

Cis-diamminedichloroplatinum (DDP) induced acute renal failure (ARF): attempts at amelioration.

Nephrotoxicity is a dose limiting feature of cis-diamminedichloroplatinum (DDP) cancer chemotherapy. We have previously developed a model of DDP induced acute renal failure in the rat, which is characterized by non oliguric progressive azotemia. Protocols have been established in humans to prevent or diminish DDP associated renal alterations during the course of cancer chemotherapy. The present studies were designed to evaluate the effect of prior diuretic therapy, with furosemide, and enhanced solute diuresis, using dextrose and water as the sole source of drinking fluid, on DDP induced acute renal failure in the rat. As compared to water drinking controls neither the diuretic nor the enhancement of osmotic excretion effected DDP associated mortality. The courses of the acute renal failure observed in all three study groups were similar; however, there was a suggestion in the surviving animals that these maneuvers may have contributed to a more rapid return in renal function among rats not dying of DDP induced acute renal failure.

Acute Kidney Injury↗
PubMedDate not supplied

[Diuretic and hypotensive effects of Nigella sativa in the spontaneously hypertensive rat].

Nigella sativa (ranunculaceae) is used in Arab folk medicine as a diuretic and hypotensive plant. We report here the diuretic and hypotensive effects of dichloromethane extract of Nigella sativa seeds in the spontaneously hypertensive rat (SHR). An oral dose of Nigella sativa extract (0.6 ml/kg/day) and furosemide (5 mg/kg/day) increased significantly the diuresis by 16 and 30 per cent respectively after 15 days of treatment; urinary excretion of Cl-, Na+, K+ and urea is also increased. Simultaneously, the mean arterial pressure decreased respectively by 22 and 18 per cent in the Nigella sativa treated rat and nifédipine treated rat (0.5 mg/kg/day). In conclusion, the diuretic activity observed in the SHR rat treated with Nigella sativa seeds may be partially responsible for its diuretic action; it seems that other pathways may also be involved in their cardiovascular effects.

Animals↗
PubMed1976

The effects of bumetanide on renal function and blood composition in sheep.

Respones to bumetanide were studied in five ewes. During ADH infusion urine flow increased from less than 1-0 to approximately 11-5 cm3 min-1 within 30 min of intravenous injection of 0-02 mg kg-1 bumetanide and returned to approximately 2-0 cm3 min-1 within 3 h of dosing. The diuresis was accompanied by large increases in sodium and chloride excretion and smaller increases in potassium and free hydrogen ion excretion. Bicarbonate excretion and TCH20 were reduced. Plasma potassium and chloride concentrations decreased slightly while arterial bicarbonate pH and pCO2 slightly increased. A transient increase in GFR and RPF was followed by a small reduction in GFR. No change in CH20 was observed after bumetanide injection during water diuresis. Increasing the dose of bumetanide over the range 0-002 to 0-20 mg kg-1 resulted in more pronounced and prolonged responses. The results show that bumetanide is a potent diuretic in sheep with its main site of action on the ascending limb of Henle's loop.

Animals↗
PubMed1990

Diuretic effect and diuretic efficiency after intravenous dosage of frusemide.

1. Frusemide was given intravenously at a dose of 5 mg kg-1 to five healthy volunteers and the diuresis was assessed by frequent spontaneous voiding over 5 h. Urinary volume and contents of sodium, chloride, potassium and frusemide were measured. 2. Diuretic response was evaluated using the sigmoid Emax model and non linear regression of diuresis vs frusemide excretion rate. The time courses of diuresis (pharmacological effect) and diuretic efficiency were constructed from the fitted parameters of the sigmoid Emax model. 3. The frusemide excretion rate associated with maximum efficiency was found, as predicted theoretically, to be less than the excretion rate associated with 50% of maximum effect in four of the five subjects in whom the slope factor was less than 2. 4. The effect over time is dependent both on the instantaneous drug effect but also on its pharmacokinetic properties and mode of administration. An intravenous bolus is the least efficient mode of administration while a controlled input producing a frusemide excretion at maximum efficiency should yield up to a 2.3 times higher diuretic response.

