Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ETHACRYNIC ACID”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 1,243 records · Page 69Linked to original sources
PubMed2003

Changes in cell proliferation in rat and guinea pig cochlea after aminoglycoside-induced damage.

Cell proliferation in the cochleae of guinea pigs and rats was investigated after systemic application of kanamycin sulfate (KM) and ethacrynic acid (EA). Bromodeoxyuridine (BrdU) was injected daily for 10 days, after which the number of BrdU-positive cells was counted in paraffin sections of the cochlea. Only a few BrdU-positive cells were present in the spiral ligament and among the acoustic nerve fibers in the non-deafened control animals. Animals treated with KM and EA had profound hearing loss and significant increases in the number of BrdU-positive cells in the spiral ligament and among the acoustic nerve fibers. No BrdU-positive cells were found in the auditory sensory epithelium of any animal. These findings suggest that in the mature mammalian cochlea cell proliferation increases in nonsensory regions after ototoxic damage but may not occur in the auditory sensory epithelium.

Aminoglycosides↗
PubMed1986

Diuretic use in critical care.

Diuretics have found wide application in critical care medicine. The use of mannitol and loop diuretics in a variety of life-threatening disorders is reviewed. The combined venodilatory and natriuretic effects of bumetanide, furosemide and ethacrynic acid relieve congestive symptoms in pulmonary edema. Although commonly administered to prevent development of acute tubular necrosis or in varying stages of evolving disease, few data are available to demonstrate the efficacy of mannitol or loop diuretics. An approach to the oliguric patient with acute tubular necrosis is described. The dangers of hyponatremia are reviewed, and the rational use of loop diuretics and hypertonic saline is outlined. The 3 loop-active agents inhibit calcium reabsorption in the thick ascending limb of Henle's loop and therefore have proved useful in treating hypercalcemia. A practical approach to the diuretic-saline treatment of severe hypercalcemia is outlined. The kaliuretic effect of loop diuretics can be used to advantage in patients with acute or chronic hyperkalemia. A guide to such therapy is described.

Biological Transport↗
PubMed1987

Nutritional status, glutathione levels, and ototoxicity of loop diuretics and aminoglycoside antibiotics.

Chinchillas deprived of food for 48 h prior to the administration of a combined dose of ethacrynic acid (10 mg/kg) and kanamycin (100 mg/kg) suffered a profound hearing loss. Fed animals did not demonstrate any hearing loss at the same dose levels. Drug metabolism may be the common pathway by which ototoxic agents interact, by a mechanism which is common to both the cochlea and the kidney. Glutathione (GSH) is a tripeptide which is involved in several pathways in the detoxification of active oxygen and reactive species formed during xenobiotic metabolism. The enhanced auditory dysfunction was paralleled by one-third decline in hepatic glutathione levels in the food-deprived animals. Manipulation of endogenous GSH levels may mitigate the toxicities of many of these drugs, which otherwise limit their clinical usefulness. These results also indicate that nutritional status may have important clinical implications during drug therapy.

Animals↗
PubMed1984

Evidence for bicarbonate-dependent lithium reabsorption in dog kidneys.

To examine whether lithium is reabsorbed along a transcellular or a paracellular route, experiments were performed in anesthetized volume-expanded dogs under conditions of constant glomerular filtration rate (GFR). Quabain, in doses inhibiting about 80% of Na, K-ATPase, and ethacrynic acid, another inhibitor of transcellular NaCl reabsorption, did not inhibit lithium or bicarbonate reabsorption. Lithium reabsorption increased in proportion to plasma concentration of lithium (PLi) up to 12 mM, suggesting a passive transport of lithium. During ouabain administration acetazolamide halved bicarbonate reabsorption, the main driving force for paracellular reabsorption, and halved the reabsorption of lithium. The reabsorbate concentration of lithium, calculated from data obtained before and after acetazolamide infusion, was almost equal to PLi. Mannitol, which reduces paracellular osmotic transport without affecting bicarbonate reabsorption, reduced lithium and chloride reabsorption in the same proportion as acetazolamide (r = 0.87). Combined acetazolamide and mannitol administration reduced fractional lithium reabsorption to 0.09 +/- 0.02. These data indicate that lithium is not actively transported but reabsorbed passively along a paracellular route by osmotic forces provided by transcellular NaHCO3 reabsorption.

Acetazolamide↗
PubMed1971

Formation of saliva and potassium transport in the perfused cat submandibular gland.

