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PubMed1983

Urinary zinc excretion, diuretics, zinc deficiency and some side-effects of diuretics.

Diuretics which principally act in the first portion of the distal convoluted tubule, such as the thiazides and chlorthalidone, significantly increase the urinary excretion of zinc. The potassium-retaining diuretic amiloride reduced urinary zinc excretion significantly. The hyperzincuria provoked by common distal tubular diuretics can cause zinc deficiency, especially when other aetiological factors such as alcoholism, renal insufficiency and pregnancy are also present. Zinc deficiency may be expressed clinically by hypogeusia, hyposmia, sexual impotence or delayed healing; the latter might be an important factor in cases of myocardial infarction.

Adult↗
PubMed1988

Effects of ototoxic diuretics (loop diuretics) on the endolymphatic sac.

The acute and chronic effects of treatment with ethacrynic acid (EA) and furosemide (FU) on the structure of the murine endolymphatic sac were studied by means of light and transmission electron microscopy. The animals were treated with loop diuretics in doses which are known to cause morphological alterations of the stria vascularis and a significant reduction of the endocochlear potential. A single intravenous injection of either EA or FU resulted in immediate morphological changes such as an increase in cytoplasmic contents of endoplasmic reticulum and more prominent Golgi structures of the light cells. These cells developed membrane-bound granules and a smooth tubular network in the apical cytoplasm. These findings together with the appearance of a precipitate on the luminal aspect of the cell membrane suggested secretory activity. Ten days after daily intraperitoneal injections with loop diuretics in subtoxic doses, the epithelial cytoarchitecture of the endolymphatic sac was altered, with pronounced veiling of the light cells by the dark cells. It is concluded that the changes in the endolymphatic sac epithelium after treatment with ototoxic diuretics may not be a result of a primary toxic effect on the sac per se, but rather be secondary to alterations in fluid and ion homeostasis in the rest of the inner ear.

Animals↗
PubMed1987

Pharmacokinetic-pharmacodynamic relationship of piretanide in healthy and uremic subjects. Determinants of the diuretic effect of a loop diuretic.

The pharmacokinetics of the loop diuretic piretanide and its diuretic effects were studied in 6 healthy volunteers, 12 pre-dialysis (GFR 7-28 ml/min) and 10 dialysis patients (c-creat. 1-7 ml/min). Single doses up to 96 mg i.v. and orally were well tolerated and audiometry showed no hearing changes. Pharmacokinetic data showed rapid and almost complete absorption (bioavailability 92%) and a rapid elimination with renal clearance of 50% of the total 200 ml/min in the normals and renal clearance of about 50% of actual GFR in the patients. Extrarenal clearance was the same in normals and patients. The rapid extrarenal elimination reduces the risk of accumulation in renal patients but also reduces the active fraction of the dosage being cleared by the kidneys. Therefore, a high dosage and high plasma levels of piretanide were necessary for diuretic effect in uremic patients. The relation between the urinary piretanide excretion rate and the chloruretic effect was similar in normals and uremic patients; Cl- excretion increased 40 mMol per mg piretanide excreted.

Adult↗
PubMed1977

[Effects of a beta-adrenolytic and a diuretic vis-à-vis hyper-reninemia induced by isoprenaline in anesthetized dogs. Value of beta blocking-diuretic interaction].

Intravenous injection of isoproterenol increases plasma renin activity (PRA) in anesthetized dogs. S. 464, a new beta adrenergic blocking agent, injected five minutes before isoproterenol, inhibits plasma renin hyperactivity. On the other hand, teclothiazide, a thiazide diuretic, induces no significant modification of the isoproterenol-induced increase of PRA. The combination of both compounds (five parts of S. 464, one part of diuretic), assumes the same inhibitory effects as S. 464 alone. These results and other experimental data (antihypertensive and diuretic activities) are discussed and explain the interest of such an association as a rational therapy of arterial hypertensive disorders.

Adrenergic beta-Antagonists↗
PubMed1985

Adrenergic hyposensitivity during long-term diuretic therapy--a possible explanation for the antihypertensive effect of diuretics?

The long-term effect of hydrochlorothiazide on beta 2-adrenoceptor density on mononuclear cells was investigated in 10 male patients with essential hypertension. There was a 40% reduction in beta 2-adrenoceptor density but no change in receptor affinity. This down-regulation of beta 2-adrenoceptors may explain the observed adrenergic hyposensitivity after long-term diuretic therapy. If lymphocytic beta 2-adrenoceptors represent presynaptic beta-adrenoceptors, a down-regulation of presynaptic beta 2-receptors may occur too, and result in a decrease of adrenergic transmitter release. Under this assumption long-term diuretic treatment causes its antihypertensive effect by modulating adrenergic sensitivity at the receptor level on the presynaptic side leading to an attenuated response to pressor hormones on the postsynaptic vascular side.

