Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “CHLOROTHIAZIDE”

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 865 records · Page 48Linked to original sources
PubMed2003

Membrane potential stabilization in amphibian skeletal muscle fibres in hypertonic solutions.

This study investigated membrane transport mechanisms influencing relative changes in cell volume (V) and resting membrane potential (E(m)) following osmotic challenge in amphibian skeletal muscle fibres. It demonstrated a stabilization of E(m) despite cell shrinkage, which was attributable to elevation of intracellular [Cl(-)] above electrochemical equilibrium through Na(+)-Cl(-) and Na(+)-K(+)-2Cl(-) cotransporter action following exposures to extracellular hypertonicity. Fibre volumes (V) determined by confocal microscope x z - scanning of cutaneous pectoris muscle fibres varied linearly with [1/extracellular osmolarity], showing insignificant volume corrections, in fibres studied in Cl(-)-free, normal and Na(+)-free Ringer solutions and in the presence of bumetanide, chlorothiazide and ouabain. The observed volume changes following increases in extracellular tonicity were compared with microelectrode measurements of steady-state resting potentials (E(m)). Fibres in isotonic Cl(-)-free, normal and Na(+)-free Ringer solutions showed similar E(m) values consistent with previously reported permeability ratios P(Na)/P(K)(0.03-0.05) and P(Cl)/P(K) ( approximately 2.0) and intracellular [Na(+)], [K(+)] and [Cl(-)]. Increased extracellular osmolarities produced hyperpolarizing shifts in E(m) in fibres studied in Cl(-)-free Ringer solution consistent with the Goldman-Hodgkin-Katz (GHK) equation. In contrast, fibres exposed to hypertonic Ringer solutions of normal ionic composition showed no such E(m) shifts, suggesting a Cl(-)-dependent stabilization of membrane potential. This stabilization of E(m) was abolished by withdrawing extracellular Na(+) or by the combined presence of the Na(+)-Cl(-) cotransporter (NCC) inhibitor chlorothiazide (10 microM) and the Na(+)-K(+)-2Cl(-) cotransporter (NKCC) inhibitor bumetanide (10 microM), or the Na(+)-K(+)-ATPase inhibitor ouabain (1 or 10 microM) during alterations in extracellular osmolarity. Application of such agents after such increases in tonicity only produced a hyperpolarization after a time delay, as expected for passive Cl(-) equilibration. These findings suggest a model that implicates the NCC and/or NKCC in fluxes that maintain [Cl(-)](i) above its electrochemical equilibrium. Such splinting of [Cl(-)](i) in combination with the high P(Cl)/P(K) of skeletal muscle stabilizes E(m) despite volume changes produced by extracellular hypertonicity, but at the expense of a cellular capacity for regulatory volume increases (RVIs). In situations where P(Cl)/P(K) is low, the same co-transporters would instead permit RVIs but at the expense of a capacity to stabilize E(m).

Animals↗
PubMed1997

Sodium-independent inward chloride pumping in rat cardiac ventricular cells.

The intracellular Cl concentration ([Cl]i) in rat cardiac ventricular muscle, measured with double-barreled microelectrodes in vitro, was 21.3 +/- 1.5 (SD) mM [number of observations (n) = 46]. With the Na-K-Cl cotransport inhibitor bumetanide (10 microM), it fell to 13.4 +/- 1.4 mM (n = 27), and with 1 mM acetazolamide, it fell further, to 7.2 +/- 1.5 mM (n = 5), close to equilibrium with the membrane potential. In the absence of Na, [Cl]i was 15.9 +/- 1.4 mM (n = 8), and with 1 mM acetazolamide, it fell to 6.5 +/- 0.6 mM (n = 4), again close to equilibrium. The bumetanide- and Na-insensitive components of inward Cl pumping were inhibited by chlorothiazide and ethacrynic acid but were unaffected by the Na-Cl cotransport inhibitor metolazone. There was inhibition of Na-K-Cl cotransport by chlorothiazide = acetazolamide > metolazone. The anion exchange inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid and HCO3 had no effect on [Cl]i in any condition. Thus Cl accumulation in the rat ventricle is fully accounted for by two systems, namely, Na-K-Cl cotransport and an Na-independent, possibly primary active, process.

