Treatment of the syndrome of inappropriate secretion of antidiuretic hormone by long loop diuretics.
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Adolescent↗
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Efficacy and safety of a furosemide continuous infusion following cardiac surgery.
OBJECTIVE: To review the literature regarding the efficacy and safety of continuous intravenous infusion of loop diuretics following cardiac surgery. DATA SOURCES: Articles were identified through a MEDLINE search (1966-March 2006) using the key words furosemide, bumetanide, torsemide, ethacrynic acid, loop diuretics, continuous infusions, intravenous infusions, surgery, cardiac surgery, cardiovascular surgery, and thoracic surgery. Search results were limited to studies in human subjects published in English. Additional references were identified through review of the bibliographies of the articles cited. STUDY SELECTION AND DATA EXTRACTION: All clinical trials and observational reports identified that evaluated or described the efficacy and/or safety of a continuous infusion of a loop diuretic in adult or pediatric patients who had undergone cardiac surgery were included in this review. DATA SYNTHESIS: Loop diuretics are often used to promote diuresis following cardiac surgery. Studies in patients who have undergone cardiac surgery have demonstrated that a more consistent and sustained diuresis is produced by a continuous infusion of furosemide compared with intermittent bolus doses of furosemide. However, there does not appear to be a significant difference in total urine output or change in serum electrolyte levels when furosemide is administered as a continuous infusion compared with intermittent bolus doses. CONCLUSIONS: A continuous infusion of furosemide is an effective and safe method of diuresis in patients undergoing cardiac surgery.
Arrhythmias, Cardiac↗
Pedal manifestations of hyperuricemia due to thiazide diuresis.
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Diuretics↗
Experimental gentamicin nephrotoxicity: effect of streptozotocin-induced diabetes.
To determine the effect of diabetes mellitus on gentamicin nephrotoxicity we treated male F344 rats with streptozotocin 22 mg/kg (DM rats). DM rats were compared to controls (C) and nondiabetic rats ingesting the osmotic diuretic isosorbide administered to simulate glycosuric diuresis (C/I). Base-line C/I renal function and histology did not differ from C. However, in DM rats base-line inulin clearance (CIN) was 20% lower, and renal cortical slice uptake of p-aminohippurate was reduced compared to C and C/I. DM rats also had foci of renal tubular epithelial dysplasia not seen in C or C/I. Gentamicin was administered at 40 mg/kg-day to C and C/I and 32 mg/kg-day to DM rats to adjust for base-line CIN. Acute tubular necrosis, associated with depression of CIN and renal cortical p-aminohippurate and N-methylnicotinamide uptake, developed in all three groups. There were no differences between C and C/I. However, the degree of acute tubular necrosis and dysfunction was less in DM rats than C and C/I. Renal cortical gentamicin accumulation was also slower in DM than either C or C/I, and changes in renal cortical gentamicin over time followed a different pattern in DM rats. These results indicate that 1) attenuation of gentamicin injury in DM rats may be related to reduced accumulation of gentamicin by the renal cortex, 2) this reduced accumulation may be due to subtle baseline tubular injury mediated by streptozotocin or the diabetic state, and 3) osmotic diuresis does not account for attenuation of renal injury in DM.
Animals↗
Caution in the use of volume expansion diuretic renal scan.
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Diuresis↗
The use of arginine vasopressin measurements in the polyuric dog.
The direct measurements of AVP during water deprivation and salt loading demonstrate the inability of the direct water deprivation test to distinguish accurately between several forms of polyuria. Polyuria and polydipsia are commonly formed disorders in the dog and can be caused by osmotic diuresis; deficient release of anti-diuretic hormone-arginine vasopressin (AVP); a decreased renal response to AVP; excessive water intake. The differentiation between these forms often requires a water deprivation test followed by administration of vasopressin. The latter test is an indirect one and relies upon changes in urinary concentration as index of vasopressin function. With this it is usually possible to differentiate total neurogenic diabetes insipidus and total nephrogenic diabetes insipidus. However, several dipsogenic forms and partial diabetes insipidus forms are still very difficult to distinguish from each other and only the direct measurement of plasma AVP (PAVP) can give conclusive information. The role of AVP in osmoregulation was investigated by measuring plasma osmolality (Posm) and PAVP during; hypertonic saline infusions; water deprivation in both healthy experimental dogs and in dogs with polyuria.
Animals↗
[Renal excretion of cations by the lamprey Lampetra fluviatillis under the influence of diuretics].
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Animals↗
Renal nerve and alpha 2-adrenergic action during acute volume expansion in the anaesthetized rat.