Adult↗
PubMed1990

Indomethacin affects the development of tolerance to ethanol-induced diuresis.

The present study analyzes the effect of indomethacin on the development of tolerance to the diuretic effect of ethanol. Male Wistar rats were treated with ethanol (2 g kg-1 day-1, ip) over a period of 4 weeks and the effect of ethanol on diuresis was assessed weekly. A significant tolerance to the diuretic effect of ethanol was detected after 3 weeks of treatment. However, rats treated simultaneously with ethanol plus indomethacin (5 mg/kg, ip, on alternate days) showed no tolerance to ethanol even after 4 weeks of treatment. The fact that indomethacin prevented the development of tolerance to the diuretic effect of ethanol but had no influence on diuresis per se suggests that prostaglandins play a significant role in the mechanisms of tolerance to ethanol.

Animals↗
PubMed1993

Plasma atrial natriuretic factor during cold-induced diuresis.

The purpose of this study was to evaluate the possible contribution of atrial natriuretic factor (ANF) to cold-induced diuresis. Seven healthy men, dressed in shorts, were exposed to a cold environment (+12 degrees C) for 90 min, and also to a thermoneutral environment. Exposure to cold increased urine output and sodium excretion significantly but plasma ANF concentration remained unchanged. The increase in urinary potassium excretion during cold exposure was not significant (P = 0.0636) and plasma renin activity did not change either. Exposure to cold increased mean arterial pressure significantly but it did not affect heart rate. We concluded that acute exposure to the cold environment induced a diuretic response, which was a solute diuresis in its nature. Our results did not give support to the hypothesis that ANF might be involved in the renal response to cold exposure.

Adolescent↗
PubMed1986

Pharmacokinetics and diuretic effect of bumetanide following intravenous and intramuscular administration to horses.

Concentrations of the potent diuretic bumetanide were determined by a sensitive high performance liquid chromatographic procedure in plasma and urine from horses following intravenous and intramuscular administration of a dose rate of 15 micrograms/kg. The elimination half-life was found to be 6.3 min, the volume of distribution at steady state 68 ml/kg and the total plasma clearance 10.9 ml/min/kg. The onset of diuresis occurred within 15 min and diuresis was no longer apparent 1 h after i.v. administration. Given by the intramuscular (i.m.) route, bumetanide was rapidly absorbed; bioavailability was 70-80%. i.m. administration of bumetanide prolonged its plasma half-life (11-27 min) and enhanced and prolonged its diuretic effect.

Animals↗
PubMed2005

Increased basal phosphorylation of detrusor smooth muscle myosin in alloxan-induced diabetic rabbit is mediated by upregulation of Rho-kinase beta and CPI-17.

Urinary bladder dysfunction caused by the alteration of detrusor smooth muscle (DSM) is one of the complications of diabetes. It is well established that smooth muscle contractility is regulated by an elevation of cytosolic Ca(2+) via myosin light chain (MLC) phosphorylation. However, recent studies have shown the modulation of MLC phosphorylation without a rise in Ca(2+) in smooth muscle and that two key molecules (Rho-kinase and CPI-17) are involved in the regulation of calcium sensitization. This study investigates the effect of diabetes on DSM calcium sensitization. Diabetes was induced by alloxan in New Zealand White rabbits, and age-matched rabbits given 5% sucrose in the drinking water served as control for diuresis. Two-dimensional gel electrophoresis showed that basal MLC phosphorylation level was significantly higher in diabetic animals than normal or diuretic controls, and Rho-kinase-specific inhibitor, Y-27632, decreased MLC phosphorylation level. Adding Y-27632 to bethanechol-precontracted DSM strips can induce muscle relaxation, but it occurred much more slowly in diabetic samples compared with controls. RT-PCR, Western blot analysis, and immunohistochemistry revealed the overexpression of Rho-kinase beta and CPI-17 at both mRNA and protein levels in response to diabetes. In conclusion, our results demonstrate that Rho-kinase contributes to DSM MLC phosphorylation and there is a higher basal MLC phosphorylation level in diabetic DSM. Our results also suggest that this high basal MLC phosphorylation may be due to the upregulation of Rho-kinase and CPI-17. Thus Rho-kinase- and CPI-17-mediated Ca(2+) sensitization might play a role in diabetes-induced alteration of the detrusor contractility and bladder dysfunction.

