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 91 records · Page 5Linked to original sources
PubMed1988

Effects of ethacrynic acid and cystamine on sodium nitroprusside-induced relaxation, cyclic GMP levels and guanylate cyclase activity in rat aorta.

1. Ethacrynic acid, an agent that alkylates sulfhydryl residues, inhibited sodium nitroprusside- and 8-bromo cyclic GMP-induced relaxations. 2. Sodium nitroprusside-induced increased levels of cyclic GMP were unaltered by ethacrynic acid. 3. Concentrations of ethacrynic acid that inhibited sodium nitroprusside-induced relaxation did not affect sodium nitroprusside-activation of crude soluble and particulate fractions of guanylate cyclase, while a higher concentration of ethacrynic acid did inhibit the activation. 4. Cystamine, an agent that oxidizes sulfhydryl residues, inhibited sodium nitroprusside-activation of crude soluble and particulate fractions of guanylate cyclase. Exposure of intact rat aorta to cystamine inhibited basal guanylate cyclase activity in the particulate fraction but, in general, not in the soluble fraction. 5. These results are consistent with the hypothesis that vascular smooth muscle relaxation requires sulfhydryl groups. The sulfhydryl groups that presumably are alkylated by ethacrynic acid are not contained within guanylate cyclase and are involved at a regulatory step after the formation of cyclic GMP. The sulfhydryl groups altered by cystamine may be located on particulate guanylate cyclase and a role for particulate guanylate cyclase in nitrovasodilator-induced relaxation needs to be examined further.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1978

Effects of ethacrynic acid on ion transport and energy metabolism in slices of avian salt gland and of mammalian liver and kidney cortex.

Ethacrynic acid greatly inhibited net transport of ions and aerobic, energy-conserving metabolism in slices of avian salt gland, rat liver, and rat and guinea-pig kidney cortex. The effects of increasing concentrations of ethacrynic acid on the transport of Na+, K+ and Cl- ran closely parallel to its effects on tissue ATP levels and respiration. The concentration needed for maximal inhibition of transport reduced ATP levels by 80--90%. Respiration was reduced by 80--90% in salt gland and kidney cortex, and by a maximum of 30% in liver slices. The effects of low concentrations of ethacrynic acid required time to become fully manifest in some tissues, and the development of transport inhibition followed a similar course to decline of respiration and ATP levels. Ca2+ extrusion by liver cells was inhibited by ethacrynic acid. The concentration dependence of the inhibition was similar to that shown by the other transport systems inhibited. There was no distinction evident between the sensitivity of Na+ extrusion and of K+ accumulation to the diuretic. Lactate production increased as respiration decreased in the presence of increasing concentrations of ethacrynic acid. We conclude that ethacrynic acid acted primarily as an inhibitor of mitochondrial respiration and ATP synthesis in the tissue slices, and that inhibition of ion transport was a nonspecific consequence of the failure of the energy supply.

Adenine Nucleotides↗
PubMed1992

The effect of intracamerally injected ethacrynic acid on intraocular pressure in patients with glaucoma.

We studied the effect of ethacrynic acid on intraocular pressure in eyes with advanced open-angle glaucoma. Five to 15 microliters of ethacrynic acid (3.3 to 9.8 micrograms) was injected intracamerally after retrobulbar anesthesia was achieved in five eyes of five patients with advanced glaucoma. Intraocular pressure before treatment ranged from 26 to 46 mm Hg with maximal medical treatment. A reduction in intraocular pressure from 9 to 31 mm Hg was observed in all patients three to 24 hours after treatment, and this effect lasted for three days, with a gradual return of intraocular pressure to pretreatment values one week after treatment. No acute corneal or anterior chamber side effects were observed and results of corneal endothelial cells counts were essentially unchanged two months after treatment. We suggest that ethacrynic acid may represent a new class of antiglaucoma medication. Intracameral administration of ethacrynic acid or a derivative might be contemplated in the future at the time of other ocular surgical procedures to treat short-term intraocular pressure increase.

Adult↗
PubMed1975

[Haemodynamic effects of furosemide and ethacrynic acid (author's transl)].