Acetazolamide↗
PubMed1993

Stimulation of alpha 2-adrenergic receptors increases Na(+)-K(+)-ATPase activity in distal convoluted tubule cells.

The influence of alpha-adrenoceptor subtypes on Na+ transport in distal convoluted tubules (DCT) has not been examined due to the difficulty of isolating and quantifying responses in this segment. These experiments were designed to test the hypothesis that alpha-adrenergic receptors stimulate Na+ absorption in DCT cells. Norepinephrine and epinephrine increased 22Na+ uptake into immortalized mouse DCT cells by 49 and 55% compared with basal uptake. Selective alpha 2-agonists (guanabenz, clonidine, and B-HT 933) stimulated 22Na+ uptake by 39-45%, but alpha 1-agonists had no effect. alpha 2-Agonist-stimulated 22Na+ uptake was abolished with alpha 2-antagonists (yohimbine, idazoxan). The entry pathways for alpha 2-agonist-stimulated 22Na+ uptake were determined with the NaCl cotransport inhibitor, chlorothiazide (10(-4) M), and the Na+ channel blocker, amiloride (10(-6) M). Agonist-stimulated 22Na+ uptake was inhibited 42 +/- 5 with chlorothiazide and 47 +/- 7% with amiloride. These results suggested that alpha 2-receptors may activate Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase), resulting in an increased driving force for luminal Na+ entry through both pathways. Ouabain-suppressible 86Rb uptake and intracellular Na+ activity ([Na+]i; measured in single cells on glass cover slips loaded with the fluorescent probe sodium-binding benzofuran isophthalate) were used to measure Na(+)-K(+)-ATPase activity. alpha 2-Agonists significantly increased 86Rb uptake within 30 s. After 2.5 min, epinephrine and B-HT 933 decreased [Na+]i from a control level of 13 +/- 1 to 5 +/- 1 mM.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effects of thiazide diuretics on the lipid profile of infants with bronchopulmonary dysplasia.

Hyperlipidemia has been reported in some infants with bronchopulmonary dysplasia (BPD) who received thiazides for extended periods. In this prospective, controlled trial, we studied 17 infants with BPD who received diuretic therapy and 26 control infants who did not receive diuretics. Plasma triglycerides, total cholesterol and high-density lipoprotein (HDL) cholesterol were measured enzymatically prior to onset of diuretic therapy in the study group of infants and on the day of recruitment into the study in control infants, and every 2 weeks thereafter. Plasma low-density lipoprotein cholesterol concentrations were calculated. At the end of 4 weeks, plasma lipid concentrations were comparable in both groups of infants except for significantly higher plasma HDL cholesterol concentrations observed in infants who received chlorothiazide (39 +/- 15 vs. 30 +/- 6 mg/dl, p less than 0.05). Short-term administration of chlorothiazide to infants with BPD is not associated with clinically significant changes in plasma lipid concentrations.

Analysis of Variance↗
PubMed1980

Hyperuricemia induced by some antihypertensives and uricosuric drugs in oxonate-treated rats.

Effects of antihypertensive and uricosuric drugs were studied on the plasma and urinary levels of uric acid in oxonate-treated rats. We made use of animals with a catheterized aorta to successfully collect blood samples and this procedure simplified the evaluation of progressive changes of plasma uric acid, under successive loading with potassium oxonate. The plasma uric acid level of the oxonate-treated rats was increased even with a single administration of diuretic chlorothiazides, furosemide, diazoxide and also uricosuric drugs such as tienilic acid and probenecid. On the other hand, a wellmaintained plasma uric acid level was also produced by exogenously administered uric acid in rats which had been given allopurinol and potassium oxonate. Diazoxide, tienilic acid and probenecid increased the plasma uric acid, while diuretic chlorothiazides did not. Furosemide tended to decrease the plasma uric acid level at the early stage of administration to rats treated with allopurinol, oxonate and uric acid, but increased these levels several hours later when the effect was studied by uric acid loading test wit rats treated with allopurinol and oxonate. These effects also appeared as changes in the urine-excreted uric acid. Thus, the oxonate-treated rats demonstrated an acutely induced hyperuricemia not only with certain antihypertensives, but also with uricosuric drugs. The utility of these procedures for evaluating the hyperuricemic and uricosuric effects of drugs is discussed.