1. In the cat submandibular gland perfused with modified Locke solutions, salivary secretion during acetylcholine (ACh) infusion and K uptake from the perfusion fluid after the ACh-induced K loss were measured.2. Strophanthin G (10(-5)M) abolished K uptake, whereas salivary secretion was unaffected.3. Ethacrynic acid (10(-4)-2 x 10(-4)M) hardly affected K uptake whereas salivary secretion was severely inhibited.4. During perfusion with Ca-free solution K uptake was unaffected, whereas salivary secretion was severely reduced.5. The presence or absence of CO(2)/HCO(3) in the perfusion fluid was of no importance for the secretory process and the K uptake. Acetazolamide (2 x 10(-4)-10(-3)M) did not inhibit these transport processes.6. It is suggested that two kinds of Na transport occur in the acinar cells of the salivary glands: a Na extrusion coupled with K uptake, responsible for the maintenance of the concentration gradients across the cell membrane; and a Na transport coupled with Cl transport into the acinar lumen, responsible for the formation of the primary secretion.

Acetazolamide↗
PubMed1984

Noise-induced hearing loss as influenced by other agents and by some physical characteristics of the individual.

The interaction of noise with a variety of other agents and with some physical characteristics of the individual to produce noise-induced hearing loss is reviewed critically. The review is restricted, for the most part, to publications since 1970. Other agents interacting with steady-state noise that are reviewed here include: (1) ototoxic drugs (kanamycin, neomycin, ethacrynic acid, furosemide, and salicylates), (2) impulse noise, and (3) whole-body vibration. Physical characteristics of the individual that are reviewed are: (1) age, (2) presence of previous hearing loss from prior noise exposure, (3) eye color, and (4) race. Suggestions for future research in this general area are also made. Some of these suggestions are as follows: (1) to extend studies of the interaction of steady-state noise with impulse noise, salicylates, and whole-body vibration to encompass a broader range of exposure conditions, including exposure conditions typically encountered by the worker, (2) to develop an animal model of presbycusis to explore the interactions of noise-induced hearing loss and presbycusis, and (3) to explore the potential interactions resulting from concurrent exposure to multiple agents, such as impulse noise and ototoxic drugs, in younger, more susceptible animals.

Acoustic Stimulation↗
PubMed1977

Natriuretic and phosphaturic response to diuretics after parathyroidectomy in dogs.

Intact and acutely parathyroidectomized (TPTX) dogs were studied during hydropenia, volume expansion (VE), volume expansion plus ethacrynic acid (EA), and volume expansion plus acetazolamide (AZ). In intact dogs, VE produced marked increases in both Na+ and phosphate (Pi) excretion; in TPTX dogs, Na+ excretion increased but phosphaturia was minimal. Addition of EA increased Na+ but not Pi excretion in both groups. Discontinuing EA and substituting AZ in intact dogs produced a marked increase in Pi excretion compared to both VE and VE + EA. In TPTX dogs, AZ failed to increase Pi excretion compared to VE alone. The results suggest that increased distal Pi absorption in acutely TPTX dogs is not associated with NaCl reabsorption in the thick ascending loop of Henle or may occur at an alternative nephron site. Furthermore, the increased distal Pi reabsorptive capacity revealed by TPTX can overcome the increased distal Pi delivery produced by the superimposition of AZ on VE.

Acetazolamide↗
PubMed1997

Determination of dissociation constants of loop diuretics in acetonitrile-water mixtures.

The dissociation pK values of the representative loop diuretics furosemide, bumetanide and ethacrynic acid in 10, 30, 40, 50 and 70% (w/w) acetonitrile-water mixtures at 298.15 K were determined, according to the rules and procedures endorsed by IUPAC. The variation in pK values over the whole composition range studied can be explained by tacking into account the preferential solvation of ionizable substances in acetonitrile-water mixtures. With a view to determining the pK values of the loop diuretics studied in any of the binary solvent acetonitrile-water mixtures, correlations of pK values and different bulk properties of the solvent were examined, and the linear solvation energy relationships method, LSER, has been applied. The pK values were then correlated with the pi*, alpha and beta solvatochromic parameters of acetonitrile-water mixtures. The resulting equations allowed us to calculate pK values for the loop diuretics in any acetonitrile-water mixture up to 70% (w/w) acetonitrile.

Acetonitriles↗
PubMedDate not supplied

Differential expression of alpha-like glutathione S-transferase (GST) isoforms in catfish intestine.