Amides↗
PubMed2006

Initial experience with fenoldopam after cardiac surgery in neonates with an insufficient response to conventional diuretics.

OBJECTIVE: Fenoldopam, a selective dopamine-1 receptor agonist, causes systemic vasodilation and increased renal blood flow and tubular sodium excretion. We hypothesized that urine output would improve when fenoldopam was added to conventional diuretic therapy after neonatal cardiopulmonary bypass. DESIGN: Retrospective cohort study using a time-series design. SETTING: Pediatric cardiac intensive care unit. PATIENTS: All neonates who received fenoldopam to promote diuresis after cardiac surgery requiring cardiopulmonary bypass from February 2002 through December 2004. INTERVENTIONS: Fenoldopam infusion for inadequate urine output despite conventional diuretics. MEASUREMENTS: Demographics, diagnostic information, and surgical procedures were recorded. Urine output, fluid balance, inotrope scores, diuretic doses, and other clinical variables that may influence diuresis were recorded for the 24-hr period immediately preceding fenoldopam initiation and during the initial 24 hrs of drug administration. MAIN RESULTS: A total of 25 neonates received fenoldopam to promote diuresis after the modified Norwood (n = 14), arterial switch (n = 4), or other operations (n = 7). Heart rate, conventional diuretic dosing, and fluid intake were similar during the 24-hr periods of conventional therapy and fenoldopam use (p = not significant for all), whereas inotrope scores decreased during the study (p = .021). There was a small but statistically significant increase in blood pressure during the 48-hr study period. Median urine output was 3.6 mL x kg(-1) x hr(-1) (range, 0.2-7.2 mL x kg(-1) x hr(-1)) during the 24-hr period of conventional therapy and 5.8 mL x kg(-1) x hr(-1) (range, 1.6-11.7 mL x kg(-1) x hr(-1)) during the initial 24 hrs of fenoldopam administration (Wilcoxon's signed-rank test, p = .001). CONCLUSIONS: Fenoldopam may improve urine output in neonates who are failing to achieve an adequate negative fluid balance despite conventional diuretic therapy after cardiac surgery and cardiopulmonary bypass. This study is limited by its retrospective design and the possibility that urine output improved spontaneously during the treatment period. A randomized, placebo-controlled clinical trial will be required to confirm these findings.

Cardiopulmonary Bypass↗
PubMed1998

Treatment of heartwater: potential adverse effects of furosemide administration on certain homeostatic parameters in normal sheep.

Diuretics, in particular furosemide, are generally recommended as a supportive treatment in the advanced stages of heartwater in ruminants. However, after what appeared to be possible adverse effects accompanying its use in field cases of heartwater, the effects of this drug on certain blood and urine parameters were investigated in normal sheep at the same dose rates. Diuresis with concomitant natriuresis was significant after furosemide administration, as was the expected plasma volume decrease. Other significant changes included metabolic alkalosis, hypokalaemia and reduced blood ionised calcium. The difference in duration of the diuretic effect and the duration of the changes in blood parameters from c. 3 h and c. 6 h respectively make it difficult to determine a time interval between successive treatments with furosemide. It appears that the probable cause of death of sheep with heartwater is a drastic reduction in blood volume and decreased cardiac output that leads to general circulatory failure. A therapeutic approach that involves further loss of plasma volume due to diuresis appears contradictory. The added effects of potentiating respiratory alkalosis and the terminal drop in blood ionised calcium seen in heartwater-affected animals indicate that the use of furosemide in supportive treatment of this disease is not warranted.