Allantoin↗
PubMed1983

Monotherapy in the treatment of hypertension.

Approximately 600 people with mild to moderate hypertension were treated with a regimen that started with monotherapy. Reduction in sodium intake achieved adequate blood pressure control in 38 percent, higher than that achieved without therapy (17 percent). Chlorothiazide and propranolol gave satisfactory blood pressure control in 43 and 56 percent of patients, respectively, as sole therapy. When initial blood pressure was greater than 110 mm Hg, satisfactory control was achieved in fewer patients (sodium restriction, 13 percent; chlorothiazide, 30 percent, propranolol 38 percent); in this group, therapy with reduction of sodium intake alone is rarely effective. All measures were about equally successful in treating isolated systolic hypertension. The group given thiazide diuretics alone had an increased number of deaths from myocardial infarcts compared with other groups. This was not seen if a beta-blocking drug or a centrally-acting drug was used in conjunction with the thiazide diuretic. Monotherapy can successfully reduce blood pressure in most patients with mild hypertension. No regimen can be stated to be unequivocally superior to another.

Benzothiadiazines↗
PubMed1993

[Some effects of pH, diuretics and organic acids on the uptake of oxalate in a renal tubular cell line (LLC-PK1)].

The effects of changes in extracellular pH and treatments with diuretics or some organic acids on the uptake of oxalate were studied in an epithelial cell line of renal origin (LLC-PK1 cells). The oxalate uptake into the cells exhibited a marked sensitivity to extracellular, pH, in the present results with acidic pH stimulating and alkaline pH inhibiting the DIDS sensitive uptakes. The uptake of oxalate was clearly inhibited by DIDS, proportionally to the concentrations from 10 microM to 1 mM. Furosemide, chlorothiazide, probenecid and acetazolamide inhibited the oxalate uptake significantly. Probenecid has the most potency on the inhibition of the uptake in high concentrations, and acetazolamide needed a high concentration for the small effect. However, allopurinol has no effect on the uptake as well as dicarboxylates (malate, succinate and phenyl succinate) and organic acids (urate and para-amino hippurate). We discussed the mechanisms of the inhibition against the oxalate uptake concerning with each drug. It was suggested that probenecid may inhibit the oxalate carriers directly, while furosemide, chlorothiazide and acetazolamide may inhibit then by the direct actions and some secondary effects which are provided by those drugs.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2000

Interaction and transport of thiazide diuretics, loop diuretics, and acetazolamide via rat renal organic anion transporter rOAT1.

The renal tubular secretion of thiazides and loop diuretics via the organic anion transport system in renal tubules is required for them to reach their principal sites of action. Similarly, acetazolamide, a diuretic clinically administered for glaucoma, is excreted from the kidney by glomerular filtration and tubular secretion. In this study, we investigated the interaction and transport of these diuretics via the rat renal organic anion transporter rOAT1 by using Xenopus laevis oocyte expression system. p-[(14)C]Aminohippurate (PAH) uptake by rOAT1-expressing oocytes was inhibited in the presence of a thiazide (chlorothiazide, cyclothiazide, hydrochlorothiazide), a loop diuretic (bumetanide, ethacrynic acid, furosemide), or a carbonic anhydrase inhibitor (acetazolamide, ethoxzolamide, methazolamide). Dixon plot analysis demonstrated that the inhibition constant (K(i)) value was 1.1 mM for acetazolamide, 150 microM for hydrochlorothiazide, 9.5 microM for furosemide, and 5. 5 microM for bumetanide. Kinetic analysis revealed that acetazolamide inhibited rOAT1 competitively and that inhibition style of furosemide was a mixture of competitive and noncompetitive. [(14)C]PAH efflux was significantly enhanced when the rOAT1-expressing oocytes were incubated in the presence of unlabeled PAH, alpha-ketoglutarate, acetazolamide, chlorothiazide, or hydrochlorothiazide. rOAT1 stimulated acetazolamide uptake, which was inhibited by probenecid. Although the loop diuretics had little trans-stimulation effect on [(14)C]PAH efflux via rOAT1, the rOAT1-mediated furosemide uptake was observed. These findings suggest that rOAT1 contributes, at least in part, to the renal tubular secretion of acetazolamide, thiazides, and loop diuretics.

