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PubMed1976

Patient tolerance of long-term diuretic/potassium supplement therapy.

Forty patients with congestive heart failure or hypertensive heart disease were given long-term maintenance treatment with a combined bumetanide/slow-release potassium supplement preparation ('Burinex K'). Stabilised doses ranged from 0.5 mg to 2 mg bumetanide with from 7.7 mmol to 30.8 mmol potassium. Patients took doses either at 9 a.m. or at 5 p.m. daily during a series of alternate 2 to 4-weekly treatment periods. Analysis of patient preference for morning or evening diuresis showed that the majority (72.5%), including all 18 patients who went out to work, preferred the evening regimen. Bumetanide proved to be a highly effective diuretic, irrespective of time of administration. Evening diuresis was associated with a statistically significant increase in the 24-hour excretion of sodium. Serial laboratory analyses showed no clinically significant changes in serum potassium or other parameters examined an in contrast to other diuretics bumetanide produced no significant hyperuricaemic effects.

Adult↗

PubMed1992

Pharmacological properties of the novel highly potent diuretic 7-chloro-2,3-dihydro-1-(2-methylbenzoyl)-4(1H)-quinolinone 4-oxime-O-sulfonic acid potassium salt.

7-Chloro-2,3-dihydro-1-(2-methylbenzoyl)-4(1H)-quinolinone 4-oxime-O-sulfonic acid potassium salt (M17055, CAS 114417-20-8) showed potent diuretic and saluretic effects dose-dependently, in rats (p.o.), mice (p.o.) and dogs (i.v.), at doses of 0.1-100 mg/kg, 0.3-100 mg/kg and 0.01-30 mg/kg, respectively. The efficacy of M17055 for diuresis, natriuresis and chloruresis was much higher than that of hydrochlorothiazide and almost the same as that of furosemide. These results indicate that this compound may be classified as a "high ceiling diuretic". The potencies of M17055 for natriuresis in rats (p.o.), mice (p.o.) and dogs (i.v.) calculated with ED50 values were 38, 34 and 24 times, respectively, more potent than those of furosemide. Urinary excretions of sodium, chloride and potassium increased in parallel with urinary volume with the administration of M17055 or furosemide, whereas an apparent dissociation with urinary calcium and sodium excretion was observed with M17055 alone. In rats, the increase of urinary calcium excretion with M17055 was significantly lower than that with furosemide under comparable conditions of natriuresis. Moreover, in mice, M17055 decreased urinary calcium excretion at doses with low effectiveness. In clearance studies using anesthetized dogs, M17055 suppressed negative free water clearance (CH2O) under saline loaded conditions, and it decreased positive CH2O under water diuretic conditions. These changes in the effects on CH2O induced by M17055 resemble those of loop diuretics. However, M17055 could not shift negative CH2O to positive, while furosemide was able to do so. Moreover, positive CH2O decreased to nearly zero with M17055, while urine remained dilute with furosemide even at 30 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1988

Effects of furosemide therapy on free-water excretion in uremic patients.

To assess the intrinsic effects of treatment with furosemide on free-water excretion in patients with chronic renal failure, two groups of patients with and without replacement of diuretic-induced salt losses have been studied. Furosemide therapy was administered for 1 week during constant sodium intake (100 mEq/day). In neither of the groups did furosemide cause hyponatremia, while it did decrease the urine to plasma osmolality ratio, an effect lasting even when the diuretic effect was exhausted. During water diuresis, furosemide decreased the fractional sodium reabsorption in diluting segments but not the absolute rate of the free-water generation (CH2O). Presumably the expected decrease of CH2O was masked by the increased distal delivery of tubular fluid mainly due to an additional effect of the diuretic on the proximal tubule. The hypotonicity of urine after furosemide treatment may be secondary to the dissipation of medullary hypertonicity, caused by furosemide, in the condition of decreased water permeability of the collecting duct due to uremic disease.

Furosemide↗

PubMed2002

Resistive index: an experimental study of the effects of diuretic stimulation in the unobstructed porcine kidney.