Previous studies suggested that dietary composition affected glutathione S-transferase (GST) activity in catfish intestine, and this activity varied along the intestine. In this study, catfish were fed a semi-purified diet or a commercial chow for at least 2 weeks. GST activity, percent protein cross-reacting with anti-catfish GST pi antibody, and immuno-cross-reactivity with antibodies specific for human alpha, mu, pi and theta class GSTs were determined in cytosol prepared from sections of proximal, medial, and distal intestine. The bulk of GST activity with 1-chloro-2,4-dinitrobenzene (CDNB) and ethacrynic acid, and the percent protein cross-reacting with anti-catfish GST pi were in the more proximal segments and dropped off distally in the two diet groups. The percent of cross-reacting GST protein in the proximal section of fish fed on commercial chow was significantly higher (4.3 +/- 1.7%) than in fish fed purified diet (2.3 +/- 0.2%). Further Western blot analysis revealed a differential expression of GST isoforms only in the distal segment of fish fed commercial chow that recognized human anti-alpha GST antibody. Distal intestinal segments of catfish exposed to 3,3',4,4'-tetrachlorobiphenyl (TCB) and beta-naphthoflavone (BNF) also revealed expression of distinct alpha-like GST isoforms. Results strongly suggest the distal segment as a site for potential biomarkers for polycyclic aromatic hydrocarbon (PAH)- and co-planar polychlorinated biphenyl (PCB)-type contaminants.

Animals↗
PubMed1973

Spontaneous salivation in the rabbit submandibular gland.

1. Salivation has been studied in the submandibular gland of the rabbit. A very slow spontaneous salivation took place when all possibility of nerve influence had been excluded. Salivation was not due to ultrafiltration.2. The ;spontaneous' saliva had a mean K concentration of 148 mM and Na concentration of 46 mM. With increasing salivation rate produced by parasympathetic nerve stimulation, K concentration fell to a plateau level of about 30 mM whilst Na concentration fell rapidly to reach the low value of 3 mM, then began to rise again at the higher flow rates.3. Ligation of the submandibular duct produced a reversal of the ion concentrations in spontaneous saliva. By 4 days K concentration was lower and that of Na higher than control values until by 2 weeks the effect was maximal with mean concentrations of 25 mM for K and 153 mM for Na.4. Ouabain increased the spontaneous salivation rate and ethacrynic acid slowed or prevented it altogether. On the basis of the known sites of action of these drugs it is postulated that two pumps are involved in the regulation of spontaneous salivation. There appears to be basal activity of an acinar mechanism pumping NaCl into the lumen, taking water with it. This pump is activated directly or indirectly by the intracellular Na concentration which itself is controlled by an Na-K exchange pump.5. Excitation of the sympathetic trunk produced a small, though definite, increase in salivation rate. There was evidence that myoepithelial cells might also be involved in the sympathetic response and that they were activated by alpha receptor stimulation. Salivation evoked by sympathetic nerve stimulation would seem to be a response to beta receptor stimulation, but the possibility that activation of both alpha and beta receptors was required could not be excluded entirely.

Animals↗
PubMed1968

Factors influencing the electrical potential across the mucosa of rat colon.

1. An investigation has been carried out into various factors which influence the transmucosal potential difference (p.d.) of rat colon in vivo when the p.d. is either high (> 30 mV) or low (< 20 mV).2. The p.d. was uninfluenced by short duration anaesthesia with ether or pentobarbitone. When anaesthesia was prolonged for several hours, p.d. rose steadily. The gradient of p.d. along the descending colon which developed and its elimination by adrenalectomy suggested that the rise was due to increased secretion of adrenal steroids.3. P.d. was increased by Na depletion after a delay of about 18 hr and fell again following Na repletion with a similar time delay. A characteristic gradient of p.d. along the descending colon was seen.4. Both haemorrhage and anoxia caused a rapid fall of p.d. P.d. was restored rapidly to its previous level when anoxia was corrected.5. Vasopressin (I.V.) in low dose was without effect; in high dose it caused a transient fall of p.d. associated with intense vasoconstriction of gut blood vessels.6. The following factors studied were without effect on p.d.: presence of glucose within the lumen; considerable osmotic gradients across the mucosa; variation of luminal pH over the range 5.2-9.8; intravenous administration of acetazolamide, chlorothiazide, frusemide, triamterene, ethacrynic acid or ouabain. Ouabain in the luminal solution also had no effect in all but two rats in which a small fall of p.d. was seen.7. 2,4-dinitrophenol, 10(-2)M, in the lumen caused a small fall of p.d. only if the p.d. was high.8. Experiments were done to determine the effect on p.d. of altering the ionic composition of the luminal solution. When the p.d. was low (< 20 mV) alteration of [Na], [K] or [Cl] produced small absolute changes of the p.d., all of comparable magnitude. The changes could be interpreted as due to diffusion potentials resulting from the ionic gradients across the mucosa. When the p.d. was high (> 30 mV), it showed a striking dependence on the luminal [Na] only, consistent with the presence of a large p.d. due to active Na transport.