The haemodynamic effects of intravenous injections of furosemide and ethacrynic acid were studied in 12 patients during rest and exercise. Cardiac output, heart rate and arterial blood pressure showed no significant changes after injection of furosemide or ethacrynic acid. Few minutes after injection of furosemide there were significant falls of pulmonary artery diastolic pressure and right atrial pressure, whereas no changes were seen after injection of ethacrynic acid. This initial effect of furosemide apparently is of primarily vascular origin, causing an increased peripheral venous capacitance. Ethacrynic acid failed to exhibit any direct vascular effect.

Acute Disease↗
PubMed1976

[Demonstration of the inhibitory effect of ethacrynic acid on permeability to chlorine].

Ethacrynic acid specifically inhibits chloride permeability in Ox erythrocyte. The I50 is 7 x 10(-6) M. The inhibitory effect is instantaneous and completely reversed by washing the cells with a Ringer solution. Dihydroethacrynic acid, a derivative that lacks the ability to combine with SH groups, also inhibits chloride permeability and the characteristics of inhibition are strictly identical. It is a proof that ethacrytic acid does not act by its reactivity with thiol groups.

Animals↗
PubMed1982

[Role of SH-groups in the pharmacology of the action of novurite and ethacrynic acid].

In experiments in vivo the mercuric diuretic, novurite, and ethacrynic acid in therapeutic doses (25 and 50 mg/kg, respectively) do not block the respiration and active transport of calcium in the kidney mitochondria. The diuretic effect of these substances is not prevented by cystein (50 mg/kg), the donator of sulphydryl groups. In vitro novurite (3 mM) and ethacrynic acid (1 mM) block the systems of ionic transport inthe kidney epithelium cells and in concentrations of 0.2 and 0.5 mM, respectively, disturb the oxygen uptake and oxidative phosphorylation in the kidney mitochondria. A preliminary administration of cystein (5 mM) into the incubation medium prevents these effects. Novurite and ethacrynic acid manifest the typical thyol toxins of general cell effect in doses considerably exceeding the therapeutic ones. A specific "kidneys" effect of these substances is not connected with their ability to block SH-group of biologically active substances.

Alkylmercury Compounds↗
PubMed1985

Inhibitory effects of gentamicin and ethacrynic acid on mammalian microsomal protein synthesis.

The ototoxic antibiotic gentamicin, and the ototoxic diuretic ethacrynic acid, both produce inhibitory effects on protein synthesis in microsomes isolated from rat brain. Inhibitory effects appear to be essentially independent of each other. The inhibitory dose-response curve for gentamicin is logarithmic, while that for ethacrynic acid is linear. The dose-response curves make gentamicin the predominant inhibitor when the drugs are combined at low concentrations and ethacrynic acid the predominant inhibitor when the drugs are combined at high concentrations. Accumulation of aminoglycoside by tissues of the inner ear may result in inhibition of protein synthesis in spite of low and transient plasma levels of the drug. Further inhibition of translation by ethacrynic acid could account, in part, for the ototoxic interaction of aminoglycosides and high ceiling diuretics.

Animals↗
PubMedDate not supplied

Ultrastructure in the stria vascularis of the guinea pig following intraperitoneal injection of ethacrynic acid.

Following intraperitoneal injection of ethacrynic acid, progressive, mainly reversible changes occurred in the stria vascularis, affecting all three cell types and the capillary basal laminae. Both marginal and intermediate cells showed abnormalities early, at a time when EP was just beginning to decline. Progressive changes in marginal cells culminated in apical bulging followed by recession of the swelling and stretching of the cells concomitant with gross interstitial oedema. Marginal cell mitochondria showed damage and the transcellular tubule system was dilated. Intermediate cells also showed a progression of changes, culminating in a marked, but reversible, shrinkage. The time of appearance of severe strial derangement correlated with the time of maximal depression of EP. The ability of the stria to regain rapidly an almost normal morphology appeared to be due partly to the distribution and orientation of microtubules in marginal and intermediate cells preventing major disruption of stria vascularis architecture.

Animals↗
PubMed1975

Interaction of ethacrynic acid with control sites of renal glucose metabolism.