OBJECTIVE: To study the effects of diuretic stimulation with frusemide and mannitol on the renal resistive index (RI) of the undilated unobstructed porcine kidney. MATERIALS AND METHODS: Experiments were carried out on 14 pigs divided into two equal groups (A and B), under general anaesthesia. In all pigs both ureters were catheterized, thereby allowing urine output to be measured on each side separately, and an indwelling catheter in a femoral artery used to continuously measure the systemic blood pressure. Furthermore, in five pigs from each group, right renal blood flow was measured by ultrasonic flow probes placed around the renal arteries. The right kidney RI was measured at baseline and at 5-min intervals after frusemide (group A) and mannitol (group B) stimulation, for 75 min. RESULTS: Frusemide caused significant increases in diuresis (P < 0.001) and renal blood flow (P = 0.009). This was accompanied by a significant decrease in mean arterial pressure (P < 0.001). The RI was unaffected (P = 0.706), with mean values in group A of 0.58-0.65. Mannitol also caused a significant increase in diuresis (P < 0.001) and a subtle but significant decrease in mean arterial pressure (P < 0.001). However, renal blood flow was unaffected by the diuretic (P = 0.820); the mean RI values were unaffected, at 0.61-0.66 (P = 0.375). CONCLUSIONS: These results show that diuretic stimulation with frusemide or mannitol does not affect the RI of the unobstructed undilated porcine kidney, despite significant changes in diuresis, renal blood flow and mean arterial pressure.

Animals↗

PubMed2001

Influence of diuretics on the concentration of proteins and other components of pleural transudates in patients with heart failure.

PURPOSE: Diuretic therapy increases the total protein and lactate dehydrogenase concentrations in pleural fluid in patients with transudates due to heart failure, but the effect of diuresis on other substances in pleural fluid constituents is not known. SUBJECTS AND METHODS: Twenty-one patients with transudative pleural effusions due to congestive heart failure were prospectively studied. Repeated diagnostic thoracentesis (mean +/- SD = 3 +/- 1; range, 2 to 6) was performed until the effusions were radiographically unapparent (5 +/- 2 days). Thirty-one patients with congestive heart failure who underwent only a single thoracentesis after diuretic therapy served as controls. We measured the concentrations of various components of pleural effusions in the serum and in the pleural fluid, and determined the serum-pleural fluid gradient (serum concentration minus pleural fluid concentration) and ratio (serum concentration divided by pleural fluid concentration). RESULTS: The pleural concentrations of most components increased significantly (P <0.001) from the initial specimen to the final specimen: total protein, from 23 +/- 7 g/L to 33 +/- 9 g/L; albumin, from 13 +/- 4 g/L to 18 +/- 6 g/L; lactate dehydrogenase, from 177 +/- 62 U/L to 288 +/- 90 U/L; cholesterol, from 31 +/- 16 mg/dL to 52 +/- 22 mg/dL; and cholinesterase, from 1,304 +/- 616 U/L to 1,884 +/- 674 U/L. Expressed as percentage change, the increases in the serum-pleural fluid gradients for albumin (12% +/- 22%) and total protein (11% +/- 12%) were significantly less than the increases in their concentrations in pleural fluid (albumin, 47% +/- 49%; total protein, 48% +/- 40%) or in their pleural fluid/serum ratios (albumin, 27% +/- 29%; total protein, 38% +/- 34%). CONCLUSIONS: The concentrations of the biochemical components commonly measured in pleural fluid increase progressively during diuretic therapy. Calculation of the serum-pleural fluid gradients for protein and albumin may be the most useful way to distinguish transudates from exudates in patients with congestive heart failure who have undergone diuresis.

Aged↗

PubMed1979

[Renal blood flow, diuresis and isotope nephrogram in experimental stenosis of the renal artery (author's transl)].

After experimental stenosis of the renal artery of the dog, the isotope nephrogram shows a prolongation of the transit-time, when the renal blood flow is reduced to 40--70%. This finding was most significant in low diuresis (0,05--0,2 ml/min), sporadic in moderate diuresis (0,2--2,0 ml/min), no longer demonstrable in forced diuresis (greater than 2,0 ml/min). The diuretic effect of X-ray contrast medium (70% Na-Meglumin-Jotalamat, 0,5 ml/kg i.v.) normalizes a pathologic ING in low diuresis.

Animals↗

PubMed1987

A new diuretic that does not reduce renal handling of uric acid in rats, S-8666.

The uric acid-retaining effects of diuretics were studied using sodium-restricted spontaneously hypertensive rats. Test agents were administered orally once a day for two weeks. Diuretic thiazides such as trichlormethiazide and hydrochlorothiazide and loop diuretics such as furosemide and indacrinone clearly reduced the renal function for uric acid excretion in treatment which produced major effects such as diuresis, saluresis and hypotension. However, a new diuretic with uricosuric activity, S-8666, developed in our laboratories, had no effect on the renal handling of uric acid at doses which showed major effects similar to those of other diuretics. The results should aid the understanding of the utility of S-8666 as a new diuretic antihypertensive which does not cause hyperuricemia during therapy.

