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PubMed1982

Do all diuretics have equal hypotensive efficacy?

An open parallel study was carried out in general practice on 70 patients with uncomplicated mild to moderate hypertension to compare the hypotensive efficacy of hydrochlorothiazide/amiloride with that of cyclopenthiazide/potassium. After a 2-week baseline period on placebo, patients were allocated at random to receive treatment with one or other of the diuretics starting with 1 tablet per day and increasing up to a maximum of 4 tablets per day or until their supine diastolic blood pressure was 90 mmHg or less. They were then continued at their optimum dose for a further 4 weeks. Analysis of the results from 62 patients showed that the hydrochlorothiazide/amiloride preparation produced both a greater decrease and better control of blood pressure in a greater percentage of patients that did the comparison diuretic. In addition, the beneficial effects were attained with fewer tablets, of importance for patient compliance.

Adult↗
PubMed2003

Countrywide computer alerts to community physicians improve potassium testing in patients receiving diuretics.

More than 20% of approximately 35,000 patients filling a diuretic prescription had no potassium blood test recorded within the previous year. A laboratory reporting system used throughout Israel by Maccabi Healthcare Services physicians was modified to provide physician alerts regarding potassium testing. The physicians were experienced users of a computerized medical record (CMR) that provided online laboratory test results. A nightly batch file checked pharmacy diuretic purchases against the patient's potassium blood test status. On-screen computer-generated reminders were sent to physicians of patients lacking a recent potassium test. Reminders to clinicians increased potassium testing by 9.8% (p < 0.001). Physician age and gender played a small part in predicting compliance to the alert, but specialty and practice size did not. The time delay between the date a reminder was sent and the potassium test date decreased steadily during the intervention. The success of this reminder system encourages expansion to include more drug-laboratory interactions. Furthermore, direct alerts to patients at multiple organization/patient contact points are planned.

Ambulatory Care Information Systems↗
PubMed1994

Malabsorption in infants with congenital heart disease under diuretic treatment.

Intestinal absorption and its relationship to increased total body water was studied in seven infants with congenital heart disease receiving regular diuretics due to congestive heart failure. All infants and six age-matched healthy controls were studied for a 3-d period during which time all food intake was recorded, stools were collected, and total body water content (TBW) and extracellular water were measured. All the anthropometric measurements were lower in the infants with congenital heart disease compared with healthy controls. Energy and fat excretion in the stools were significantly increased in the group of patients, but when expressed as a percentage of daily caloric intake or as a percentage of the specific intake (e.g. fat excretion/fat intake x 100), no statistical differences were found. TBW as a percentage of body weight was increased in our patients compared with our controls (84.95 +/- 5.82% versus 68.65 +/- 4.60%; p = 0.01) and so was extracellular water as a percentage of predicted (200.0 +/- 18.6% versus 100.9 +/- 7.2%; p = 0.001). A positive correlation was found between energy and fat excretion as a percentage of the intake and TBW as a percentage of predicted; energy and fat malabsorption did not exceed 8% in the patients with the highest body water content (120% of predicted). It is concluded that malabsorption is not a significant factor in failure to thrive of patients with congenital heart disease who are receiving regular diuretics. Based on the significant negative correlation between excess body water and fat and calorie absorption, however, it is suggested to monitor TBW in patients who fail to gain weight.

Body Water↗
PubMed1995

Acute hyperoxic injury attenuates the relaxing effects of "loop" diuretics and salbutamol on large airways of newborn guinea pigs.

We have previously found an age-dependent relaxing effect of furosemide in normal fetal, newborn, and adult guinea pig airways with fetal trachea exhibiting the greatest relaxation and adult tissue the least. This study was designed to expand upon this finding by determining if in vivo hyperoxic exposure would influence in vitro airway relaxation mediated by the loop diuretics, furosemide and ethacrynic acid, and the beta 2-adrenoceptor agonist, salbutamol. Newborn guinea pigs were raised in > 95% FiO2 until ill; controls in room air. Isometric relaxation to 3 x 10(-5) M furosemide, 3 x 10(-6) M ethacrynic acid, or 10(-8)-10(-6) M salbutamol was recorded in 3 x 10(-6) M histamine-constricted airway rings. Ethacrynic acid, like furosemide, relaxed newborn guinea pig airways. Hyperoxia did not alter the contractile effect of 3 x 10(-6) M histamine but did significantly decrease the relaxing effect of furosemide, ethacrynic acid, and salbutamol. Loop diuretic mediated airway relaxation was accentuated in HEPES buffer when compared with Krebs, whereas salbutamol-mediated relaxation was unaffected. These results suggest that hyperoxia nonspecifically decreases airway responsiveness to the relaxing agents studied.

