SEARCH · PubMed Health

Results for “FUROSEMIDE”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 325 records · Page 18Linked to original sources

PubMed1988

Different effects of furosemide on alpha-adrenoceptors and on platelet aggregation in man.

The effect of a long-term administration of furosemide (2 x 30 mg/day for 3 weeks) on platelet alpha 2-adrenoceptor density and the fraction of high-affinity binding sites, as well as on platelet aggregation induced by adrenaline and ADP, was studied ex vivo in 8 normotensive volunteers. For comparison the in vitro effect of furosemide on platelet aggregation was also evaluated. Furosemide decreased alpha 2-adrenoceptor-density (P less than 0.01) and the fraction of high-affinity binding sites (P less than 0.05). Adrenaline-induced platelet aggregation was not altered ex vivo and in vitro. Furosemide inhibited ADP-induced platelet aggregation ex vivo (P less than 0.05) and in parallel in vitro (P less than 0.01) in a dose-dependent manner. The reduction of the density of alpha 2-adrenoceptors in the high affinity state may be of functional importance for the hemodynamic effects of furosemide. The inhibitory effect of furosemide on ADP-induced platelet aggregation ex vivo and in vitro, which is not related to the effects on adrenoceptors, seems to involve direct effects of furosemide on platelet function. It remains to be seen whether the latter effect is of clinical importance.

Adult↗

PubMed1976

The effects of furosemide on remal blood flow and cortical perfusion during methoxyflurane and halothane anaesthesia.

Nephrotoxicity due to methoxyflurane may be due in part to alterations in intra-renal perfusion. Furosemide is believed to alter the intra-renal distribution of blood flow. Studies have been carried out to observe the effects of systemic furosemide administration during methoxyflurane and halothane anaesthesia in normotensive animals and in animals made hypotensive by increasing inspired concentrations of the anaesthetics. During halothane anaesthesia normotensive dogs showed a rise in total renal blood flow during the infusion of furosemide. Hypotensive dogs showed no increase in flow. During methoxyflurane anaesthesia no change in total renal blood flow followed furosemide administration to normotensive animals. Some diminution in total blood flow followed the administration of furosemide in hypotensive dogs during methoxyflurane anaesthesia. In normotensive dogs during halothane anaesthesia there was a significant increase in deep cortical perfusion after furosemide. Furosemide, therefore, is unlikely to mitigate the potential for nephrotoxicity which methoxyflurane possesses. Furthermore, this diuretic may adversely influence renal function when administered during halothane anaesthesia.

Anesthesia, Inhalation↗

PubMed2003

Parallel down-regulation of chloride channel CLC-K1 and barttin mRNA in the thin ascending limb of the rat nephron by furosemide.

In the past few years the pivotal role of kidney Cl(-)channels (ClC-K) channels in maintaining salt and water homeostasis in the kidney has been established. The aim of the present study was to investigate the influence of the loop diuretic furosemide on the gene expression of the kidney chloride channel ClC-K1 and its recently described functional subunit barttin. Male Sprague Dawley rats received the loop diuretic furosemide (12 mg/kg/day) for 6 days. Rats had free access to 0.9% NaCl, 0.1%KCl solution to prevent volume depletion. Localisation and regulation of ClC-K1 and barttin mRNA was analysed by RNase protection and in situ hybridisation. Nephron-specific regulation was investigated by microdissection and real-time PCR quantification. In furosemide-treated rats ClC-K1 mRNA decreased to half in the inner medulla. In the renal cortex and outer medulla ClC-K1 mRNA levels were weak and did not change. Under furosemide treatment barttin mRNA was regulated in parallel with ClC-K1 mRNA. A significant mRNA decrease occurred after furosemide treatment in inner medulla (0.50 fold), whereas cortical and outer medulla levels remained unaffected. (35)S in situ hybridisation confirmed the regulation and distribution seen in the RNase protection assay experiments. Microdissection of the inner medullary collecting duct and thin limb of Henle's loop followed by real-time PCR revealed that CLC-K1 and barttin mRNA regulation in inner medulla was limited to the thin limb; mRNA levels in collecting ducts were not affected by furosemide treatment. Our findings imply that during furosemide treatment selective down-regulation of ClC-K1 and barttin mRNAs in thin limb plays a role in maintaining salt and water homeostasis.