Animals↗

PubMed1998

Long-term regulation of inner medullary collecting duct urea transport in rat.

Facilitated urea transport is regulated acutely by arginine vasopressin (AVP) and hyperosmolality in rat terminal inner medullary collecting duct (IMCD). This study tested whether chronic diuresis or antidiuresis regulates facilitated urea transport. Basal and AVP-stimulated urea permeabilities (Purea) were measured in perfused IMCD subsegments. Rats were made: (1) diuretic by giving them sugar water (with or without food) or furosemide; or (2) antidiuretic by water deprivation. They were then compared with untreated rats given food and water ad libitum. Terminal IMCD from untreated rats had a high basal Purea that was significantly increased by AVP. Diuresis significantly increased basal Purea in terminal IMCD in all five diuresis protocols. Water deprivation for 1 or 3 d had no effect on basal or AVP-stimulated Purea in the IMCD2 subsegment of the terminal IMCD. In contrast, 3 d of water deprivation significantly increased both basal and AVP-stimulated Purea in the IMCD3 subsegment; 1 d of water deprivation had no effect on basal or AVP-stimulated Purea. Next, initial IMCD (IMCD1) were studied. Initial IMCD from untreated rats had a low basal Purea that was not increased by AVP (10 nM). Water diuresis (with or without food) for 3 to 5 d had no effect on basal Purea but significantly increased AVP-stimulated Purea. Furosemide diuresis and water diuresis for 1 or 7 d had no effect on either basal or AVP-stimulated Purea in initial IMCD. Water deprivation for 2 to 3 d, but not for 1 d, significantly increased basal Purea in initial IMCD, whereas water deprivation for 1 d increased AVP-stimulated Purea. It is concluded that chronic changes in hydration cause heterogeneous changes in facilitated urea transport in rat IMCD subsegments.

Animal Feed↗

PubMed1996

Noninvasive evaluation of intrarenal oxygenation with BOLD MRI.

BACKGROUND: The countercurrent arrangement of capillary blood flow in the medulla of mammalian kidneys generates a gradient of oxygen tension between the renal cortex and the papillary tip that results in a state of relative hypoxia within the renal medulla. Exploration of the pathophysiological implications of medullary hypoxia has been hampered by the absence of a noninvasive technique to estimate intrarenal oxygenation in different zones of the kidney. In the present study, we demonstrate the feasibility of such a method on the basis of blood oxygenation level-dependent (BOLD) MRI, which allows sequential measurements in humans in response to a variety of physiological/ pharmacological stimuli in health and disease. METHODS AND RESULTS: BOLD MRI measurements were obtained in healthy young human subjects (n = 7), and the effects of three different pharmacological/physiological maneuvers that induce diuresis were studied. Spin-spin relaxation rate, R2*, was measured, which is directly related to the amount of deoxyhemoglobin in blood and in turn to tissue PO2. Furosemide but not acetazolamide (n = 6 each) increased medullary oxygenation (delta R2* = 7.62 Hz; P < .01), consistent with the separate sites of action of these diuretics in the nephron and with previous direct measurements of their effects in anesthetized rats with oxygen microelectrodes. A new finding is that water diuresis improves medullary oxygenation (delta R2* = 6.43 Hz; P < .01) in young human subjects (n = 5). CONCLUSIONS: BOLD MRI can be used to monitor changes in intrarenal oxygenation in humans in a noninvasive fashion.

Acetazolamide↗

PubMed2004

Diuretic activity of Spilanthes acmella flowers in rats.

In the Sri Lankan traditional medicine, Spilanthes acmella Murr. (Family: Compositae) flowers are claimed to possess powerful diuretic activity. However, as yet, the diuretic potential of these flowers is not investigated by scientifically controlled studies. The aim of this study was to evaluate the diuretic potential of Spilanthes acmellaflowers in rats using a cold-water extract (CWE). Different concentrations of CWE (500, 1000, 1500 mg/kg) or vehicle or furosemide (13 mg/kg) were orally administered (N = 6 per each treatment group) to hydrated rats and their urine output was monitored at several intervals of time (1-5 h). The highest dose of CWE significantly (P < 0.05) and markedly increased the urine output. The onset of this diuretic action was extremely prompt (within 1 h) and lasted throughout the studied period (up to 5 h). The peak effect was evident between 1 and 2 h. Further, the intensity of diuresis induced by the CWE in the first hour was almost similar to that of furosemide. Spilanthes acmella CWE also caused marked increase in urinary Na(+) and K(+) levels and a reduction in the osmolarity of urine suggesting that it is mainly acting as a loop diuretic. It may also inhibit ADH release and/or action. It is concluded that the Spilanthes acmella CWE has strong diuretic action as is claimed.