Acetazolamide↗
PubMed1983

Placental calcium and phosphorus transfer in the guinea pig: lack of effect of modulators of Ca-ATPase and alkaline phosphatase activity.

The effects of modulators of Ca-ATPase and alkaline phosphatase (AP) activity on placental calcium and phosphorus transfer were studied using the in situ perfused guinea pig placenta. The diuretics ethacrynic acid and furosemide had no significant effect on placental calcium and phosphorus transfer when injected into the mother (1.0 or 10.0 mg X kg-1) or added to the solution perfusing the fetal side of the placenta (0.25 or 2.0 mM). These two drugs have previously been shown to inhibit placental Ca-ATPase and enhance AP activity in vitro. D-Penicillamine, which inhibits placental AP but not Ca-ATPase activity in vitro, also had no significant effect on net calcium and phosphorus transfer from mother to fetus either when given to the mother (50 mg X kg-1) or added to the placental perfusion solution (0.25 or 2.0 mM). These results suggest that placental transfer of calcium and phosphorus in the guinea pig may not be directly related to placental Ca-ATPase and AP activities.

Alkaline Phosphatase↗
PubMed2003

Cytosolic and mitochondrial glutathione in microglial cells are differentially affected by oxidative/nitrosative stress.

Glutathione (GSH), the major cellular protectant against reactive oxygen and nitrogen species, is compartmentalized in a cytosolic (c) and a mitochondrial (mt) pool. We investigated how c-GSH and mt-GSH are differentially affected by endogenously produced nitric oxide (NO). Microglial cell line (N9) cultures were immunostimulated with lipopolysaccharide/interferon-gamma to elicit the inducible isoform of NO synthase (iNOS). Despite a significant reduction in total GSH, the mt-GSH remained nearly unaffected by iNOS-mediated NO production. To investigate possible consequences of GSH depletion on the mitochondrial membrane potential, we used buthionine sulfoximine (BSO) to reduce separately the c-GSH, whereas ethacrynic acid (EA) was applied to deplete both mt-GSH and c-GSH. The mitochondrial membrane potential was more vulnerable to NO exposure in EA-pretreated cultures than in BSO-pretreated cultures, indicated by a potentiated release of tetramethylrhodamine from mitochondria into the cytosol. To relate the EA-mediated decrease in mitochondrial membrane potential to the oxidant buildup after GSH depletion, we loaded the cells with the oxidant-sensitive fluorochrome 2',7'-dihydrodichlorofluorescein (DCF) diacetate. EA treatment caused an increase in DCF fluorescence over time that was potentiated when the iNOS expression was stimulated. Inhibition of NO production abolished this effect. We conclude that endogenous NO production in microglial cells does not compromise the mt-GSH pool which, in turn, might explain the ability of these cells to combat high-output NO production.

Buthionine Sulfoximine↗
PubMed1977

Comparison of the effect of two groups of diuretics on renin secretion in the anaesthetized dog.

1. The effects of two groups of diuretics on renin secretion have been compared in dogs anaesthetized with pentobarbital. 2. Frusemide, ethacrynic acid and bumetanide cause an immediate rise in renin secretion which is not inhibited either by DL-propranolol or by a bilateral ureterovenous anastomosis which prevents salt and water loss. 3. Clopamide, metolazone and indapamide do not cause an immediate rise in renin secretion. Renin hypersecretion is induced only 1 h after intravenous injection of these diuretics. 4. Renin secretion was studied for 6 h after frusemide injection: the immediate rise was followed by a later increase in renin secretion. This later rise was inhibited by propranolol and by ureterovenous anastomosis. 5. These results allow us to distinguish between a direct renal mechanism responsible for early renin hypersecretion, which appears to be connected with the action of the diuretic on the ascending limb of Henle's loop, and an indirect mechanism responsible for late renin hypersecretion, which appears to be connected with salt and water loss.

Animals↗
PubMed1977

Effect of dehydration on renal blood flow in dog.