Albuterol↗
PubMed1993

A comparison of the effects of two putative diuretic hormones from Locusta migratoria on isolated locust malpighian tubules.

Previous work has shown that a peptide related to arginine vasopressin is present in the suboesophageal ganglion of the locust, Locusta migratoria. This peptide was determined to be an anti-parallel dimer of the nonapeptide Cys-Leu-Ile-Thr-Asn-Cys-Pro-Arg-Gly-NH2 and was reported to stimulate cyclic AMP production and fluid secretion in a combined Malpighian tubules and midgut preparation from locusts. For these reasons the peptide has been called the arginine-vasopressin-like insect diuretic hormone (AVP-like IDH). Recently, a second diuretic peptide (Locusta-DP), which is related to corticotropin releasing factor, has been identified: this is a potent stimulant of fluid secretion and cyclic AMP production by isolated locust tubules. Because water balance in insects is likely to be controlled by a cocktail of hormones acting on both Malpighian tubules and hindgut, this study directly compares the activity of these two peptides in fluid secretion and cyclic AMP production bioassays on one target organ, the isolated Malpighian tubule of Locusta migratoria. Locusta-DP was synthesised directly, whereas the dimeric AVP-like IDH was obtained by oxidation of a synthetic nonapeptide monomer. Products were separated by RP-HPLC and their structures unequivocally confirmed by enzymatic digestion, sequence analysis and electrospray mass spectrometry. We show that Locusta-DP causes strong stimulation of fluid secretion and cyclic AMP production, whereas the AVP-like IDH has no effect in either assay. These findings are discussed in the light of recent work on the anatomy and physiology of the vasopressin-like immunoreactive (VPLI) neurones in the suboesophageal ganglion of Locusta migratoria, the proposed source of the AVP-like peptide.

Amino Acid Sequence↗
PubMed2002

The Dh gene of Drosophila melanogaster encodes a diuretic peptide that acts through cyclic AMP.

Dh, the gene that encodes a CRF-like peptide in Drosophila melanogaster, is described. The product of this gene is a 44-amino-acid peptide (Drome-DH(44)) with a sequence almost identical to the Musca domestica and Stomoxys calcitrans diuretic hormones. There are no other similar peptides encoded within the known Drosophila genomic sequence. Functional studies showed that the deduced peptide stimulated fluid production, and that this effect was mediated by cyclic AMP in principal cells only: there was no effect on the levels of either cyclic GMP or intracellular calcium. Stimulation also elevated levels of cyclic AMP (but not cyclic GMP) phosphodiesterase, a new mode of action for this class of hormone. The transcript was localised by in situ hybridisation, and the peptide by immunocytochemistry, to two groups of three neurones in the pars intercerebralis within the brain. These cells also express receptors for leucokinin, another major diuretic peptide, implying that the cells may be important in homeostatic regulation.

Amino Acid Sequence↗
PubMed2002

Antagonistic control of fluid secretion by the Malpighian tubules of Tenebrio molitor: effects of diuretic and antidiuretic peptides and their second messengers.

Fluid secretion by insect Malpighian tubules is controlled by haemolymph-borne factors. The mealworm Tenebrio molitor provides the first known example of antagonistic interactions between endogenous neuropeptides acting on Malpighian tubules. The two corticotropin-releasing-factor (CRF)-related diuretic peptides previously isolated from Tenebrio molitor, Tenmo-DH(37) and Tenmo-DH(47), were found to stimulate Tenebrio molitor tubules in vitro in a dose-dependent manner with EC(50) values of 0.12 nmol l(-1) and 26 nmol l(-1) respectively. However, no synergistic or additive effect was observed when these two peptides were tested simultaneously. We then investigated antagonism between second messengers: dose-response curves were constructed for stimulation of Tenebrio molitor tubules by cyclic AMP and their inhibition by cyclic GMP. When both cyclic nucleotides were included in the bathing Ringer, the stimulatory effect of cyclic AMP was neutralised by cyclic GMP. Similarly, the stimulatory effect of Tenmo-DH(37) was reversed on addition of an antidiuretic peptide (Tenmo-ADF), which was recently isolated from Tenebrio molitor and acts via cyclic GMP. The cardioacceleratory peptide CAP(2b), originally isolated from Manduca sexta, also increases intracellular cyclic GMP levels and inhibited fluid secretion by Tenebrio molitor tubules, with an EC(50) value of 85 nmol l(-1). This inhibitory effect was reversed by Tenmo-DH(37). Endogenous diuretic and antidiuretic peptides, effective at low concentrations and acting via antagonistic second messengers, have the potential for fine control of secretion rates in the Malpighian tubules of Tenebrio molitor.