Acetazolamide↗
PubMed1980

Cardiovascular effects of indapamide on frog hearts and open-chest cats.

Unlike related diuretics indapamide has been found by some investigators to be associated with a mild reduction in heart rate during its use as an antihypertensive agent. This investigation concerns the attempt to duplicate this phenomenon in animals and to elucidate possible mechanisms. In isolated frog hearts, high concentrations (0.3 mM) of indapamide decreased contractions 21.7 +/- 1.2% and rate 9.1 +/- 1.0%. This effect was not observed with chlorothiazide, acetazolamide, or furosemide and was not altered by atropine. Also in the frog heart, 0.03 mM indapamide reduced the stimulatory effects of isoproterenol and calcium ion and enhanced the inhibitory action of acetylcholine. In open-chest cats, after 30 min, indapamide (3 mg/kg, i.v.) elicited minor decreases in heart rate, aortic flow, and mean carotid pressure. When arterial pressure was rapidly reduced by acetylcholine (5 microgram/kg, i.v.) the resultant rise in aortic flow was significantly diminished by indapamide pre-treatment. Antifibrillatory activity was measured in the open-chest cat by determining the minimum electrical current, delivered to the right atrium, required to induce atrial fibrillation. Quinidine (5 mg/kg, i.v.) and chlorothiazide (10 mg/kg, i.v.) raised the fibrillatory threshold 94.3 +/- 10.1 % and 45.1 +/- 4.0 % respectively while indapamide displayed minimal activity.

Acetylcholine↗
PubMed1963

A comparison of the use of Aldactone and Aldactone A in the treatment of hepatic ascites.

In eight patients with cirrhosis and stable ascites controlled on chlorothiazide and spironolactone, a small particle preparation of spironolactone (Aldactone A) was as effective, at one quarter the dosage, as conventional spironolactone (Aldactone). Plasma spironolactone metabolite levels and urinary excretion of spironolactone metabolite were equivalent with both preparations. The variable dosage requirement of spironolactone in patients with cirrhosis and ascites is discussed in relation to these observations.

Ascites↗
PubMed1965

SIGNIFICANCE OF PLATELET ANTIBODIES IN NEONATAL THROMBOCYTOPENIC PURPURA AFFECTING A PAIR OF SIBLINGS.

A pair of siblings, both of whom had neonatal thrombocytopenic purpura, are described. During the first pregnancy, the mother was given chlorothiazide and the implications of this therapy are considered. At the end of the second pregnancy a platelet iso-antibody was detected in the maternal serum. The possible reason for not detecting this antibody in the serum of the second child is considered.

Antibodies↗
PubMed1963

THE METABOLISM OF THE VOLATILE AMINES. IV. THE ROLE OF DRUGS IN THE PATHOGENESIS OF HEPATIC ENCEPHALOPATHY.

The effects of certain drugs on metabolism of ammonia by the liver and kidneys in dogs were investigated by a technique in which both hepatic inflow and outflow bloods could be repeatedly sampled in unanesthetized healthy animals. Specific representatives of the classes of the drugs studied included thiopental (barbiturates), morphine (opiates and analgesics), promazine (tranquillizers), and chlorothiazide (oral diuretics).The three drugs commonly used as sedatives were all found to impair the ability of the liver to metabolize ammonia. The diuretic, by contrast, increased the amount of ammonia put into the systemic system by the kidneys. Ethanol appeared to have little or no direct effect on ammonia metabolism.The possibility exists that the occurrence of acute hepatic encephalopathy in patients with severe liver disease may be avoided in many cases if these drugs are administered with proper care. Results also indicated that current concepts of the pharmacological action of sedatives, opiates and tranquillizers may require revision.

Amines↗
PubMed1964

SULFONAMYL DIURETICS--MECHANISM OF ACTION AND THERAPEUTIC USE.