Adult↗
PubMed1985

Effects of a thiazide diuretic (hydroflumethiazide) and a loop diuretic (bumetanide) on the endocrine pancreas: studies in vitro.

Treatment with thiazide diuretics causes an impairment of the glucose metabolism. To study whether this is due to a direct effect on the endocrine pancreas, the effects of the thiazide hydroflumethiazide on the release of glucagon, insulin, and somatostatin from the isolated perfused pancreas of normal and alloxan diabetic dogs were examined. Hydroflumethiazide at concentrations ranging from 1 to 50 micrograms/mL stimulated the normal secretion of glucagon (P less than 0.001), insulin (P less than 0.001), and somatostatin (P less than 0.001) in a dose-dependent manner. The normal hormone responses evoked by 50 micrograms/mL of the thiazide were, however, modified by the prevailing glucose level: higher insulin (P less than 0.05) and somatostatin (P less than 0.05) and lower glucagon (P less than 0.05) were obtained at the high glucose concentration of 11 mmol/L rather than at the low glucose concentration of 1.3 mmol/L. In alloxan diabetes, insulin secretion was almost extinct and did not respond to hydroflumethiazide, whereas glucagon was dose-dependently stimulated (P less than 0.001). In addition, we looked at the effect of the loop diuretic, bumetanide. The infusion of bumetanide at doses ranging from 0.5 to 3 micrograms/mL did not alter the release of glucagon, insulin, and somatostatin in the presence of 5.5 mmol/L glucose. The results suggest that hydroflumethiazide possesses the ability to directly stimulate A cell secretion in the normal and alloxan diabetic pancreas. Whether this effect is of clinical importance for the diminution in glucose tolerance observed during thiazide therapy remains, however, uncertain.

Animals↗
PubMed1981

(Acylaryloxy)acetic acid diuretics. 3. 2,3-Dihydro-5-acyl-2-benzofurancarboxylic acids, a new class of uricosuric diuretics.

The discovery that dihydroethacrynic acid and other (4-acylphenoxy)acetic acids possessed modest but significant uricosuric and diuretic activity prompted our investigation of the related 2,3-dihydro-5-acyl-2-bensofurancarboxylic acids. Synthetic routes to a number of these compounds are presented along with the structure-activity relationships generated from studies in rats, dogs, and chimpanzee. Examination of the enantiomers of 6,7-dichloro-2,3-dihydro-5-(2-thienylcarbonyl)-2-benzofurancarboxylic acid (10c) in the chimpanzee revealed that all diuretic and saluretic activity is due to the (+) enantiomer 10d, while the (-) enantiomer 10e is responsible for all of the uricosuric activity. X-ray analysis showed that the (-) enantiomer 10e possesses the 2R configuration.

Animals↗
PubMed1980

Synthesis and diuretic profile of 3-(3-amino-1,2,4-oxadiazol-5-yl)-5-chloro-2,6-pyrazinediamine, an amiloride-type diuretic.

The synthesis of an analogue of amiloride in which the acylguanidine moiety has been replaced by a 1,2,4-oxadiazol-3-amine unit is described. This substance (3, CGS 4270) exhibited a diuretic profile similar to that of amiloride when evaluated in the rat and the dog. In the rat, combination with hydrochlorothiazide increased diuresis and saluresis and returned potassium levels to control values. A series of 5-aryl-1,2,4-oxadiazol-3-amines not directly related to amiloride was prepared, but these substances had no diuretic activity.

Animals↗
PubMed1988

Binding of loop diuretics to their renal receptors: use as a screening model for potential diuretic activity.

Loop diuretics of the benzoic acid and aryloxyacetic acid families inhibit Na+K+Cl- cotransport. The ranking order of potencies measured in the thick ascending limb of Henle's loop and the ranking order of affinities for [3H]piretanide receptors on renal plasma membranes are the same. Potencies and affinities correlate well (correlation coefficient r = 0.959 for the medulla and r = 0.951 for the cortex). Therefore, measurement of [3H]piretanide binding is proposed to facilitate screening for loop diuretic action.

Animals↗
PubMed2000

Diuretics and vitamin B1: are diuretics a risk factor for thiamin malnutrition?

Despite modern pharmacologic agents in the therapy of heart failure, the prevalence of heart failure is increasing worldwide. In the vitamin B1 deficiency disease beriberi, cardiac symptoms may represent the central feature. Two new studies confirmed that all diuretics lead to increased urinary thiamin excretion depending on the urinary flow rate. In a subject at risk, such as an elderly patient, chronic diuretic treatment may lead to a subclinical thiamin deficiency. Whether subclinical thiamin nutriture is a modulator of the prevalence and/or severity of heart failure is not known; however, it seems to be plausible from the metabolic point of view.