Age Factors↗
PubMed1994

Diuretic effects of KW-3902, a novel adenosine A1-receptor antagonist, in anesthetized dogs.

The effects of intravenous infusion of KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine), a novel adenosine A1-receptor antagonist, on urine volume, urinary excretion of electrolytes and renal hemodynamics were examined in anesthetized dogs. KW-3902 at 10 and 30 micrograms/kg/min for 20 min inhibited the decline of renal blood flow induced by intrarenal arterial injection of adenosine (0.5-2.0 micrograms). KW-3902 at these doses produced significant increases in urine volume and sodium excretion with little change in potassium excretion. The diuretic effect of KW-3902 at 30 micrograms/kg/min for 20 min continued for longer than 1 h even after discontinuation of the KW-3902 infusion. KW-3902 did not affect creatinine clearance, renal blood flow, arterial blood pressure or heart rate. Furosemide at 10 micrograms/kg/min for 20 min brought about significant increases in urine volume and excretion of sodium and potassium. The diuresis and saliuresis induced by furosemide continued for only 40 min after discontinuation of the drug infusion. Trichlormethiazide at 3 micrograms/kg/min for 20 min also provoked increases in urine volume and sodium excretion, but did not affect potassium excretion. The diuretic and natriuretic effect of trichlormethiazide gradually disappeared after discontinuation of the drug infusion. The present study in anesthetized dogs suggests that KW-3902, an adenosine A1-receptor antagonist, produces diuresis and natriuresis but not kaliuresis and that the diuresis and natriuresis are caused in large part by the inhibition of sodium reabsorption at tubular sites.

Anesthesia↗
PubMed1999

Bioavailability and diuretic effect after administration of retarded capsules of bumetanide in human subjects.

Retarded capsules containing 1 mg bumetanide (BN) were prepared and their in vivo absorption and diuretic effect after oral administration in human subjects were studied. For comparison, commercially available tablets of BN (rapid effect) were administered orally. The mean value of the area under the plasma concentration time curve (AUC) after administration of retarded capsules was about one half that of the tablets. The mean maximum plasma concentration (Cmax) and the mean maximum urinary excretion rate of BN after administration of retarded capsules were also about one half compared to those of the tablets. Cumulative urinary volumes for 24 h, however, were not significantly different between retarded capsules and tablets. Peak times for the urinary excretion rate of BN, urine flow rate and the Cmax after administration of retarded capsules were significantly delayed compared to those of tablets. Clockwise hysteresis relationships between the urine flow rate and plasma concentration or urinary excretion rate of BN were observed after administration of retarded capsules. From these studies, retarded capsules of BN possessed a mild diuresis and its diuretic effect was maintained for a few hours after administration.

Administration, Oral↗
PubMed2004

An anti-aldosteronic diuretic component (drain dampness) in Polyporus sclerotium.

Polyporus Sclerotium botanically from the Polyporus umbellatus (PERS.) FRIES, was traditionally used for the purpose of promoting diuresis. The present study investigated the diuretic effect of ergosta-4,6,8(14),22-tetraen-3-one (ergone) which is a maker component according to the chemical assay for its quality standardization. It resulted in a reversion to ordinary value of the urinary ratio of Na/K in deoxycoricosterone acetate (DOCA)-treated and adrenalectomized rats, although it had no this effect on the Na or K contents as well as Na/K value both in normal rats and in adrenalectomized rats without DOCA. These data indicate that ergone possesses an anti-aldosteronic diuretic effect. Moreover, it was identified in the blood and bile of rats after its administration to the gastrointestinal tract. The above results demonstrate that it is an active component of Polyporus Sclerotium.

Animals↗
PubMed1990

Studies on uricosuric diuretics. I. Syntheses and activities of xanthonyloxyacetic acids and dihydrofuroxanthone-2-carboxylic acids.