The mechanism whereby sulfonamyl diuretics are effective is through the blockage of the renal tubular reabsorption of chloride. The excretion of sodium, potassium and water is a passive one to maintain ionic equilibrium. Chlorothiazide has been shown to be almost ineffective as a diuretic agent per se. Although it does block a moiety of the renal tubular reabsorption of bicarbonate, the effect is merely a transient one.

Acetazolamide↗
PubMed1964

RESPONSE OF THE INFANT KIDNEY TO DIURETIC DRUGS.

The diuretic response of normal infants, 6 to 47 days of age, to single doses of mercaptomerin, chlorothiazide, acetazolamide, triamterene and spironolactone was studied by following urinary electrolytes, pH and osmolality. Peak diuresis occured two to four hours after drug administration, and because of compensatory mechanisms little change in urinary excretion was found if only 24-hour urines were studied. Mercaptomerin increased sodium excretion seven-fold, compared to three- to four-fold increases for the other diuretics. Control urinary Na:K ratios averaged 0.68 in infants compared to 2.8 for adults, and mercaptomerin produced the largest increase in this ratio. Qualitatively the response to diuretics is the same in newborn in the ages studied as it is reported to be for adults; no immaturity of the infant kidney in this regard was demonstrated.

Acetazolamide↗
PubMed2000

Na(+) and Cl(-) transport by the urinary bladder of the freshwater rainbow trout (Oncorhynchus mykiss).

Freshwater (FW) rainbow trout (Oncorhynchus mykiss) urinary bladders mounted in vitro under symmetrical saline conditions displayed electroneutral active absorption of Na(+) and Cl(-) from the mucosal side; the transepithelial potential (V(t)) was 0.1 mV, and the short-circuit current was less than 1 microA cm(-2). Removal of Na(+) from mucosal saline decreased Cl(-) absorption by 56% and removal of Cl(-) decreased Na(+) absorption by 69%. However, active net absorption of both Na(+) and Cl(-) was not abolished when Cl(-) or Na(+) was replaced with an impermeant ion (gluconate or choline, respectively). Under physiological conditions with artificial urine (¿Na(+) = 2.12 mM, ¿Cl(-) = 3.51 mM) bathing the mucosal surface and saline bathing the serosal surface, transepithelial potential (V(t)) increased to a serosal positive approximately +7.6 mV. Unidirectional influx rates of both Na(+) and Cl(-) were 10-20-fold lower but active absorption of both ions still occurred according to the Ussing flux ratio criterion. Replacement of Na(+) with choline, or Cl(-) with gluconate, in the mucosal artificial urine yielded no change in unidirectional influx of Cl(-) or Na(+), respectively. However, kinetic analyses indicated a decrease in maximum Na(+) transport rate (J(max)) of 66% with no change in affinity (K(m)) in the low Cl(-) mucosal solution relative to the control solution. Similarly, there was a 79% decrease in J(max) values for Cl(-), again with no change in K(m), in the low-Na(+) mucosal bathing. The mucosal addition of DIDS, amiloride or bumetanide (10(-4) M) had no effect on either Na(+) or Cl(-) transport, under either symmetrical saline or artificial urine/saline conditions. Addition of the three drugs simultaneously (10(-4) M), or chlorothiazide (10(-3) M), under symmetrical saline conditions also had no effect on Na(+) or Cl(-) transport rates. Cyanide (10(-3) M) addition to mucosal artificial urine caused a slowly developing decrease of Na(+) influx to 59% and Cl(-) influx to 50% in the period after drug addition. Na(+) and Cl(-) reabsorption appears to be a partially coupled process in the urinary bladder of O. mykiss; transport mechanisms are both dependent upon and independent of the other ion.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMedDate not supplied

Carbonic anhydrase-immobilized precolumn for selective on-line sample pretreatment in high-performance liquid chromatographic determination of certain sulphonamide drugs.