1. The effects of renal denervation and alpha 2-adrenoceptor blockade on diuresis and natriuresis in response to acute volume expansion (VE) were investigated in anaesthetized rats. 2. In normal rats, a 30 min intravascular VE of up to 7.5% of bodyweight caused a significant diuresis and natriuresis. 3. Denervation enhanced the diuretic effect of VE by 39%, while alpha 2 blockade by 12 mumol/kg per h rauwolscine significantly inhibited the response by 61% in innervated kidneys and 43% in denervated kidneys. 4. Similar results were found for natriuresis in both innervated and denervated kidneys. 5. The results demonstrate that renal sympathetic nerve activity inhibits part of the increase in sodium and water excretion caused by VE, since denervation increased excretion under these conditions. The contribution of renal nerves to the control of renal function, however, decreases during the response to VE. 6. alpha 2-Adrenoceptor action enhanced the diuretic and natriuretic effects of VE by mechanisms otherwise unrelated to renal nerve activity.
Anesthesia↗
The influence of furosemide on free water clearance.
BACKGROUND: Laboratory measurements of osmolality and electrolyte concentrations are useful as a source of clinical and pathophysiologic information on kidney function. We obtained different conditions of baseline diuresis in 54 rats, which were then treated with furosemide 10 mg/kg. From measurements of plasma (P) and urine (U) osmolality and Na, we calculated the free water clearance (CH2O) and the contributions of Na+ and non-Na(+)-solutes to its changes during diuretic administration. RESULTS: The results show that furosemide abolishes both urine diluting and concentrating ability, by reducing the contribution of non-Na(+)-solutes to Uosm and the formation of CH2O, while the contribution of Na+ to Posm remains unchanged. During furosemide the urines approach isosmoticity irrespective of the baseline Uosm with an asymptomatic function similar to that imposed by osmotic diuresis. It is suggested that the overflow to the concentrating sites of the nephron overwhelms their normal transport capacity independently of their baseline water permeability. The disruption of the transepithelial osmotic gradient caused by the drug impairs the transepithelial osmotic flow, leading to the excretion of isosmotic urines. CONCLUSIONS: The effect of non-Na(+)-solutes in the laboratory measurement of urine constituents can be reduced to that of plasma determination by diluting the urines according to empiric formulas derived from the present data.
Animals↗
On the diuretic action produced dibutyryl cyclic AMP in dogs.
Experiments were undertaken on order to elucidate the mechanism of diuresis induced by dibutyryl cyclic AMP in dogs. Intravenous injections of dibutyryl cyclic AMP produced an increase in urine flow in dogs hydrated with saline. It was also noted that dibutyryl cyclic AMP produced an increase in myocardial contraction, renal blood flow and glomerular filtration rate; In addition, unilateral injection of dibutyryl cyclic AMP into the left renal artery produced diuresis bilaterally. Based on the above findings it was suggested that the diuretic action induced by dibutyryl cyclic AMP is associated with its hemodynamic effect.
Animals↗
Decreased diuretic response to furosemide in rats with acute hepatic failure.
Furosemide diuresis is occasionally reduced in cirrhotic patients with ascites. To define this phenomenon, the amounts of water, electrolytes, and furosemide excreted in urine were measured in control and CCl4-induced acute hepatic failure (AHF) rats. The diuretic action of furosemide (10 mg/kg, i.v.) was reduced in AHF rats, accompanied by increased plasma aldosterone concentration and accelerated urinary K+ excretion rate. Furosemide transiently increased the urinary inulin excretion rate (UVIN) in both control and AHF rats. Then the UVIN quickly returned to the baseline value in control rats, but rapidly dropped below the baseline in AHF rats. To clarify the contribution of aldosterone in these phenomena, AHF rats was adrenalectomized (ADX) and treated with or without exogenous aldosterone. The UVIN in ADX rats given no infusion or a low-dose aldosterone infusion was similar in pattern to that of the control group, but the UVIN in the ADX rats given a high-dose aldosterone infusion showed a pattern similar to that of the AHF rats not adrenalectomized. These findings indicate that an increase in plasma aldosterone concentration is an important factor responsible for the decreased diuretic action of furosemide, along with the reduced glomerular filtration rate.
Adrenalectomy↗
Acute diuretic, natriuretic and hypotensive effects of a continuous perfusion of aqueous extract of Urtica dioica in the rat.