Administration, Oral↗

PubMed1987

Influence of cardiac function on the diuretic and hemodynamic effects of the loop diuretic piretanide.

The influence of cardiac function on the diuretic and hemodynamic effects of the loop diuretic piretanide was investigated in nine patients with congestive heart failure. The diuretic response to piretanide correlated significantly with the pretreatment cardiac index (r = 0.90). Furthermore, a significant correlation was found between the pretreatment fractional sodium excretion and the cardiac index (r = 0.85). The fractional sodium excretion is reciprocal to the renal sodium and water reabsorption. No change in the hemodynamics was observed prior to the onset of diuresis. At 120 minutes after administration of piretanide, the reduction of mean pulmonary capillary wedge pressure (r = 0.88) and mean right atrial pressure (r = 0.80) was significantly related to the diuretic response. We conclude that the reduced diuretic response to piretanide in patients with low cardiac index is due to increased renal sodium and water reabsorption. The hemodynamic changes following the administration of piretanide are dependent on the diuresis.

Adult↗

PubMed1992

[Azosemide--a loop diuretic with protracted effect].

Azosemide, a novel loop diuretic that has been available for the past few years, acts qualitatively like thiazide, viz by prolonging the diuretic effect with, however, only a slight delay in the onset of diuresis, in combination with the quantitative effect of previous loop diuretics, i.e. large excretion volumes. On the basis of experience gained to date, specific indications will presumably be cardiac and renal edema and ascites, also as long-term treatment. Provided that no NaCl or volume deficiency presents, side effects are insignificant.

Diuretics↗

PubMed1983

Dose-dependent reduction in renal magnesium clearance by amiloride during frusemide-induced diuresis in rats.

The effects of the potassium-sparing diuretic, amiloride, on fractional magnesium excretion were investigated at four doses (0.02, 0.08, 0.20 and 2.00 mg kg-1 h-1) during frusemide-induced diuresis. Amiloride caused a dose-dependent reduction in the fractional excretion of both magnesium and potassium, whereas the effects of amiloride, over the same dose range, on fractional sodium and calcium excretion were not dose-dependent. The results indicate that amiloride exerted a specific renal action to alter magnesium and potassium transport dissociated from effects on sodium excretion.

Amiloride↗

PubMed1986

Mannitol concentrations in blood plasma in connection with transurethral resection of the prostate using mannitol solution as an irrigating fluid.

Thirteen patients undergoing transurethral resections of the prostate (TURP) using iso-osmolar 5% mannitol as an irrigating fluid were studied. Mannitol was determined in serum (plasma), as were sodium, prostatic acid phosphatase protein (PAP) and osmolality as probable indicators of absorption of irrigating fluid. The plasma level of mannitol (mean 2.7 g/l = 15 mmol/l) immediately postoperatively, the increase in serum PAP (mean 93 micrograms/l) and the decrease in serum sodium (mean 8.7 mmol/l) all reflect the amount of irrigating fluid absorbed during TURP. The three variables are intercorrelated. The plasma osmolality was unchanged (mean -1 mosmol/kg). A small but constant fraction of mannitol was found in the erythrocytes 2 hours after the operation, amounting to about 3% of the simultaneous plasma concentration. The mean plasma half-life of mannitol was 127 min in the absence of uraemia. In two cases showing a slight increase in serum creatinine the half-lives were prolonged. An estimate of the volume of fluid absorbed was made from the observed plasma mannitol levels. A fluid absorption of up to 3 litres (mean 1.1 l) was found. A strong diuretic effect was observed in some cases when irrigation with mannitol was combined with i.v. furosemide. We conclude that the i.v. diuretic should be withheld until the extent of fluid absorption has been estimated. If the sodium concentration in the serum is largely unchanged immediately postoperatively, diuresis can be induced by an intravenous diuretic.

Absorption↗

PubMed1985

Effects of opiates on urine output in the water-loaded rat and reversal by beta-funaltrexamine.

