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PubMed1981

Primary hyperparathyroidism and thiazide diuretics.

Six patients receiving thiazide diuretics were referred for evaluation of mild to moderate hypercalcaemia (serum calcium 2.65-2.98 mmol/l). All patients were considered to be suffering from primary hyperparathyroidism. Withdrawal of the diuretic was followed by a reduction in the serum calcium, one patient becoming normocalcaemia. The mechanisms responsible for these changes are discussed. In hypercalcaemic patients taking thiazides, it is recommended that the effects of withholding the diuretic should be observed before more radical measures are considered.

Aged↗
PubMed1980

Effects of fasting on the diuretic response and disposition of furosemide in rats.

The influence of fasting on the relationship between the disposition and diuretic effect of furosemide was studied in rats. Fasting consisted of withholding solid food, but not water, for a period of 16 h before administering furosemide (10 mg/kg, sc) or a saline vehicle. Normally fed animals also received furosemide or the vehicle. Fasting did not modify the diuretic or the natriuretic effect (per 100 g body weight) of furosemide. The distribution of total furosemide in plasma or tissues was not affected by fasting. On the other hand, fasting which produced increasing amounts of endogenous free fatty acids in plasma and kidneys increased the concentration of free furosemide in fasting plasma but not in fasting kidney or liver of rats. The in vitro binding constant of furosemide to physiological concentrations of plasma proteins was decreased from the control value by a factor of 6.5 as a result of fasting. Neither unchanged furosemide nor its metabolite in the urine was affected by fasting. Incubation of kidney cortex tissue slices with furosemide both in the presence and absence of free fatty acid indicated an inhibition of furosemide uptake in a manner closely parallel to inhibition by probenecid. Thus, failure to observe a more pronounced diuretic and saluretic effects of furosemide in fasted rats, in spite of higher concentration of free plasma furosemide, might be due to the inhibitory effect of endogenous free fatty acids and (or) other endogenous substances on the uptake of furosemide by renal tubular cells although some homeostatic control mechanisms related to fasting could also be involved.

Animals↗
PubMed2003

Role of nitric oxide in the natriuretic and diuretic responses in pregnant rats.

Normal pregnancy is characterized by sodium conservation and increase in plasma volume, yet the natriuretic response to acute saline volume expansion (VE) is intact in pregnant rats. Nitric oxide (NO) has been suggested to play a role in renal and cardiovascular adaptations to normal pregnancy. The objective of this study was to determine the role of NO in the natriuretic and diuretic responses to VE during pregnancy. Infusion of NG-monomethyl-l-arginine (l-NMMA) was used to inhibit NO synthesis. Nine groups of Sprague-Dawley (SD) rats were studied: nonpregnant (NP-VE, n = 7), midterm pregnant (MP-VE, n = 8), and late-term pregnant (LP-VE, n = 7) SD groups that underwent VE alone after a control period; NP-l-NMMA (n = 7), MP-l-NMMA (n = 8), and LP-l-NMMA (n = 7) SD groups that were infused with l-NMMA after a control period; and another three groups of SD rats (NP-VE-l-NMMA, n = 8; MP-VE-l-NMMA, n = 7; and LP-VE-l-NMMA, n = 12) that underwent simultaneous VE and l-NMMA infusion after a control period. The change in fractional excretion of sodium was 7.22 +/- 1.03% for NPVE, 9.89 +/- 1.85% for NP-l-NMMA, and 17.66 +/- 1.85% for NP-VE-l-NMMA (P < 0.05 vs. NP-VE and NP-l-NMMA); 6.61 +/- 1.07% for MP-VE, 7.99 +/- 1.92% for MP-l-NMMA, and 10.24 +/- 1.91% for MP-VE-l-NMMA [not significant (NS) vs. MP-VE and MP-l-NMMA]; 8.20 +/- 1.92% for LP-VE, 8.09 +/- 0.70% for LP-l-NMMA, and 7.57 +/- 1.11% for LP-VE-l-NMMA (both NS vs. LP-VE and LP-l-NMMA). The increase in renal interstitial hydrostatic pressure was significantly greater in all NP compared with pregnant groups with similar experimental intervention (i.e., VE, l-NMMA, or VE-l-NMMA). In conclusion, the natriuretic and diuretic responses to VE and l-NMMA infusion were additive in NP but not in pregnant rats, indicating a possible lower ability of pregnant rats to respond to combined significant natriuretic and diuretic stimuli.