Actins↗

PubMed1988

Intrarenal thromboxane A2 generation reduces the furosemide-induced sodium and water diuresis in cirrhosis with ascites.

To assess the effects of intrarenal thromboxane A2 generation on furosemide-induced sodium and water excretion we administered furosemide (40 mg i.v.) to 8 nonazotemic cirrhotic patients with ascites and 8 healthy subjects before and after the administration of OKY 046 (200 mg twice orally), a powerful thromboxane-synthase inhibitor. Selective thromboxane-synthase inhibition significantly reduced basal and postfurosemide (1 h) urinary thromboxane B2 excretion in healthy subjects (65% before and 62% after furosemide) as well as in cirrhotic patients (52% before and 67% after furosemide) without affecting urinary prostaglandin E2 and 6-keto prostaglandin F1 alpha excretion. During the first hour after furosemide administration, OKY 046 administration significantly enhanced postfurosemide water excretion (milliliters per minute) in both healthy subjects (from 8.5 +/- 2.0 to 11.6 +/- 2.1, p less than 0.001) and cirrhotic patients (from 1.1 +/- 0.8 to 4.2 +/- 0.5, p less than 0.005), whereas furesemide-induced natriuresis (microequivalents per minute) was significantly increased only in the latter group (from 973 +/- 125 to 1405 +/- 121, p less than 0.05). Our data indicate that intrarenal thromboxane A2 generation, elicited by furosemide administration, may reduce the effects of the drug on water and sodium diuresis. Such a reduction seems to be more marked in the presence of an activated intrarenal prostaglandin system, suggesting that renal thromboxane A2 may represent an additional factor in conditioning the impaired responsiveness to furosemide, which is frequently observed in cirrhotic patients with ascites.

6-Ketoprostaglandin F1 alpha↗

PubMed1990

Chronopharmacological study of furosemide; (VI). Influence of prolonged exposure to continuous light.

We have previously reported that a time-dependent variability is observed in the diuretic effects of furosemide in rats. The present study was undertaken to examine the influence of prolonged exposure to continuous light on chronopharmacological profiles of furosemide in Wistar rats. In study I, rats were maintained for more than 2 weeks under conditions of light (0700-1900 hrs) and dark (1900-0700 hrs) (L-D). Furosemide (30 mg/kg) was orally given at 1200 hrs or at 2400 hrs. Urine was collected for 8 hours after the drug and urinary excretion of sodium and furosemide were determined respectively. Thereafter, these rats were exposed to continuous light (L-L) for the next 4 weeks, and were again maintained under the L-D cycle. The identical trial of study I was repeated at the end of the L-L (study II) and the second L-D (study III) conditions. Urine volume and urinary excretion of sodium and furosemide following the drug were significantly greater at 1200 hrs than at 2400 hrs under conditions of L-D (study I and III). However these administration time-dependent changes in the effects of furosemide and its urinary amount disappeared with L-L condition (study II). These findings indicate that the mode of the time-dependent changes in the effects of furosemide is altered by prolonged exposure to continuous light.

Animals↗

PubMed1990

Chronopharmacological study of furosemide; (IV). Examination in aged rats.

We have previously reported that a time-dependent variability is observed in the diuretic effects of furosemide in young Wistar rats. The present study was undertaken to examine the influence of ageing on chronopharmacological profiles of furosemide in rats. Furosemide (5 mg/kg) was injected intra-arterially in young (10-11 week old) and aged (21-22 month old) Wistar rats at 1000 hrs or at 2200 hrs. Urine was collected for 60 min after the drug and urinary excretion of sodium and furosemide were determined respectively. Urine volume and urinary excretion of sodium and furosemide following the drug injection were significantly greater at 1000 hrs than at 2200 hrs in the young rats as observed in the previous study. However these administration time-dependent changes in the effects of furosemide and its urinary amount disappeared in the aged rats. These findings indicate that the mode of the time-dependent changes in the effects of furosemide is altered in aged Wistar rats.