Diuretics↗
PubMed1999

[Diagnostic comparison of diuretic isotopic renogram and diuretic Doppler ultrasonography in pediatric hydronephrosis].

UNLABELLED: Due to the high frequency of asymptomatic pyelocaliceal dilatations, most of them with prenatal diagnosis, the diagnosis of obstruction remains a major chance. Isotopic diuretic renogram (IDR) remains the basic diagnostic tool, although it has some pitfalls and undetermined diagnosis. To obviate them, several others tests have been used, such as diuretic Doppler ultrasound (DDU). The object of this paper is to determine its validity. METHODS: All the patients with hydronephrosis and with grade II dilatation or bigger were studied wit DDU. The results were compared with those obtained by IDR, obtaining 2 x 2 tables to analyze specificity and sensibility. RESULTS: 37 patients were studied, 9 of them bilateral, with a total of 46 dilated kidneys. There were 22 males and 15 females. 59 percent had prenatal diagnosis and 57 percent were asymptomatic. 22 percent had grade IV dilatation, 37 percent grade III and 41 percent grade II. 2 cases had contralateral vesicoureteral reflux. IDR showed 15 obstructed kidneys, 7 of them with a regular renal function. 16 were operated, one more due to abdominal pain despite a non-obstructed IDR. Only 7 of the 15 kidneys presented an obstructive pattern in the DDU. Comparing both tests, DDU had a 46 percent of sensibility and 100 percent of specificity and a negative predictive value of 79% for a 95% interval. Kramer index was 0.54 representing a very low association. CONCLUSIONS: In our institution, DDU is not better than IDR to diagnose obstruction. We consider its use as a second line test in cases of doubtful IDR.

Age Factors↗
PubMed1995

Functional expression of a diuretic hormone receptor in baculovirus-infected insect cells: evidence suggesting that the N-terminal region of diuretic hormone is associated with receptor activation.

A recombinant baculovirus containing the diuretic hormone receptor cDNA from Manduca sexta was constructed. When Spodoptera frugiperda (Sf9) cells were infected with the virus, a time-dependent expression of the receptor appeared. The expressed receptor displayed high affinity for diuretic hormone, which was similar to the affinity observed in Malpighian tubules and transfected COS-7 cells. The receptor expression level was 77 pmol/mg protein, as compared to 3.1 pmol/mg protein in Malpighian tubules and 1.3 pmol/mg protein in transfected COS-7 cells. Chemical crosslinking of 125I-labeled Mas-DH to the expressed receptor revealed a protein of 48-52 kDa. Furthermore, Mas-DH stimulated cAMP synthesis in recombinant baculovirus infected Sf9 cells. The N-terminal truncated analog [13-41] Mas-DH bound to the expressed receptor with high affinity but did not stimulate cAMP synthesis. This suggests that the N-terminal region of Mas-DH is required for receptor activation but not receptor binding. The recombinant baculovirus provides an alternate system to study receptor function and will allow large scale production of receptor for biophysical characterization.

Animals↗
PubMed1988

Cyclic AMP: a second messenger of the newly characterized AVP-like insect diuretic hormone, the migratory locust diuretic hormone.

An AVP-like neurohormone was extracted from suboesophageal and thoracic ganglia of Locusta migtatoria, isolated, characterized and synthesized. It functions as a diuretic hormone in this species by enhancing the excretion of urine from the MT. It appears to act by increasing cyclic AMP; synthetic AVP-like IDH increases cyclic AMP of the MT in vitro in a time-dependant, dose-dependant and very specific manner. 8-BR-cyclic AMP, an analog of cyclic AMP known to enter the cells, mimics the diuretic action of the AVP-like IDH. Furthermore, the combined actions of forskolin (the activator of the adenylate cyclase) and IBMX (the inhibitor of the phosphodiestherase activity) increase both MT cyclic AMP level and excretion of the primary urine. We conclude from these results that cyclic AMP is a second messenger of the AVO-like IDH.

1-Methyl-3-isobutylxanthine↗
PubMed1986

A comparison of the pharmacokinetics and diuretic effects of two loop diuretics, torasemide and furosemide, in normal volunteers.