The effect of dehydration on intrarenal blood flow was investigated in 11 dogs, using polarographic determination of H2-gas desaturation for measuring local blood flow in inner cortex (ICF) and outer cortex (OCF). Dehydration was induced by 48 h water deprivation +2-300 mg ethacrynic acid (EA) per os the day before the experiment. Compared to a control group (n=9) ICF was markedly reduced to 2.40 +/- 0.47 ml/min X g (control 3.23 +/- 0.64) whereas OCF 3.29 +/- 0.80 ml/min X g was nearly unchanged (control 3.59 +/- 0.85). The ratio OCF/ICF was increased to 1.37 (1.11). Further dehydration by hypertonic peritoneal dialysis for 3 h increased Hct to 60 +/- 4 and further reduced OCF and ICF, without significant change of the OCF/ICF-ratio. At Hct above 55 sudden and intermittent changes in local cortical blood flow were recorded randomly at individual electrode sites, showing ischemic periods lasting for 1 to 60 min. Such flow changes were observed in 13 of 14 expts. and were not accompanied by changes in RBF. It is concluded that moderate dehydration causes a greater reduction of ICF than of OCF. Severe dehydration gives in addition rise to patchy, intermittent ischemia in both cortical layers.

Animals↗
PubMed1980

Diuretics stimulate H+ secretion in turtle urinary bladder.

The effect of various diuretics on H+ secretion was studied in the isolated short-circuited urinary bladder of the turtle. Mucosal (urinary) chlorothiazide stimulated H+ secretion promptly, from 1.33 +/- 0.24 to 3.03 +/- 0.25 mueq/h (P less than 0.001). The effect was rapidly reversible upon washout of the drug, H+ returning to control levels, 1.37 +/- 0.26 mueq/h (P less than 0.001). Similar effects were observed with mucosal hydrochlorothiazide and mucosal ethacrynic acid/cysteine. Stimulation of H+ secretion occurred in the presence or the absence of exogenous CO2, in the presence or absence of mucosal Na+ and during inhibition of Na+ transport by ouabain. There was no stimulation of H+ secretion by uncomplexed ethacrynic acid or by mucosal furosemide. The nondiuretic sulfonamide, sulfasoxizole, and the nonsulfonamide buffer, borate, had no effect on H+ SECRETION. These observations indicate that the stimulatory effect of diuretics on H+ secretion is not related to active sodium transport, transepithelial electrical potential, or the buffering capacity of the drugs. Since the transepithelial pH gradient at which active H+ secretion was abolished was identical for chlorothiazide-treated tissues (2.68 pH U) as for control tissues (2.65 pH U, NS), the data suggest that the protonmotive force of the H+ pump was unaffected by the diuretic. This observation, plus the rapid onset and reversibility of the drugs, is consistent with an effect on the mucosal membrane to increase H+ conductance (K). The findings raise the possibility that direct enhancement of renal H+ secretion may play a role in the metabolic alkalosis induced by some diuretics.

Animals↗
PubMed1986

The effect of loop diuretics on the vestibular system. Assessment by recording the vestibular evoked response.

Whether or to what extent loop diuretics, e.g., ethacrynic acid and furosemide, affect the vestibular system is controversial. We studied this problem by recording in cats the short-latency vestibular evoked response (VsER) to acceleration stimuli by skin electrodes before and after local or systemic administration of loop diuretics. The effect on the VsER was minimal in contrast to the major changes that appeared in the auditory evoked response, in which, among the waves known to originate from the brain stem, the most affected was N1. These findings suggest that the vestibular end-organ function is minimally affected by loop diuretics and that the changes in the vestibulo-ocular reflex reported by several authors might be due to the effect of the drugs on the central nervous system. Thus, recording of the VsER in experimental animal models might serve as a useful tool for direct evaluation of the effect of certain drugs and conditions on the vestibular system.

Animals↗
PubMed1975

Renal sodium reabsorption during saline loading and distal blockade in newborn dogs.

The ability of the proximal tubule to respond to saline expansion and varying filtered sodium loads was studied in 27 neonatal dogs aged 1-23 days. Sodium reabsorption beyond the proximal tubule was blocked with ethacrynic acid and chlorothiazide. When puppies received an intravenous load of 0.9% saline for 1.5 h, fractional sodium reabsorption averaged 0.985. After the addition of distal blockade to the saline infusion fractional Na reabsorption fell to 0.512. During distal blockade alone fractional Na reabsorption was 0.701, and after 1.5 h of saline expansion added to distal blockade fractional Na reabsorption fell to 0.493. Thus, there was a significant decrease in proximal tubular fractional Na reabsorption after saline expansion in neonatal dogs, and the high fractional Na reabsorption and low Na excretion during saline loading without distal blockade must be due to a large distal Na reabsorption. When filtered sodium load was varied by raising and lowering the glomerular filtration rate during distal blockade, there was excellent correlation between amount of filtered and reabsorbed sodium (r = 0.92). Thus, glomerulotubular balance exists in newborn dogs when there is no saline expansion.

Age Factors↗