Aging↗

PubMed1992

Influence of renal denervation on chronopharmacology of furosemide in rats.

Our previous studies have suggested that the adrenergic nervous system is involved in the mechanism responsible for the time-dependent change in the urinary excretion of furosemide in rats. To examine a potential role of renal nerves in this phenomenon, renal denervation or sham operation was performed using unilaterally nephrectomized rats. Furosemide (30 mg/kg) was given orally at 12 am or 12 pm. Urine was collected for 8 hours after furosemide dosing, and urinary excretions of furosemide and sodium were determined. Urinary furosemide excretion and diuretic effects of the agent (urine volume and urinary sodium) were significantly greater at 12 am than at 12 pm in the sham-operated group of rats. However these administration time-dependent changes in urinary furosemide and its diuretic effects disappeared in the renal-denervated group of animals. These results suggest that the renal nerves contribute to the time-dependent changes in the urinary excretion of furosemide and its subsequent diuretic effects.

Administration, Oral↗

PubMed1993

Influence of clorgyline treatment on chronopharmacology of furosemide in rats.

Circadian variations in the adrenergic nervous system have been reported to be altered by chronic treatment with clorgyline, a monoamine-oxidase inhibitor. In the present study, the influence of clorgyline on the chronopharmacology of furosemide, a loop diuretic agent, was examined in rats maintained under conditions of light from 7 am to 7 pm and dark from 7 pm to 7 am. Clorgyline (4 mg/kg/day) or its vehicle alone was infused subcutaneously by osmotic minipumps for 14 days. Furosemide (30 mg/kg) was given orally at 12 am [noon (N)] or 12 pm [midnight (M)]. Urine was collected for 8 hours after the agent, and urinary excretions of sodium and furosemide were determined. Urine volume and urinary excretions of sodium and furosemide were significantly greater at 12 N than at 12 M in the vehicle-infused group of rats. However these administration time-dependent changes in the effects of furosemide and its urinary excretion disappeared in the clorgyline-infused animals. These results suggest that the mode of the diurnal variation in the effects of furosemide is altered by chronic treatment with clorgyline. As chronic clorgyline is considered to disturb the adrenergic nervous system, the present findings are compatible with the hypothesis that this system is involved in the mechanism responsible for the time-dependent change in the effects of furosemide.

Analysis of Variance↗

PubMed1994

Effect of angiotensin II type 1 receptor antagonist on urinary prostaglandin E2 excretion following furosemide in rats.

The present study was undertaken to examine an effect of an angiotensin II type 1 (AT1) receptor antagonist on urinary prostaglandin E2 (PGE2) excretion following furosemide, a loop diuretic, in rats. Furosemide (30 mg/kg) was given orally with or without pretreatment with derapril (30 mg/kg), an angiotensin converting enzyme inhibitor, TCV-116 (1 mg/kg), an AT1 receptor antagonist, or losartan (10 mg/kg), another AT1 receptor antagonist. The 6-hour urine was collected following furosemide, and the urinary excretion of PGE2 was determined. The urinary PGE2 increased significantly following furosemide alone. However, such a furosemide-induced increase was not observed with pretreatment with derapril, TCV-116 or losartan. These results suggest that the increased urinary excretion of PGE2 following furosemide is blunted by derapril, TCV-116 and losartan. As TCV-116 and losartan are selective AT1 receptor antagonists, the effect of furosemide on renal PGE2 production, as reflected by the urinary PGE2, might be mediated by an activation of AT1 receptors.

Angiotensin II↗

PubMed1983

Effects of acute metabolic acid-base changes and furosemide on magnesium excretion in rats.