A series of substituted xanthonyloxyacetic acids (5 and 6), 1,2-dihydrofuro[2,3-c]xanthone-2-carboxylic acids (7) and 2,3-dihydrofuro[3,2-b]xanthone-2-carboxylic acids (8) were synthesized and tested for diuretic and uricosuric activities in rats. Most of the xanthon-3-yloxyacetic acids (5) and 7 showed potent diuretic activities, while 8 had lower activities. Uricosuric activities were found in 5c, 5f, 5k, 5m, 5o, 5p, 5r, 7m, 7p and 8q.

Animals↗
PubMed1992

Studies on uricosuric diuretics. III. Substituted 1,3-dioxolo[4,5-f]-1,2-benzisoxazole-6-carboxylic acids and 1,3-dioxolo[4,5-g]-1,2-benzisoxazole-7-carboxylic acids.

A series of substituted 1,3-dioxolo[4,5-f]-1,2-benzisoxazole-6-carboxylic acids 13 and 1,3-dioxolo[4,5-g]-1,2-benzisoxazole-7-carboxylic acids 14 were synthesized and evaluated for diuretic and uricosuric activities in rats. Most of the benzisoxazole derivatives 13 and 14 showed potent diuretic activities. Moderate uricosuric activities were also found in 14a, 14b, and 14f.

Animals↗
PubMed1979

Diuretic action of metolazone in dogs.

Metolazone, the sulfonamide diuretic was investigated to determine the sites of action. We used a radioactive microsphere, clearance and stop-flow method in anesthetized dogs. Urine flow and urinary excretion of sodium and potassium were increased at 5--60 min when metolazone was given intravenously at doses of 0.2--5.0 mg/kg, while total renal blood flow, distribution of cortical renal blood flow and GFR did not change. The urinary excretion rate of sodium to potassium (Na/K) increased from 5.69 +/- 0.82 to 8.07 +/- 0.76 in a dose of 1.0 mg/kg, i.v. Osmolar clearance and free water reabsorption increased almost proportionally, indicating that metolazone has little effect on the medullary portion of the ascending limb of Henle and may have a proximal site of action. In stop-flow experiments, a significantly raised U/PNa/U/Pcreatinine was observed at the dip situated distally to the ascending limb of Henle. These findings indicate that the diuretic action of metolazone may be due to the inhibition of sodium reabsorption in the distal nephron segments, in addition to the absence of modification of the cortical regional blood flow.

Animals↗
PubMed1983

Effects of uricosuric drugs and diuretics on uric acid excretion in oxonate-treated rats.

A practical procedure for evaluating uricosuric agents was demonstrated using clearance experiments with potassium oxonate-treated rats. The fractional excretion value of uric acid showed a reabsorptive net flux of uric acid in the renal tubules of the animal, though the value was obviously higher than those of primates such as men, chimpanzees and cebus monkeys. However, the rats responded well to uricosuric drugs and diuretics. Probenecid and uricosuric diuretics such as tienilic acid induced hyperuricosuria due to the increase of fractional excretion of uric acid and/or the increase of the filtered amount of uric acid with the rise of plasma uric acid. On the other hand, furosemide had no effect on uric acid excretion at a low dose with moderate diuresis, while a higher dose decreased the fractional excretion of uric acid with elevation of plasma uric acid. Benzothiazides were also uricosuric at the lower doses, but the high dose, as in the case of the so-called uricosuric drugs, had no effect on the uric acid excretion and plasma uric acid level. Thus, oxonate-treated rats were useful for evaluating drug effects on uric acid excretion.

Animals↗
PubMed1993

Beneficial effect of a novel diuretic, M17055, on blood pressure and cardiovascular hypertrophy in spontaneously hypertensive rats.