Ethacrynic acid stimulates in vitro concentration dependent renal gluconeogenesis from substrates which enter the gluconeogenic pathway at the level of the triosephosphates like glycerol or fructose or from substrates which have to pass the oxaloacetate shuttle like pyruvate or from intermediary products of fatty acid oxydation or citrate cycle. Our results suggest that a site of action of ethacrynic acid in this metabolic aspect is the enzyme system fructose diphosphatase/frutose-6-phosphate kinase and eventually additionally pyruvate carboxylase.

Acetoacetates↗
PubMed1995

Effect of frusemide, ethacrynic acid and indanyloxyacetic acid on spontaneous Ca-activated currents in rabbit portal vein smooth muscle cells.

1. The effect of frusemide, ethacrynic acid and indanyloxyacetic acid was investigated on spontaneous calcium-activated chloride (ICl(Ca)) and potassium currents (IK(Ca)) in rabbit portal vein cells with the perforated patch technique. 2. Frusemide (0.3-1.0 x 10(-3) M) reduced the amplitude of spontaneous transient inward chloride currents (STICs) in a concentration-dependent manner. The degree of inhibition on STIC amplitude was similar between -50 and +30 mV and frusemide did not alter the STIC reversal potential (Erev). 3. The voltage-dependent exponential decay of STICs, which is thought to represent closure of chloride channels, was not altered by frusemide. 4. The amplitude and frequency of spontaneous potassium outward currents (STOCs) were not altered by frusemide. Since both STICs and STOCs are activated by calcium released from intracellular stores these data indicate that frusemide may block directly ICl(Ca). 5. Ethacrynic acid (2-5 x 10(-4) M) decreased the amplitude of STICs in a concentration-dependent manner by a similar amount at potentials of -50 to +30 mV but did not alter the STIC Erev. However, these concentrations of ethacrynic acid also reduced STOC amplitude and 5 x 10(-4) M ethacrynic acid evoked a sustained outward current in most cells at 0 mV; thus ethacrynic acid has a more complex action than simple block of ICl(Ca). 6. Indanyloxyacetic acid reduced both STIC amplitude and decay time without affecting STOCs and thus also seems to inhibit directly ICl(Ca). It is discussed whether block of ICl(Ca) mediates the vasodilator effect of these agents.

Animals↗
PubMed2001

Rat liver microsomal lipid peroxidation produced during the oxidative metabolism of ethacrynic acid.

Thiobarbituric acid reactive substances (TBARS) were produced in rat liver microsomal suspension incubated with ethacrynic acid (loop diuretic drug) and NADPH. Two oxidative metabolites of ethacrynic acid with dicarboxylic acid and hydroxylated ethyl group, respectively, were formed in the reaction mixture. The oxidative metabolism of ethacrynic acid was inhibited by cytochrome P450 inhibitors. The formation of TBARS was remarkably depressed by inhibitors like diethyldithiocarbamate and disulfiram. These results indicate that lipid peroxidation occurred in rat liver microsomes through the oxidative metabolism of ethacrynic acid.

Animals↗
PubMed1977

Antagonism of non-steroidal anti-inflammatory drugs and narcotic analgesics against ethacrynic acid induced writhing.

Thiol-group reactive agents [alloxan, N-ethyimaleimide (NEM), ethacrynic acid, p-chlormercuribenzoate (PCMB)] were shown to induce a writhing syndrome in mice and rats when injected i.p. in appropriate dosage. Non-steroidal anti-inflammatory agents, narcotic analgesics and also psychotropic drugs inhibit the syndrome elicited in rats by ethacrynic acid. Rats pretreated with cysteine i.p. show a greatly reduced nociceptive response to ethacrynic acid or alloxan.

Analgesics↗
PubMed1976

Ethacrynic acid induced release of prostaglandin E to increase renal blood flow.

Ethacrynic acid administered to anesthetized dogs was found to increase the level of prostaglandin E as determined by radioimmunoassay in renal venous blood at the time when renal blood flow was increased by this agent. No change was found in the renal venous level of prostaglandin F. When ethacrynic acid was administered after treatment with indomethacin, which blocks the increase in renal blood flow induced by the natriuretic agent, no increase in the renal venous level of prostaglandin E was seen. Thus, the dilation of the renal vasculature would appear to be caused by a stimulation of synthesis and release of prostaglandin E by ethacrynic acid.