The effect of acute metabolic acid-base changes on renal magnesium transport is not well defined. We have examined renal magnesium handling in three groups of ten acutely thyroparathyroidectomized rats infused with isotonic NaCl (controls), NH4Cl (acidosis), and NaHCO3 (alkalosis). To define the interactions of furosemide with acid-base changes and in an attempt to localize the site of action of acidosis and alkalosis on tubular magnesium transport, the rats were studied in a second phase after administration of a maximal dose of furosemide. Before furosemide, the blood pH was 7.40 in the controls, 7.27 (P less than 0.001) in the acidotic rats, and 7.56 (P less than 0.001) in the alkalotic rats. The filtered magnesium load was not significantly different in the three groups, but fractional excretion of magnesium (FEMg) was 33.7%, 37.4%, and 13.3% in the controls, the acidosis group, and the alkalosis group, respectively. Following furosemide, the blood pH was unchanged in each group, but FEMg increased significantly to 55.4%, 71.1% (P less than 0.01 compared with controls), and 41.4% (P less than 0.01 compared with controls) in the controls, the acidotic rats, and the alkalotic rats, respectively. These data indicate that metabolic alkalosis per se enhances renal magnesium transport, and this effect is also evident after blockade of loop magnesium reabsorption by a maximal dose of furosemide. Acidosis per se does not significantly alter magnesium transport, but an inhibitory effect of acidosis on magnesium reabsorption becomes evident when distal magnesium delivery is greatly increased by furosemide. These interactions suggest that metabolic acid-base changes and furosemide may influence magnesium reabsorption at different tubule sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Imbalance↗

PubMed1990

Effect of inhaled furosemide on the bronchial response to methacholine and cold-air hyperventilation challenges.

Inhaled furosemide has been recently demonstrated to inhibit the bronchoconstrictive effects of exercise, ultrasonically nebulized distilled water, and antigen challenge. The presumed mechanism of action of these challenges is through mast cell degranulation. We report on the effect of inhaled furosemide on cold-air hyperventilation challenge (CAHC) and methacholine challenge. We studied 10 subjects with mild to moderate asthma in a double-blind, placebo-controlled, crossover study. Inhaled furosemide did not affect FEV1 in the hour after inhalation, and there was no significant difference between placebo or furosemide on the dose of methacholine causing a 20% fall in FEV1. Our results demonstrated inhaled furosemide significantly attenuated the bronchoconstrictive effect at 6 and 9 minutes after CAHC (p less than 0.05 and 0.029, respectively) when furosemide was compared to placebo and approached significance at 12 and 15 minutes after CAHC (p = 0.052 and 0.56, respectively). Inhaled furosemide attenuates CAHC but does not effect methacholine-induced bronchoconstriction.

Administration, Inhalation↗

PubMed1986

Pharmacokinetics and pharmacodynamics of furosemide in geriatric patients.

Twenty geriatric patients with multiple diseases were administered a single intravenous dose of 40 mg furosemide. Furosemide plasma and urine concentrations were measured using a thin-layer chromatography method and were fitted to an open 2-compartment model. Furosemide half-life was prolonged two-fold in the elderly patients compared with a control group of younger adults. In the same way renal clearance and total clearance were markedly reduced in the geriatric group. The non-renal clearance and the volume of distribution were not significantly altered. There were many significant correlations between clinical and biochemical data and pharmacokinetic parameters, especially between blood pressure and the area under the curve (AUC O-infinity), total clearance and non-renal clearance of furosemide. Our data suggest a special function of alpha-2-globulins in binding of furosemide. Renal function (i.e. creatinine clearance) was shown to be an important parameter for estimating the elimination rate of furosemide. In addition, pharmacodynamic action (volume of excreted urine) was closely correlated with the elimination rate: furosemide is apparently triggering its own elimination.

Aged↗

PubMed1992

Effect of furosemide treatment on the central and peripheral pressor responses to cholinergic and adrenergic agonists, angiotensin II, hypertonic solution and vasopressin.