Carbonic anhydrase (CA)-immobilized aminopropyl silica precolumn was developed for direct injection determination of certain sulphonamide drugs in biological fluids by column-switching (CS) high-performance liquid chromatography. Under the optimized conditions, only the sulphonamide drugs with an unsubstituted sulphonamide group were retained on the CA precolumn and separated on a reversed-phase analytical column. Of these, the retention of hydrochlorothiazide (HCT), chlorothiazide, acetazolamide, furosemide (FS) and chlorthalidone was almost quantitative. The peak area of HCT was proportional to the concentration in the range of 1-100 nmol/mL with relative standard deviations of 3.7% (5 nmol/mL) and 0.7% (100 nmol/mL). This CS system was applied to urine and plasma samples spiked with HCT and FS. Endogenous components of these were effectively removed, and HCT and FS were selectively retained on the CA precolumn. Almost quantitative recoveries and reproducibility were obtained.

Acetazolamide↗
PubMed1980

Quantitation of acetazolamide in plasma by high-performance liquid chromatography.

A method for estimating acetazolamide concentrations in human plasma is described. Buffered plasma (pH 4.8) containing chlorothiazide as an internal standard is extracted twice with ethyl acetate. The extract is evaporated, redissolved, and chromatographed on silica gel with hexane-chloroform-methanol-acetic acid (65:25:10:0.25) as the mobile phase. The extraction efficiencies were greater than 90%, the coefficients of variation at 1 and 30 micrograms/ml of plasma were 3.5 and 2.0%, respectively, and the calibration curves were linear and had an intercept of essentially zero. The suitability of the method for pharmacokinetic studies was verified in a normal volunteer dosed with 250-mg (solution) and 500-mg (sustained-release tablet) acetazolamide formulations.

Acetazolamide↗
PubMed1995

Mechanisms of fluid and ion secretion by the parotid gland of the kangaroo, Macropus rufus, assessed by administration of transport-inhibiting drugs.

Possible mechanisms of primary fluid formation by macropodine parotid glands were investigated in anaesthetized red kangaroos using ion transport inhibitors. Carotid plasma amiloride concentrations of 0.05-0.5 mmol.l-1 progressively reduced a stable acetylcholine-evoked half-maximal flow rate of 2.0 +/- 0.04 to 0.22 +/- 0.024 ml.min-1 (mean +/- SEM). Concurrently, saliva bicarbonate concentration and secretion fell (135 +/- 1.6 to 67 +/- 1.7 mmol.l-1 and 272 +/- 7.6 to 15 +/- 2.6 mumol.min-1, respectively); [phosphate], [chloride] and [sodium] rose and [potassium] and osmolality were unaltered. High-rate cholinergic stimulation did not increase saliva flow beyond 11 +/- 1.0% of that for equivalent pre-amiloride stimulation. Equipotent levels of amiloride and methazolamide given concurrently were no more effective at blocking flow and bicarbonate secretion than when given separately. Furosemide (up to 2 mmol.l-1), bumetanide (up to 0.2 mmol.l-1) and ethacrynate (1 mmol.l-1) in carotid plasma had no effect on salivary flow or ion concentrations. During methazolamide blockade, furosemide did not curtail the concurrent increase in salivary [chloride]. Chlorothiazide at 0.25-1.0 mmol.l-1 caused progressive depression of saliva flow and [bicarbonate], and elevation of [chloride]. 4-acetamido-4'-isothiocyanatostilbene-2,2'disulphonic acid at 0.1 mmol.l-1 was without effect, whereas at 0.5 mmol.l-1 it stimulated fluid secretion and increased saliva [protein], [sodium], [potassium], [bicarbonate] and osmolality. Concurrently, mean arterial blood pressure and pulse pressure fell and heart rate, haematocrit and carotid artery plasma flow rose. These responses were absent if saliva flow was kept constant by reduction in cholinergic stimulation during 4-acetamido-4-isothiocyanatostilbene-2,2'disulphonic acid administration. It is concluded that secretion of primary fluid by the kangaroo parotid is initiated mainly (> 90%) by secretion of bicarbonate which is formed in the endpiece cells from CO2 delivered by the circulation. No evidence was found for initiation of fluid secretion by chloride transport involving basolateral Na(+)-K(+)-2Cl- symports, Na(+)-Cl- symports or Cl-/HCO3- antiports.

Amiloride↗