Animals↗
PubMed1991

Marked hypokalemic rhabdomyolysis with myoglobinuria due to diuretic treatment.

A 74-year-old male was admitted to hospital with acute rhabdomyolysis and myoglobinuria due to hypokalemia. The hypokalemia resulted from diuretic treatment. He had no family history of myopathy, and no diarrhea and vomiting. The neurological examination revealed painful quadriplegia. The blood pressure was 160/74 mm Hg. Laboratory examination showed hypokalemic and hypochloremic metabolic alkalosis (serum K 1.5 mEq/l, serum Cl 89 mEq/l, base excess + 20.9, HCO3- 44.9 mmol/l, pH 7.563) and marked elevations of serum CPK, LDH, GOT, GPT and myoglobin. Endocrinological and renal functions were normal. Muscle biopsy revealed marked necrosis with remarkable phagocytosis and vacuolar degeneration. The cessation of diuretics and intravenous infusion of potassium chloride resulted in a marked improvement in clinical and laboratory findings. The diuretics-induced hypokalemic myopathy is rare in the literature.

Aged↗
PubMed1982

Massive pulmonary embolism occurring with corticosteroid and diuretics therapy in a minimal-change nephrotic patient.

A 32-year-old female with a relapsing minimal-change nephrotic syndrome developed a massive pulmonary embolism during the treatment of prednisolone and diuretics. The use of diuretics in addition to a hypercoagulable state associated with nephrotic syndrome per se and corticosteroid was considered to be a direct causative factor for the event. The careful use of diuretics and a consideration of additional anticoagulant therapy are emphasized.

Adult↗
PubMed1989

Diuretic abuse and central pontine myelinolysis.

Patients with eating disorders often use diuretics to eliminate fluid to achieve lower body weight. Diuretic abuse can lead to severe hyponatremia. Central pontine myelinolysis, a disruption of the myelinated neurons of the pons, has been associated with rapid correction of severe hyponatremia. A case is presented of a 35-year-old woman who was brought to the emergency service by ambulance complaining of vomiting for 7 days and that she could not hear well because she was 'worn out'. Initial laboratory values included serum Na 91 mEq/l, K 1.6, Cl 46, bicarbonate 33, BUN 4 mg/dl, glucose 306 mg/dl. After 32 h of intravenous fluids, the serum Na was 126, K 4.0, Cl 89, bicarbonate 25, glucose 118 mg/dl. On the 3rd hospital day the serum Na was 139. On the 4th hospital day she was alert and appropriate. On the 5th hospital day, however, she was confabulating and chatty. The serum Na was 139. She progressed to develop a spastic quadriparesis, speech and swallowing difficulties. A magnetic resonance imaging scan showed central pontine myelinolysis. She acknowledged taking 400 mg daily of furosemide and drinking much water. She had a past history of anorexia nervosa. She had a residual weight phobia and strove to keep her weight below 106 lb. Her height was 5 feet, 6 inches. As illustrated by this case, diuretic abuse can cause severe hyponatremia and the subsequent risk of central pontine myelinolysis. In patients with severe chronic or subacute hyponatremia, a safe restoration rate for serum Na has been less than 0.55 mEq/l/h. Serum Na should be below 135 within the first 48 h and hypernatremia should be avoided.

Adult↗
PubMed1983

Low-dose captopril titration in patients with moderate-to-severe hypertension treated with diuretics.

To study the value of low-dose captopril (6.25 and 12.5 mg) and a diuretic combination, the blood pressure and heart rate of 17 patients with moderate-to-severe hypertension were monitored for 6 hours (hospital) or 3 hours (office) after the single low-dose or larger (25, 50, 100 and 150 mg) captopril dosage. All patients had preserved renal function and were taking an oral diuretic (hydrochlorothiazide or furosemide) for at least 4 weeks. The supine and upright acute blood pressure lowering with 6.25 mg was not different from the larger captopril doses; none produced persistent or profound hypotension. There was no deterioration of renal function, new or persistent increase in proteinuria, neutropenia or agranulocytosis acutely or during 17 +/- 2 weeks of follow-up. Low-dose captopril (6.25 or 12.5 mg three times daily) normalized the supine blood pressure of 35% of these patients acutely. We suggest that in hypertensive patients already taking a diuretic, a lower starting dose of captopril than the recommended 25 mg three times daily may be desirable.