This study was performed on anaesthetized male Wistar rats that received a continuous intravenous perfusion during 1.25 h of an aqueous extract of aerial parts of Urtica dioica L. (Urticaceae) at a low dose of 4 mg/kg/h or at a high dose of 24 mg/kg/h, or furosemide (control diuretic) at a dose of 2 mg/kg/h. As compared with a control period in each rat, the arterial blood pressure was reduced proportionally to the dose of the perfusion of the plant extract (15 and 38%, P<0.001, respectively). These effects were accompanied by a correlative increase of diuresis (11 and 84%, P<0. 001, respectively) and natriuresis (28 and 143%, P<0.001, respectively). In the rats perfused by furosemide, the arterial blood pressure was reduced by 28% (P<0.001). The diuresis and natriuresis were also increased proportionally in this case (85 and 155%, P<0.001, respectively). Nevertheless, the hypotensive action of U. dioica was reversible during the recovery periods in about 1 h with the lower dose of the plant extract and furosemide, while the effect of the higher dose was persistent, indicating a possible toxic effect. In conclusion, the results demonstrate an acute hypotensive action of U. dioica that indicates a direct effect on the cardiovascular system. Moreover, diuretic and natriuretic effects were also observed, suggesting an action on the renal function. Finally, the plant extract seems to have a toxic effect at the higher dose.
Analysis of Variance↗
Relationship of urinary kallikrein excretion to urinary potassium excretion during furosemide administration with and without amiloride.
The relationship of urinary kallikrein excretion to urine volume, and to urinary sodium and potassium excretions was studied in normal rats during furosemide diuresis and superimposed injection of amiloride, a K+-sparing diuretic. Continuous infusion of furosemide increased urinary kallikrein, sodium and potassium excretions and the urine volume. Amiloride injection during furosemide diuresis caused further increase in diuresis and natriuresis, but a prompt decrease in urinary kallikrein excretion to basal level, and potassium excretion to below the basal level. The significant correlation of urinary kallikrein excretion to urinary potassium excretion, but not to urine volume and urinary sodium excretion after amiloride injection suggests that the major determinant of urinary kallikrein excretion is renal potassium secretion through a mechanism that is affected by amiloride.
Amiloride↗
Influence of prehydration on the changes in renal tissue composition induced by water diuresis in the rat.
1. The composition of renal tissue was determined in rats before and immediately after intravenous infusion of dextrose (2.5 g/100 ml.) in amounts sufficient to administer a positive fluid load of 4% body weight over 2 hr. The rats were classified into three groups, according to the preinfusion urine osmolality: hydropaenia, normal and moderately diuretic (over 2400, 800-1500 and below 800 mu-osmoles/g H(2)O, respectively).2. In non-infused rats, the steepness of the corticomedullary osmolal gradient varied, due to differences in both water and solute (sodium and urea) contents, and was related to urinary osmolality. Whereas differences in medullary and papillary solute contents occurred between all three groups, papillary water content was significantly higher only in the moderately diuretic animals.3. Dextrose infusion caused the induction of water diuresis, the lowest urinary osmolalities being produced in the previously moderately diuretic animals.4. Dextrose infusion caused a considerable reduction in the steepness of the corticomedullary osmolal gradient in all rats, particularly in the previously hydropaenic animals, due to changes in both solute (sodium and urea) and water contents. Whereas reductions in medullary and papillary solute contents occurred in all three groups, there was no further increase in papillary water content from the already high values seen in the noninfused diuretic animals.5. Thus, dextrose infusion largely abolished any previous differences in tissue water content, whereas significant, though small, differences in osmolal (particularly urea) content persisted.6. These data are discussed in terms of changes and differences in endogenous antidiuretic hormone (A.D.H.) release.7. Changes in the magnitude and direction of the urinary-papillary urea concentration difference are discussed in terms of passive transport, with probable A.D.H.-induced changes in nephron urea permeability.
Animals↗
Effects of Helichrysum ceres extracts on renal function and blood pressure in the rat.