Alkalosis↗
PubMed1994

Diuretic effect of clonidine during isoflurane, nitrous oxide, and oxygen anesthesia.

BACKGROUND: Because clonidine, a relative selective alpha 2-agonist, inhibits the action of arginine vasopressin (AVP), the authors examined whether clonidine as an oral preanesthetic medication would induce diuresis and also would affect AVP release and its action during general anesthesia. METHODS: Fifty-seven patients (aged 18-65 yr) randomly received oral clonidine either approximately 5 micrograms.kg-1 (n = 19), approximately 2.5 micrograms.kg-1 (n = 19), or none (n = 19) in addition to oral famotidine 20 mg, 90 min before arrival at operating room. Urine volume, urine osmolality, and amount of sodium and potassium excreted into urine were examined every hour for 3 h during minor surgery under general anesthesia with isoflurane and nitrous oxide in oxygen. For 5 patients of each group, plasma AVP and atrial natriuretic peptide concentrations and urine cyclic adenosine monophosphate concentrations as an index of AVP action were also assayed. RESULTS: Urine output indices (calculated as hourly urine output [milliliters per hour] divided by body weight [kilograms]) were significantly greater in the all periods (P < or = 0.035) after the initiation of anesthesia in the patients receiving clonidine 5 micrograms.kg-1 and only in the 3rd h in those receiving clonidine 2.5 micrograms.kg-1 (P = 0.047) as compared with those in the patients given famotidine alone. The peak effects of diuresis and natriuresis induced by oral clonidine 5 micrograms.kg-1 were both observed at the 2nd h (mean +/- SEM, 2.4 +/- 0.4 ml.kg-1.h-1 and 5.7 +/- 1.5 mEq.h-1 vs. 0.6 +/- 0.1 ml.kg-1.h-1 and 2.2 +/- 0.5 mEq.h-1 in the control subjects; P = 0.001 and P = 0.049). Kaliuresis also increased in the patients receiving clonidine 5 micrograms.kg-1 in the 2nd and 3rd h (P < or = 0.003). Urine osmolality showed a significant reduction over time in patients given clonidine but not in the control subjects. However, plasma AVP and atrial natriuretic peptide levels, and urine cyclic adenosine monophosphate concentrations did not significantly differ among the three groups. CONCLUSIONS: Oral preanesthetic medication of clonidine 2.5 or 5 micrograms.kg-1 caused a significant diuretic effect during surgery under general anesthesia, though it did not apparently relate to AVP action. This effect of clonidine could be related to its pharmacological action as an alpha 2-adrenoceptor agonist not necessarily restricted to the kidney. The diuretic effect of clonidine implicates its clinical importance in the management of patients during anesthesia.

Administration, Oral↗
PubMed1992

The influence of posture on the response to loop diuretics in patients with chronic cardiac failure is reduced by angiotensin converting enzyme inhibition.

The diuretic and natriuretic response to an intravenous dose of frusemide 40 mg was assessed in the erect and supine positions in 10 patients with cardiac failure who were being treated with enalapril 10 mg twice daily in addition to diuretics (Enalapril group) and in 10 patients with cardiac failure taking diuretics alone (Control group). Total 4 h diuresis in the erect position was 728 ml and in the supine position was 824 ml in the patients taking enalapril compared to 655 ml in the erect position and 1166 ml in the supine position in those patients taking diuretics alone. Total 4 h natriuresis in the erect positions was 78 mmol and in the supine position was 85 mmol in patients taking enalapril 10 mg twice daily but in those patients taking diuretics alone total 4 h natriuresis in the erect position was 67 mmol increasing to 120 mmol in the supine position. Measurements of plasma renin activity and plasma angiotensin II concentration confirmed effective converting enzyme inhibition, in the group of patients taking enalapril, but in those patients taking diuretics alone the erect position was associated with an increase in plasma renin activity, and plasma concentrations of angiotensin II and aldosterone. We conclude that the renin angiotensin system is a major factor in mediating the effect of posture on loop diuretic drugs.