Animals↗
PubMed1987

The influence of the ammonium ion on the stability of ethacrynic acid in aqueous solution.

Investigations by reversed-phase HPLC into the stability of ethacrynic acid in buffered aqueous solutions containing either sodium or ammonium ions showed that the extent of degradation was influenced both by the species and concentration of the cation. A reported incompatibility between ethacrynic acid and the ammonium ion, attributed to the influence of the ammonium ion on an equilibrium existing between ethacrynic acid and one of its known degradation products, was shown to be due to the generation of an additional degradation product in ammonium-containing solutions only. This product was isolated and identified. Different pathways of degradation were shown to be operative in sodium- and ammonium-containing solutions. The addition of formaldehyde or a formaldehyde scavenger (hydroxyammonium chloride) was found to influence the rate of loss of ethacrynic acid, but the decomposition products provided no evidence for the existence of the reported equilibrium.

Journal Article↗
PubMed1979

The nature of the negative endocochlear potentials produced by anoxia and ethacrynic acid in the rat and guinea-pig.

1. The alterations in the Na+ and K+ concentrations of the cochlear endolymph and in the endocochlear potential were followed simultaneously by means of ion-sensitive and conventional micro-electrodes during simple anoxia, during anoxia after i.v. ethacrynic acid and after i.v. ethacrynic acid alone. The endolymphatic pH changes were measured separately and the effect of perilymphatic ethacrynic acid upon the endocochlear potential was investigated. 2. The over-all Na+:K+ permeability ratio for the endolymph system was determined in individual animals for the first time using an indirect method. The normal mean values of 0.27 (rat) and 0.38 (guinea-pig) were increased after ethacrynic acid. Permeability changes occurred during anoxia but were delayed in onset. 3. The negative endocochlear potentials in each situation behaved quantitatively like modified K+ diffusion potentials largely dependent upon the K+ and Na+ gradients between endolymph and perilymph.

Animals↗
PubMed1996

Effects of chronic ethacrynic acid exposure on glutathione conjugation and MRP expression in human colon tumor cells.

Chronic exposure to ethacrynic acid of a subcloned HT29 human colon cancer cell line produces a 3- to 4-fold increase in the level of resistance to this agent. The resistant cells (HT6-8) have an enhanced capacity to metabolize the parent drug and efflux it from the cell. This is reflected in a 5-fold enhanced decompositioning rate constant for ethacrynic acid in HT6-8 (3.47 x 10-3 min-1) versus wild type cells (1.58 x 10-2 min-1). We observed that the glutathione conjugate of ethacrynic acid is an effective competitive inhibitor for binding to the multidrug resistance-associated protein by [35S]azidophenacyl-glutathione, a photoaffinity analog of glutathione. In addition, the HT6-8 cells overexpressed multidrug resistance-associated transcript 2- to 3-fold. These results suggest that resistance to ethacrynic acid results from a concerted, coordinate increase in defense mechanisms which detoxify the drug and remove its conjugate via plasma membrane efflux.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Effects of frusemide, ethacrynic acid and chlorothiazide on the portal vein of normotensive and spontaneously hypertensive rats.

The effects of frusemide, ethacrynic acid and chlorothiazide were studied in the Wistar Kyoto (WKY) rats and spontaneously hypertensive rat (SHR) portal veins in vitro. Frusemide produced concentration-dependent contractions of the portal vein from both WKY control and SHR. The WKY were more sensitive (as judged by the EC50) whilst a greater maximal response was generated in the SHR. The contractile response to frusemide in WKY rats was attenuated reversibly by phenoxybenzamine whereas the latter was ineffective in the SHR. Ethacrynic acid produced reductions of the myogenic rhythmic contractions of the portal vein in a concentration-related manner in both WKY and SHR. The inhibitory action of ethacrynic acid was greater in the SHR than in the WKY control rats. The inhibitory action of ethacrynic acid was blocked by propranolol suggesting the involvement of beta adrenoceptors. Chlorothiazide, on its own, had no observable effect on the portal vein. However, it reduced the sensitivity of the vein to noradrenaline and K+. This reduction was greater in the SHR than in the WKY. It is concluded that some of the observed effects of these diuretics may contribute beneficially to their anti-hypertensive actions.

Animals↗