Adult↗
PubMed1973

Micropuncture study of diuretic effects on sodium and calcium reabsorption in the dog nephron.

A close relationship has been observed between the clearance rates of sodium and calcium under a variety of diuretic conditions. The thiazide diuretics act differently in dissociating the renal tubular reabsorption of sodium and calcium. This phenomenon has been further investigated using recollection micropuncture and clearance techniques in a group of 14 dogs subjected to three consecutive experimental phases: expansion to 3% of body weight (BWt) with Ringer's solution, chlorothiazide infusion at 20 mg/kg/h, and furosemide in a prime of 10 mg/kg/ and a 10 mg/kg/h infusion. Diuretic losses were balanced with infusion of equal volumes of Ringer's solution throughout the experiment. Chlorothiazide increased the fractional excretion (FE) of sodium almost threefold while FE(Ca) was not significantly altered. Furosemide increased FE(Na) and FE(Ca) to an approximately equal, and more marked, degree. This dissociation of sodium and calcium reabsorption after chlorothiazide was also evident in the superficial distal tubule, where (tubule fluid/plasma sodium) (TF/P(Na)) increased from 0.32 to 0.49 (P < 0.01) and TF/(ultrafiltrate)UF(Ca) was unchanged (0.35-0.31). Furosemide markedly reduced the transtubular concentration gradient for both sodium (0.86) and calcium (0.94). TF/P(Inul in) decreased progressively from 3.79 to 2.78 to 2.33 in three phases. In the late proximal tubule, chlorothiazide induced a fall of TF/P(Inul in) from 1.57 to 1.44 (P < 0.01), but the ratio TF/UF(Ca): TF/P(Na) was unchanged. Furosemide had no significant proximal effect. It is concluded that acute administration of chlorothiazide reduces sodium reabsorption in the distal hephron, presumably the cortical diluting segment, without affecting calcium reabsorption.

Animals↗
PubMed2001

Diuretics: again the first step in the treatment of most patients with hypertension.

The results and interpretations of the most recent controlled clinical trials on antihypertensive drugs have fuelled the debate about the drug that should be used to begin treatment for hypertension. Every comparison of diuretics with other drugs has shown that the benefits of diuretics are equivalent to, or better than, other options. These findings, together with other practical reasons, such as left ventricular mass reducing effect, easy administration, few side effects and low cost, suggest that diuretics should regain their primacy as the first step in drug management of hypertension.

Journal Article↗
PubMed1999

The distribution of a CRF-like diuretic peptide in the blood-feeding bug Rhodnius prolixus.

The blood-feeding bug Rhodnius prolixus ingests a large blood meal, and this is followed by a rapid diuresis to eliminate excess water and salt. Previous studies have demonstrated that serotonin and an unidentified peptide act as diuretic factors. In other insects, members of the corticotropin-releasing factor (CRF)-related peptide family have been shown to play a role in post-feeding diuresis. Using fluorescence immunohistochemistry and immunogold labelling with antibodies to the Locusta CRF-like diuretic hormone (Locusta-DH) and serotonin, we have mapped the distribution of neurones displaying these phenotypes in R. prolixus. Strong Locusta-DH-like immunoreactivity was found in numerous neurones of the central nervous system (CNS) and, in particular, in medial neurosecretory cells of the brain and in posterior lateral neurosecretory cells of the mesothoracic ganglionic mass (MTGM). Positively stained neurohaemal areas were found associated with the corpus cardiacum (CC) and on abdominal nerves 1 and 2. In addition, Locusta-DH-like immunoreactive nerve processes were found over the posterior midgut and hindgut. Double-labelling studies for Locusta-DH-like and serotonin-like immunoreactivity demonstrated some co-localisation in the CNS; however, no co-localisation was found in the medial neurosecretory cells of the brain, the posterior lateral neurosecretory cells of the MTGM or neurohaemal areas. To confirm the presence of a diuretic factor in the CC and abdominal nerves, extracts were tested in Malpighian tubule secretion assays and cyclic AMP assays. Extracts of the CC and abdominal nerves caused an increase in the rate of secretion and an increase in the level of cyclic AMP in the Malpighian tubules of fifth-instar R. prolixus. The presence of the peptide in neurohaemal terminals of the CC and abdominal nerves that are distinct from serotonin-containing terminals indicates that the peptide is capable of being released into the haemolymph and that this release can be independent of the release of serotonin.