Adult↗
PubMed2005

Sodium magnetic resonance imaging of diuresis: spatial and kinetic response.

Renal function is highly correlated with the sodium concentration gradient along the corticomedullary axis. The application of 3D high-resolution sodium magnetic resonance imaging (MRI) provided a means to quantify in vivo the spatial and temporal changes in renal tissue sodium concentration under normal and diuretic conditions. A detailed, pixel-by-pixel analysis of the intact rat kidney sodium MR images yielded a quantitative measure of the corticomedullary sodium gradient before and at early and later times after the administration of two distinct diuretic agents, furosemide and mannitol. Furosemide, a loop diuretic, induced a fivefold reduction in the cortical-outer medullary sodium gradient, whereas mannitol, an osmotic diuretic, did not affect this gradient. Both diuretics induced a 50% decrease in the sodium concentration of the inner medulla; however, mannitol exerted its effect twice as fast as furosemide with a 2.5-min exponential decay constant. These specific changes were attributed to the different mechanism of action and site of activity of each diuretic agent. Thus, high-resolution (23)Na MRI offers a unique, noninvasive tool for functional imaging of the kidney physiology.

Analysis of Variance↗
PubMed1977

[Diuresis and natriuresis following application of bemeticide and triamterence in rats on normal and low-potassium diet (author's transl)].

The investigations were carried out under identical conditions and were aimed at determining the effects of different doses of the two diuretics: 3-(alpha-methylbenzyl)-6-chloro-7-sulfamyl-3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxide (bemeticide) and 2,4,7-triamino-6-phenylpteredine (triamterene) as well as for their joint administration at ratios of 1:2 and 1:4, resp., with regard to renal elimination of sodium and potassium as well as to urinary output in normally and low-potassium-fed rats. The 1:2 combination of bemeticide and triamterene resulted in an optimum diuretic and sodium elimination effect with potassium values within normal range, both in the normally and in the low-potassium-fed animals. An increase of the triamterene component from the 1:2 to the 1:4 ratio did not yield additional advantages.

Animals↗
PubMed1995

Acute changes in urinary excretion of nitrite + nitrate do not necessarily predict renal vascular NO production.

NO2 + NO3 (NOx), the stable oxidation products of NO, and cGMP are widely accepted as indices of in vivo NO production. Whether acute changes in urinary excretion of nitrite + nitrate (UNOXV) can be taken to reflect acute changes in renal and/or systemic NO production is not known. The present studies were conducted in the conscious rat to investigate the effect on acute changes in UNOxV, of maneuvers that (a) enhance NO production and (b) act as diuretics. L-arginine (L-arg) and acetylcholine (Ach) produce equivalent NO dependent falls in renal vascular resistance (RVR), but a much greater increase in UNOX V is seen with L-arg. D-arg does not stimulate NO and has no renal vasodilatory effect, but produces a large rise in UNOX V, and SNP lowers BP but not RVR and results in a reduced UNOX V. None of the diuretics employed should stimulate the NO system or lower RVR; however, the proximally acting agents, acetazolamide and D-arg increased UNOx V, while the loop diuretic furosemide had little effect. H2O diuresis (a distal event) led to a fall in UNOx V. These data suggest that NOx is reabsorbed extensively in the proximal tubule and that inhibition of proximal reabsorption leads to an increase in UNOx V. Also, our results show that the relationship between UNOx V and UcGMP V is unpredictable. Therefore, we conclude that measurements of acute changes in UNOxV and/or UcGMP V should be interpreted cautiously, since they may reflect altered tubular handling of NOx rather than the acute activity of the systemic and/or renal NO systems.

Acetylcholine↗