We investigated the effects of a novel diuretic, M17055, on blood pressure and cardiovascular hypertrophy in spontaneously hypertensive rats (SHR). M17055 was orally administered once a day for 24 consecutive days to 14-week-old male SHR. M17055 at doses of 1.25, 2.5 and 5 mg/kg/day exerted a dose-related diuretic and antihypertensive effect during the treatment. The weight of the left ventricle normalized by body weight on the following day of the last dosage was significantly (P < 0.01) reduced by M17055 at doses of 2.5 and 5 mg/kg/day in a dose-dependent manner. The effect of M17055 on cardiac hypertrophy was more potent (P < 0.01) than that of captopril, when the comparison was performed at the doses of M17055 and captopril inducing the same extent of blood-pressure decrement. Vascular hypertrophy was evaluated by the media/lumen ratio (M/L) in the thoracic aorta and the first branch of the superior mesenteric artery. In the aorta, M/L was slightly, but not significantly, decreased by M17055 at doses of 2.5 and 5 mg/kg/day, whereas it was decreased significantly (P < 0.01) by captopril. In the mesenteric artery, the ratio was significantly (P < 0.05) reduced by M17055 at a dose of 5 mg/kg/day. These results suggest that M17055 possesses beneficial properties for the clinical treatment of hypertension.

Animals↗
PubMed2004

The diuretic effect of Sairei-to is mediated by nitric oxide production in pentobarbital-anesthetized rats.

Sairei-to (TJ-114), a Japanese traditional medicine, has been used clinically for the treatment of various edematous disorders. The inhibitory effect on edema may be dependent on the diuretic response to TJ-114. This study was conducted to clarify the mechanism of diuresis. Pentobarbital-anesthetized rats were infused with a saline solution intravenously (0.4 mL/30 min). Urine was collected through a bladder cannula for 30 min. Intraduodenal administration of TJ-114 (0.5 - 1.5 g/kg) resulted in a dose-dependent increase of urine volume with insignificant urinary sodium excretion and significant urea excretion, but no effect on mean arterial blood pressure. Furthermore, TJ-114 significantly increased urinary levels of NO(2) + NO(3). In addition, intraperitoneal pre-treatment with 6 mg/kg of N(G)-nitro-L-arginine methyl ester inhibited the increase in urine volume, urinary urea excretion, and urinary levels of NO(2) + NO(3) in the rats treated with TJ-114. These results suggest that TJ-114 induces a diuretic response via production of NO.

Adjuvants, Anesthesia↗
PubMed2000

Effect of long-term treatment with antihypertensive drugs on quality of life of elderly patients with hypertension: a double-blind comparative study between a calcium antagonist and a diuretic. NICS-EH Study Group. National Intervention Cooperative Study in Elderly Hypertensives.

We investigated the effect of long-term treatment with a calcium antagonist (nicardipine hydrochloride retard tablet) and a diuretic (trichlormethiazide) on quality of life (QOL) in elderly hypertensives in a multicenter, randomized, double-blind, comparative study (National Intervention Cooperative Study in Elderly Hypertensives Study Group). The percentage of patients who experienced side effects was 17.2% in the nicardipine group and 18.1% in the trichlormethiazide group and 2.9% and 4.3% of participants, respectively, withdrew due to those side effects. These results suggested that nicardipine was tolerated slightly better than trichlormethiazide. There were no significant differences between the two groups in terms of total QOL score or in degree of change (delta score) before and after calcium antagonist or diuretic administration. Lower score was seen in 3 categories (general symptoms, sleep scale, and sexual function) in the trichlormethiazide group (p< 0.05) and in one category (cognitive function) in the nicardipine group, but there was no significant difference in delta score in any of the individual items. In conclusion, the two anti-hypertensive agents had nearly equivalent effects on QOL in the long-term treatment of hypertension in the elderly and that neither resulted in a deterioration in QOL.

Aged↗
PubMed2005

Diuretic medication therapy use and low thiamin intake in homebound older adults.

Diuretic therapy (DT) plays a major role in disease management. However, one issue of concern in nutritionally vulnerable elders is that diuretic therapy also increases thiamin excretion, and little attention has been paid to the linkage between DT use and dietary intake of thiamin in this older population. The purpose of this study was to assess the relationship between DT use and dietary intake of thiamin in a randomly recruited sample of 342 homebound older adults. Baseline data, including three 24-hour recalls, were used to identify thiamin intake from food (15% < EAR and 33% < RDA), DT use (49%), and meal pattern (18% not regularly eating breakfast). Independent of sociodemographic and meal pattern variables, DT users (relative to non-users) were at increased odds for dietary thiamin intake < RDA (OR = 2.3) and < EAR (OR = 4.2). Considering the importance of home-delivered meals as a primary source of food assistance to homebound elders and that thiamin deficiency may exacerbate health problems, the results of this study suggest the need to include information on DT use as an integral component of program assessment for the targeting and monitoring of strategies to alleviate the risk for deficiency.

Aged↗