The present study was performed to investigate the effect of treatment with furosemide on the pressor response induced by intracerebroventricular (i.c.v.) injections of cholinergic (carbachol) and adrenergic (norepinephrine) agonists, angiotensin II (ANGII) and hypertonic saline (HS, 2 M NaCl). The changes induced by furosemide treatment on the pressor response to intravenous (i.v.) norepinephrine, ANGII and arginine vasopressin (AVP) were also studied. Rats with a stainless-steel cannula implanted into the lateral ventricle (LV) were used. Two injections of furosemide (30 mg/kg b.wt. each) were performed 12 and 1 h before the experiments. Treatment with furosemide reduced the pressor response induced by carbachol, norepinephrine and ANGII i.c.v., but no change was observed in the pressor response to i.c.v. 2 M NaCl. The pressor response to i.v. ANGII and norepinephrine, but not AVP, was also reduced after treatment with furosemide. These results show that the treatment with furosemide impairs the pressor responses induced by central or peripheral administration of adrenergic agonist or ANGII, as well as those induced by central cholinergic activation. The results suggest that the treatment with furosemide impairs central and peripheral pressor responses mediated by sympathetic activation and ANGII, but not those produced by AVP.

Angiotensin II↗

PubMed1989

The time-course of furosemide-induced strial changes in guinea pigs after pretreatment with daltroban.

It was shown previously (Ernst et al., 1989) that pretreatment of guinea pigs with a thromboxane (TX) receptor antagonist attenuates the decline of the endocochlear potential (EP) induced by furosemide. The present paper is aimed at investigating a possible correlation between the electrophysiological data and ultrastructural changes of the stria vascularis by electron microscopy. The dosages of 40, 60, and 80 mg/kg furosemide were injected after the pretreatment with the TX receptor antagonist daltroban and compared to controls which were injected with furosemide only. It was found at all furosemide concentrations that the strial changes 10 min after injection were nearly unchanged against controls. 30 min after furosemide injection, the most pronounced changes were seen when pretreating the animals: a clear reduction of the marginal cell swelling and edema in general were observed at 40 and 60 mg/kg furosemide. The guinea pigs injected with 80 mg/kg furosemide after pretreatment displayed nearly the same changes as controls.

Animals↗

PubMed1992

Effects of organic acids on the edema of the stria vascularis induced by furosemide.

Furosemide is a loop diuretic which is ototoxic. Investigations have shown the stria vascularis to be the target tissue of this ototoxic drug. The purpose of the present study was to investigate the effects of furosemide on the stria vascularis in chinchillas, in controls and in animals pretreated with the above organic acids. Control animals were injected with 0.5 ml alkalinized saline followed by furosemide IV 30 min later. Experimental animals received probenecid, penicillin or sodium salicylate IV. Thirty minutes later, furosemide was injected in the same dose as in the controls. The basal turn of the stria vascularis was rapidly removed at various times from 10 to 30 min after furosemide administration and processed for transmission electron microscopy. Control animals were found to have reversible edema of the stria vascularis. Experimental animals had variable findings. Those animals pretreated with penicillin had virtually no edema of the stria vascularis at any time. Salicylate and probenecid pretreated animals had significantly less edema from one to 10 min after furosemide injection, but more edema than controls at later times. These findings suggest a discrepancy between ultrastructural pathology and functional status of the cochlea in experimental animals pretreated with probenecid or sodium salicylate followed by furosemide. On the other hand, good structure function correlations were seen in controls and in experimental animals pretreated with penicillin.

Acids↗

PubMed1990

Evaluation of high performance liquid chromatography (HPLC), enzyme linked immunosorbent assay (ELISA) and particle concentration fluorescence immunoassay (PCFIA) methods for the screening, quantitation and pharmacokinetic study of furosemide in horses.