Animals↗
PubMed2001

The Drosophila melanogaster homologue of an insect calcitonin-like diuretic peptide stimulates V-ATPase activity in fruit fly Malpighian tubules.

The Drosophila melanogaster homologue of an insect calcitonin-like diuretic hormone was identified in a BLAST search of the Drosophila genome database. The predicted 31-residue amidated peptide (D. melanogaster DH31; Drome-DH31) was synthesised and tested for activity on fruit fly Malpighian tubules. It increases tubule secretion by approximately 35 % of the response obtained with a myokinin from the housefly Musca domestica (muscakinin; Musdo-K) and has an EC50 of 4.3 nmol x l(-1). The diuretic activities of Drome-DH31 and Musdo-K were additive when tested at threshold and supra-maximal concentrations, which suggests that they target different transport processes. In support of this, Drome-DH31 increased the rate of secretion by tubules held in bathing fluid with a reduced Cl- concentration, whereas Musdo-K did so only in the presence of Drome-DH31. Stimulation with Drome-DH31 increased the lumen-positive transepithelial potential in the main secretory segment of the tubule. This was attributed to activation of an apical electrogenic proton-translocating V-ATPase in principal cells, since it was associated with hyperpolarisation of the apical membrane potential and acidification of secreted urine by 0.25 pH units. Exogenous 8-bromo-cyclic AMP and cyclic GMP increased tubule secretion to the same extent as Drome-DH31 and, when tested together with the diuretic peptide, their activities were not additive. Stimulation with Drome-DH31 resulted in a dose-dependent increase in cyclic AMP production by tubules incubated in saline containing 0.5 mmol x l(-1) 3-isobutyl-1-methylxanthine, whereas cyclic GMP production was unchanged. Taken together, the data are consistent with Drome-DH31 activating an apical membrane V-ATPase via cyclic AMP. Since the K+ concentration of the secreted urine was unchanged, it is likely that Drome-DH31 has an equal effect on K+ and Na+ entry across the basolateral membrane.

1-Methyl-3-isobutylxanthine↗
PubMed1975

The control of diuresis in the tsetse fly Glossina austeni: a preliminary investigation of the diuretic hormone.

The rate of secretion of the Malpighian tubules of Glossina austeni is controlled by a diuretic hormone. This hormone is present in the nervous tissue of the fly together with a degradative enzyme that can be activated by boiling. It is demonstrated that the Malpighian tubules are able to destroy the diuretic hormone; they may therefore participate in the control of diuresis. The diuretic hormone appears to be a heat-stable, non-dialysable, alcohol-soluble molecule, containing amino acid, glucose and sialic acid residues.

Animals↗
PubMed1987

The diuretic effect of furosemide in relation to its disposition in man.

Experiments concerning the diuretic effect and disposition of furosemide were performed in nine healthy male volunteers. During the test period, each of subject was given 50 ml of water every half an hour. Under this experimental condition, interesting phenomena, such as almost identical duration of diuretic effect independent of given dose and the so-called clockwise hysteresis of the concentration-effect curve were observed. These phenomena revealed that the body water regulation system had intervened in the pharmacodynamics of furosemide. Based on experimental results, a model and a new equation are presented, which describe the quantitative relationship of the drug disposition, the diuretic response and the body water regulatory function.

Administration, Oral↗
PubMed1993

[Effects of KW-3635 on the diuretic action of furosemide in rats].

The effects of KW-3635 (sodium (E)-11-[2-(5,6-dimethyl-1-benzimidazolyl) ethylidene]-6,11-dihydrodibenz-[b,e]oxepine-2-carboxylate monohydrate, CAS 127166-41-0), a novel thromboxane A2 (TxA2) receptor antagonist, on furosemide diuresis were examined in rats. After an overnight fast, the rats received either saline or drugs, and 6-hr urine samples were collected. Urine volume, urinary excretion of electrolytes and urine TxB2 were measured. The administration of KW-3635 (10, 30 mg/kg, p.o.) or BM-13505 (10, 30 mg/kg) significantly increased the diuretic effect of furosemide (10 mg/kg, p.o.). Neither drug had any effect on urinary excretion of TxB2. These results demonstrated that the diuretic effect of furosemide was potentiated by TxA2 receptor blockade with KW-3635 or BM-13505. It is suggested that the diuretic effect of furosemide might be modulated by renal production of TxA2 elicited by this drug.