OBJECTIVE: To evaluate the effects of Helicrysum ceres root and leaf extracts on mean arterial blood pressure and renal fluid and electrolyte handling in anesthetized male Sprague-Dawley rats. DESIGN: Cross sectional study. SETTING: Departments of Physiology and Pharmacy, University of Zimbabwe. SUBJECTS: Eight separate groups comprising of control and treated Male Sprague-Dawley rats (n =6 in each group) were anesthetized and placed on a continuous jugular infusion of 0.077 M NaCl at 150 microL min(-1). The left carotid artery was cannulated with polythene tubing and then connected to a pressure transducer for blood pressure measurements. After 3 h equilibration period, consecutive 20 min urine collections and blood pressure measurements were made over the subsequent 4 h of 1 h 20 min control, 1 h treatment and I h 40 min post-equilibration periods for measurements of urine flow and Na+ and K+ excretion rates. Helichrysum ceres leaf extracts at 0.3, 0.6 and 1.2 microg min(-1) roots 0.3, 3 and 6 microg min(-1) were added to the infusate during the treatment period. To establish whether the extracts had activities comparable to drugs already in use, a separate group of animals was administered furosemide (0.12 microg min(-1)) during the treatment period. MAIN OUTCOME MEASURES: Hypotension, Natriuresis and Diuresis. RESULTS: Infusion of graded doses of aqueous leaf extracts of Helicrysum ceres provoked an increase in urine flow rates but did not achieve statistical significance. However, the extracts produced dose dependent decrease in potassium excretion as well as increases in urinary Na+ outputs and diuresis. Administration of the various doses of aqueous root extracts of Helicrysum ceres significantly increased urine flow rate and urinary Na+ excretion in all groups. The intravenous (i.v.) administration of the aqueous root or leaf extracts of Helichrysum ceres significantly depressed mean arterial blood pressure (MAP). The diuretic and natriuretic effects of plant extracts were not significantly different to that of furosemide. CONCLUSION: The results suggest that oral administration to rats of aqueous crude Helicrysum ceres root or leaves extracts induce hypotension and natriuresis.
Animals↗
Diuretic and antinatriuretic responses produced by the endogenous opioid-like peptide, nociceptin (orphanin FQ).
Nociceptin (orphanin FQ) is a novel peptide isolated from brain tissue that has an amino acid sequence most similar to that of the endogenous opioid peptide dynorphin A. Aside from this similarity, the association of nociceptin to the endogenous opioid peptide systems and the functional importance of this new peptide in vivo are not completely known. Here we report that nociceptin is physiologically active in vivo and produces marked changes in the renal excretion of water and sodium. In conscious Sprague-Dawley rats, intravenous infusion of nociceptin produced a profound increase in urine flow rate and decrease in urinary sodium excretion. In further studies, intracerebroventricular (i.c.v.) injection of nociceptin into conscious rats produced a concurrent diuresis (dose-dependent) and antinatriuresis. The magnitude and pattern of the central nociceptin-induced water diuresis was similar to that produced by i.c.v. dynorphin A. Whereas i.c.v. pretreatment with the selective kappa-opioid receptor antagonist, nor-binaltorphimine, completely prevented the renal responses produced by dynorphin A, this antagonist did not alter the diuresis or antinatriuresis produced by central nociceptin. Thus, these results indicate that in conscious rats, nociceptin produces a selective water diuresis via a central nervous system mechanism independent of kappa-opioid receptors. Together, these observations suggest that endogenous nociceptin may be a novel peptide involved in the central control of water balance and ultimately in the regulation of arterial blood pressure. In the future, analogues of nociceptin may prove to be the first clinically useful water diuretics for patients with water-retaining diseases.
Animals↗
A comparison of combinations of diuretics in nephrotic edema.
The metolazone-furosemide combination of diuretics was compared with the thiazide-furosemide combination in nephrotic patients with edema. Nine patients underwent a crossover, randomized study receiving furosemide (2 mg/kg per dose) and either metolazone (dose varied according to weight) or chlorothiazide (10 mg/kg per dose). An additive natriuretic and diuretic effect was observed after both metolazone and thiazide were combined with furosemide. The use of both types of diuretic combination was associated with marked kaliuresis. These combinations of diuretics seem equally effective in inducing natriuresis and diuresis in edematous nephrotic patients.
Administration, Oral↗
Renal effects of bumetanide.
Effects of bumetanide (2.5, 25 and 250 microgram/kg i.v.) on renal hemodynamics and function were investigated in anesthetized dogs using clearance methods, stop-flow analysis and radioactive microsphere. Under conditions of mild isotonic saline loading, significant diuresis was observed within 5 min after the injection of 25 and 250 microgram/kg of the drug, and with the higher dose, a maximal fractional sodium excretion of 34% was observed. The dose of 250 microgram/kg of bumetanide caused a significant 44% increase in blood flow 5 min after the injection. In a hydropenic condition, the reabsorption of free water was significantly reduced, thus suggesting an inhibitory effect on the ascending limb of Henle's loop. In stop-flow experiments, inhibition of sodium reabsorption at the distal tubule was evident. Bumetanide increased blood flow in the juxtamedullary more so than in the superficial area. The increased blood flow in the juxtamedullary area also may contribute to the diuretic action of bumetanide through enhancement of the countercurrent exchange system in the renal medulla.
Absorption↗