Equine plasma and urine samples were analyzed by using a high-performance liquid chromatography (HPLC), enzyme-linked immunosorbent assay (ELISA) and particle concentration fluorescence assay (PCFIA). Although ELISA and PCFIA were rapid, simple and sensitive for the screening of furosemide, they did not give reproducible quantitative results. The HPLC method, which required relatively longer analysis time, provided simple and reproducible quantitative analysis of furosemide in plasma and urine. The performance of the three methods was compared for the quantitation of furosemide in plasma obtained from thoroughbred mares dosed intravenously with furosemide (500 micrograms/kg (n = 7) and 1.0 mg/kg (n = 5)). Although the plasma furosemide profiles determined by ELISA, PCFIA and HPLC were similar, ELISA and PCFIA methods exhibited considerable variation in values. At high furosemide concentrations, the PCFIA method gave better quantitative values than ELISA. However, at trace furosemide concentrations the PCFIA method gave false positive values which were not confirmed by HPLC or ELISA. The pharmacokinetic values obtained from the HPLC data and the pharmacokinetic values obtained previously from the gas chromatographic data were comparable. The data obtained by ELISA and PCFIA were not suitable for the pharmacokinetic calculations.

Animals↗

PubMed2003

Backdoor phosphorylation of basolateral plasma membranes of small intestinal epithelial cells: characterization of a furosemide-induced phosphoprotein related to the second sodium pump.

Enterocyte has two different Na+-stimulated ATPases, the ouabain-sensitive Na+/K+ ATPase and a furosemide-inhibitable Na+ ATPase. To identify the polypeptide associated with the Na+-ATPase, 32Pi phosphorylation into basolateral membranes of enterocyte was investigated. Both, ouabain and furosemide induced Mg2+-dependent, vanadate-sensitive 32Pi incorporation into a 100kDa polypeptide. K(m) for Pi was 17.7+/-1.82 microM and 16.8+/-0.69 microM for ouabain-induced and furosemide-induced phosphorylation, respectively. K(m) for furosemide was 1.3+/-0.21 mM. Furosemide-induced 32Pi incorporation was sensitive to alkaline pH and hydroxylamine suggesting an acyl-phosphate bond. Na+ and K+ inhibited 32Pi incorporation induced by ouabain. In contrast, Na+ stimulated furosemide-induced phosphorylation with a K(m) of 16.5+/-5.59 mM while K+ had no effect. Purified Na+/K+ ATPase only presented ouabain-induced phosphoprotein, indicating that furosemide-induced phosphorylation is not related to this enzyme and appears to correspond to a new member of P-type ATPases associated with the second Na+ pump.

Animals↗

PubMed2000

Furosemide withdrawal in elderly heart failure patients with preserved left ventricular systolic function.

To explore the possibilities of furosemide withdrawal in elderly heart failure (HF) patients with intact left ventricular (LV) systolic function and assess its effects on functional status and orthostatic blood pressure homeostasis, we performed a placebo-controlled pilot trial of furosemide withdrawal with 3 months of follow-up in 32 HF patients (aged 75.1 +/- 0.7 years [mean +/- SEM]) with a LV ejection fraction of 60 +/- 2% and without overt congestion. Investigations included repeated clinical assessment, spirometry, standardized 6-minute walking test, and chest x-rays. Measurements of blood pressure response on active standing and Doppler echocardiography were performed before and 3 months after furosemide withdrawal. Recurrent congestive HF occurred in 2 of 21 patients (10%) who discontinued furosemide use, and in 1 of 11 patients (9%) who continued furosemide (p = NS). Three patients restarted furosemide for ankle edema and 1 for blood pressure levels >180/100 mm Hg. After 3 months, there were no differences regarding HF symptom scores, blood pressure, heart rate, spirometric results, 6-minute walking distance, or quality of life scores between patients who discontinued use and patients who continued the therapy. In patients successfully withdrawn, Doppler E/A ratio increased from 0.68 +/- 0.05 to 0.79 +/- 0.06 after withdrawal (p <0.01), and maximum blood pressure decrease on active standing changed from -8 +/- 5 mm Hg to +5 +/- 3 mm Hg systolic (p <0.05). Thus, in this pilot investigation of furosemide withdrawal in elderly HF patients without overt congestion and with a normal LV systolic function, withdrawal was successful in almost all patients and was associated with improvement of LV diastolic filling and blood pressure homeostasis on active standing.

Aged↗