Administration, Oral↗
PubMed1997

Diuretic renography findings in enterovesical fistula.

A 73-year-old male presented with a 2 week history of gross haematuria and faecal material in the urine. Bone scan for cancer work-up showed 99T(cm)-MDP radioactivity accumulation in the transverse and descending colon. A 99T(cm)-DTPA diuretic renogram was arranged to study renal function and to determine the location of the enterovesical fistula. Diuretic renography demonstrated extraurinary tract radioactivity in the sigmoid colon in the early images, extending to the descending and transverse colon in the subsequent dynamic images. A sigmoid colon adenocarcinoma with bladder wall invasion and fistula formation was confirmed at surgical operation. The impressive dynamic diuretic renography study in this patient was helpful in determining the location of the fistula and in planning surgical management.

Adenocarcinoma↗
PubMed1983

Clonidine in the elderly hypertensive. Monotherapy and therapy with a diuretic.

Forty-eight elderly patients with uncomplicated mild essential hypertension entered two drug regimens. In group 1, clonidine monotherapy (n = 15), clonidine was titrated to achieve goal blood pressure (less than 90 mm Hg diastolic) in dosages of 0.05 mg twice daily to 0.2 mg three times daily. Blood pressure decreased without major side effects (p less than 0.001). Three patients required small doses of diuretic after six months of clonidine monotherapy. In group 2, step-care therapy (n = 33), clonidine was added to chlorthalidone, 25 mg daily, for three weeks. Eight patients achieved the goal blood pressure with chlorthalidone, 25 required clonidine (0.1 mg to 0.3 mg twice daily) to achieve blood pressure control. Side effects of clonidine did not require discontinuation of therapy. Retrospective analysis of up to 2 1/2 years of clonidine plus diuretic (n = 51) showed a similar blood pressure reduction. Clonidine can be used effectively with or without a diuretic in the elderly hypertensive.

Aged↗
PubMed1992

Tubular resistance to furosemide contributes to the attenuated diuretic response in nephrotic rats.

A blunted response to loop diuretics frequently occurs in nephrotic syndrome (NS). Observations that nephrotic humans have reduced sodium excretion at normal rates of diuretic excretion have suggested that tubular resistance to the drug may contribute to diuretic resistance. To determine if tubular resistance to furosemide exists in NS, late proximal and early distal tubular micropuncture was performed in rats with puromycin aminonucleoside-induced NS and in control rats after an i.v. bolus dose of furosemide of 1 mg/kg body wt. Absolute and fractional urinary sodium excretions were less (P less than 0.05) in NS rats than in control rats after furosemide. Inulin clearance and total urinary furosemide excretion, however, were not different between groups. Thus, similar to reports in humans, the urinary sodium-to-furosemide excretion ratio was less (P less than 0.05) in NS than in control rats. Single-nephron GFR and chloride delivery to late proximal sites were not different between groups after furosemide. In contrast, absolute and fractional chloride deliveries to early distal sites were less (P less than 0.05) in NS rats after furosemide. Calculated loop chloride reabsorption after furosemide was greater (P less than 0.05) in NS than in control rats when expressed either as percentage of filtered load (39.4 +/- 3.1 versus 28.2 +/- 2.0%) or delivered load (67.9 +/- 4.7 versus 48.3 +/- 3.0%). Loop fluid reabsorption was not different between groups. Thus, loop chloride reabsorption is inhibited to a lesser extent by i.v. furosemide in NS than in normal rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Cochlear vessel permeability to horseradish peroxidase after diuretic administration in the chinchilla.

The permeability of strial vessels to the small protein, HRP, was examined after administration of diuretics to determine if increased vascular permeability is a factor in the development of strial edema as it is in acoustic trauma. Chinchillas were injected with HRP and either ethacrynic acid, a loop-inhibiting diuretic, or mannitol, an osmotic diuretic. There was no increased vascular permeability to HRP. Therefore, unlike the increased vessel permeability of HRP seen after an acoustic insult, increased vessel permeability of HRP is not a factor in the formation of strial edema after either mannitol or ethacrynic acid administration.

Animals↗