The diuretic effects of torasemide and furosemide at three different steady-state plasma and urinary drug levels were compared in a randomized cross-over study in 6 healthy volunteers. Each trial with either torasemide or furosemide consisted of four consecutive periods of 90 min, the first being a control period, and during the three other periods, increasing doses of drug were administered. Each 90-min period was itself divided into three 30 min blood sampling and urinary collection periods. The urinary losses of water and electrolytes were compensated within each 30-min period by intravenous infusion of saline (NaCl) and 5% glucose solutions, to which KCl was added. A constant dose of calcium gluconate was given to compensate, at least in part, any calcium loss. Data from each 30 min control and the 3 drug dose periods, corresponding to full steady-state conditions, were used for clearance determinations and measurement of plasma and urinary drug concentrations. Urine volume, osmolar clearance, absolute and fractional urinary excretion of sodium, potassium, chloride, calcium and magnesium and creatinine clearance increased similarly after torasemide and furosemide according to the logarithm of the dose of the drug. Free water clearance stabilized at a constant level with torasemide and increased continuously after each dose of furosemide. During each of the three drug administration periods, the plasma levels of torasemide were not significantly different from those of furosemide, whereas the urinary concentrations and absolute excretion rates of torasemide were more than 5-times lower than those of furosemide.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Diuretic action of the novel loop diuretic torasemide in the presence of angiotensin II or endothelin-1 in anaesthetized dogs.

The effects of torasemide (0.1 and 1 mg kg-1, i.v.) and furosemide (3 mg kg-1) on renal haemodynamics and excretory responses in the presence of angiotensin II and endothelin-1 was examined in anaesthetized dogs. Angiotensin II or endothelin-1 was continuously infused into the renal artery throughout the experiment and a bolus of torasemide or furosemide was injected into the bracheal vein. Continuous intrarenal arterial (i.r.a.) infusion of angiotensin II, at a dose of 5 ng kg-1 min-1, increased renal vascular resistance (RVR) and decreased renal blood flow (RBF) and glomerular filtration rate (GFR), but had no effect on systemic mean arterial pressure (MAP). Urinary excretion of sodium (UNaV) and urine flow (UF) were significantly decreased during angiotensin II infusion. Intravenous injections of torasemide in the presence of angiotensin II caused a dose-dependent increase in UF, UNaV and urinary excretion of potassium (UKV), while a decrease in RVR was accompanied by an increase in RBF. UKV was greater in the furosemide group than in the torasemide group, despite both groups having the same degree of aquaresis and natriuresis. Continuous i.r.a. infusion of endothelin-1, 1.5 ng kg-1 min-1, produced effects similar to those of angiotensin II on renal haemodynamics; however, the onset of action was extremely slow compared with the effects produced by angiotensin II. Endothelin-1 caused a significant decrease in UF, UNaV and UKV only at a later period, despite a relatively early depression of renal haemodynamics. Torasemide and furosemide also produced a sufficient diuretic action in this model.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1990

An open, parallel group study comparing a frusemide/amiloride diuretic and a diuretic containing cyclopenthiazide with sustained release potassium in the treatment of congestive cardiac failure--a multicentre general practice study.

A total of 71 patients with cardiac failure requiring diuretic treatment were randomly allocated to receive either 20 mg frusemide/2.5 mg amiloride or 0.25 mg cyclopenthiazide/8.1 mmol sustained release potassium once daily for 12 weeks. Of the 35 patients treated with cyclopenthiazide/potassium, in 47% of patients the daily dose was doubled compared with in only 30% of the 36 patients treated with frusemide/amiloride. Both treatments significantly improved crepitations, oedema, orthopnoea and patient self-assessments of dyspnoea on effort; there were no significant differences between the two treatments. Plasma potassium concentrations were unaffected by either treatment and there were no clinically significant changes in laboratory data. Of the five patients receiving frusemide/amiloride and of the eight receiving cyclopenthiazide/potassium who withdrew from the trial, three and four, respectively, were due to possible drug-related effects. It is concluded that frusemide/amiloride is efficacious and acceptable for the treatment of congestive heart failure.

Aged↗
PubMed1987

Diuretic action and immunological cross-reactivity of corticotropin and locust diuretic hormone.

A functional similarity and immunological cross-reactivity between adrenocorticotrophic hormone (ACTH) and a locust diuretic hormone (DH) is reported. The functional similarity is expressed in that ACTH mimics DH by stimulating fluid secretion and cyclic AMP (cAMP) secretion in locust Malpighian tubules. Desacetyl-alpha-melanocyte-stimulating hormone is active to a lesser degree but no other POMC-derived peptide tested was found to follow suit. Immunological cross-reactivity is shown by a positive response of HPLC-purified DH with a specific ACTH radioimmunoassay as well as a significant reduction in DH activity (fluid secretion) after incubations with ACTH antiserum. However, ACTH and DH are different peptides since they do not share common separation characteristics on HPLC and ACTH does not induce a high excess secretion of cAMP by the tubule cell as does DH.

Adrenocorticotropic Hormone↗