The effects of several mu and kappa opioid receptor agonists on urinary excretion were examined in the water-loaded rat. Mu agonists induced anti-diuresis whereas kappa agonists caused diuresis. Furthermore, high efficacy kappa agonists eg. U50, 488H and tifluadom, produced marked diuretic effects, whereas kappa partial agonists eg. nalorphine, produced low maximum diuresis. Compounds having activity at both mu and kappa receptors eg. ethylketocyclazocine(EKC) and MR2034, produced a biphasic effect, an initial anti-diuretic effect followed by a more sustained diuretic effect. The irreversible mu receptor antagonist, beta-funaltrexamine (beta-FNA) antagonized the anti-diuretic effects elicited by fentanyl, pentazocine and buprenorphine and the initial anti-diuretic effect induced by EKC but did not inhibit the diuretic effects induced by U50, 488H and EKC. Thus, the use of beta-FNA in the water-loaded rat provides us with a valuable in vivo test which differentiates both mixed and selective opioid receptor agonists.

Animals↗

PubMed1998

Effects of diuretics on renal kallikrein gene expression in rats.

1. To determine the effects of diuresis and changes in electrolyte balance on kallikrein gene expression, renal kallikrein mRNA levels were correlated with urine volumes, urinary electrolyte levels, haematocrit and plasma electrolyte levels in rats treated with substances with a range of diuretic activities. 2. Furosemide and related compounds, benzyl furosemide and isofurosemide, as well as amiloride hydrochloride, chlorothiazide or the vehicle (saline) were administered twice daily for 24 or 72 h to rats housed in metabolic cages. 3. Diuresis occurred after each treatment with furosemide, after the initial treatment with benzyl furosemide and did not occur after isofurosemide, amiloride hydrochloride or chlorothiazide. 4. Kallikrein gene expression in kidney was increased after 72 h treatment with furosemide, after 24 or 72 h treatment with benzyl furosemide or amiloride hydrochloride and was unchanged after 24 or 72 h treatment with isofurosemide or chlorothiazide, compared with vehicle-treated controls. 5. Plasma urea levels were elevated after 72 h treatment with furosemide, benzyl furosemide and chlorothiazide and plasma chloride was decreased after 24 and 72 h benzyl furosemide. Haematocrits were unchanged. There were no changes in urinary electrolyte levels 72 h after treatment with any of the diuretics. 6. Neither diuresis nor measurable changes in plasma or urinary electrolytes correlate with changes in renal kallikrein gene expression after diuretic treatment of rats.

Animals↗

PubMed1999

[Evaluation of acute renal insufficiency in Dakar].

The acute renal failure (ARF) is a serious complication occurring commonly in gravidic toxemia. The aim of this retrospective study was to evaluate the treatments wed on patients presenting an ARF and hospitalized in the Dakar hemodialysis centers and emergency service of Hospital Principal. These patients should be aged over 15 years at present no history of chronic renal failure. The diagnosis of ARF was based on the presence of a creatinine clearance value < or = 80 ml/mn, a creatinemia > 176.8 mo/l, an azotemia > 9.99 mmol/l. Thirty patients aged form 16 to 56 years were studied, they were 6 males and 24 females. Among them, 22 (73.33%) present anuria, 5 (16.7%) were in oligo anuria, and 3 (10%) had a normal diuresis. An aetiologic treatment was instituted whenever necessary. The other treatments consisted in dietary measures, hydroelectrolytic balance, blood transfusion, diuretic therapy, and hemodialysis. All anuric patients had a diuretic regimen. Ten of them had recovered a diuresis, 16 underwent hemodialysis in a mean time of 4 days. None of latter recovered renal function 5 patients developed Chronic renal failure and 11 died, mainly by infectious complications. Acute renal failure has until now a poor prognosis in our regions because of a certain management delay. This management should include a guide and adequate volume replacement, and eventually diuretic therapy, and dialysis as soon as possible.

Acute Kidney Injury↗

PubMed1989

Efficacy and pharmacokinetics of piretanide in patients with congestive heart failure.

The efficacy and pharmacokinetics of the diuretic piretanide were studied in two groups of six patients hospitalized for congestive heart failure. A dosage of 2 x 6 mg day-1 to 2 x 12 mg day-1 of intravenous piretanide for 7 days was sufficient to abrogate most symptoms of cardiac insufficiency. When compared with another group of healthy volunteers, patients with congestive heart failure had reduced total body clearance of piretanide of about 50% which was attributable to a diminished renal but not non-renal clearance. The analysis of the interrelationship between urinary piretanide excretion and diuresis by means of a linearized Emax-model revealed a maximal diuresis of 231 ml h-1 and a urinary piretanide excretion to induce half-maximal diuresis of 245 micrograms h-1. Thus patients with congestive heart failure exhibit a decreased renal clearance of piretanide and a good response to this high ceiling diuretic after intravenous dosing.

Aged↗