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PubMed1977

Comparison of the effect of two groups of diuretics on renin secretion in the anaesthetized dog.

1. The effects of two groups of diuretics on renin secretion have been compared in dogs anaesthetized with pentobarbital. 2. Frusemide, ethacrynic acid and bumetanide cause an immediate rise in renin secretion which is not inhibited either by DL-propranolol or by a bilateral ureterovenous anastomosis which prevents salt and water loss. 3. Clopamide, metolazone and indapamide do not cause an immediate rise in renin secretion. Renin hypersecretion is induced only 1 h after intravenous injection of these diuretics. 4. Renin secretion was studied for 6 h after frusemide injection: the immediate rise was followed by a later increase in renin secretion. This later rise was inhibited by propranolol and by ureterovenous anastomosis. 5. These results allow us to distinguish between a direct renal mechanism responsible for early renin hypersecretion, which appears to be connected with the action of the diuretic on the ascending limb of Henle's loop, and an indirect mechanism responsible for late renin hypersecretion, which appears to be connected with salt and water loss.

Animals↗
PubMed1978

Increased ratio between serum beta- and alpha-lipoproteins during diuretic therapy: an adverse effect?

1. The effect of diuretic therapy on serum lipids and lipoprotein fractions was evaluated in 16 normal or labile hypertensive subjects who received in cross-over fashion chlorthalidone, frusemide or mefruside, each for 4 weeks (group A); and in 13 patients with essential hypertension treated with chlorthalidone for 6 weeks (group B). 2. All three diuretics significantly increased the ratio between serum beta- and alpha-lipoprotein fractions. This was due to an increase of the serum beta-lipoprotein fraction while the alpha-lipoprotein fraction was not changed significantly (group A) or decreased (group B). Serum cholesterol or triglycerides tended to be increased, but mean changes were often not significant. 3. The observed alterations in serum lipoproteins are consistent with the possibility of an increased risk for coronary heart disease which could offset partly the beneficial effects of a lowered blood pressure in diuretic-treated patients with hypertension.

Blood Volume↗
PubMed2003

Analysis of energy metabolism and mechanism of loop diuretics in the thick ascending limb of Henle's loop in dog kidneys.

AIM: The thick ascending limb of Henle's loop (TALH) absorbs up to 40% of filtered NaCl in volume-expanded dogs. To examine if a fraction of this absorption is passive, NaHCO3 absorption and associated NaCl absorption in proximal tubules were inhibited by acetazolamide, a carbonic anhydrase inhibitor. RESULTS: Ouabain, a specific inhibitor of Na,K-ATPase activity, reduced the remaining NaCl absorption and renal oxygen consumption in a ratio DeltaNa/DeltaO2 = 18, as expected for active transport. However, the responses to two loop diuretics were DeltaNa/DeltaO2 = 24 for ethacrynic acid and DeltaNa/DeltaO2 = 30 for bumetanide. Both loop diuretics induced potassium secretion. By superimposing ouabain potassium secretion was stopped and DeltaNa/DeltaO2 = 18 restored. Replacement of half of the circulating NaCl with Na2SO4 gave stop-flow pattern similar to those obtained after ethacrynic acid. CONCLUSIONS: Low entry of some sodium ions thorugh the apical membrane is permitted despite low chloride supply or blockade by loop diuretics of chloride entry by the Na-K-2Cl transporter. Continued Na-K-ATPase activity causes secretion of potassium ions through the apical ion channel, ethacrynic acid being more kaliuretic and less natriuretic than bumetanide. Greater paracellular recycling of sodium ions after bumetanide maintains ionic balance. In contrast, under normal conditions excess entry of chloride by the Na-K-2Cl-transporter leads to paracellular back-diffusion of chloride rather than paracellular absorption of sodium ions, consistent with DeltaNa/DeltaO2 = 18 after ouabain. Thus all NaCl transport along TALH is active in vivo, whereas absorption of other cations, such as lithium, probably is passive.

Absorption↗
PubMed2002

Resistive index: an experimental study of the effects of diuretic stimulation in the unobstructed porcine kidney.

OBJECTIVE: To study the effects of diuretic stimulation with frusemide and mannitol on the renal resistive index (RI) of the undilated unobstructed porcine kidney. MATERIALS AND METHODS: Experiments were carried out on 14 pigs divided into two equal groups (A and B), under general anaesthesia. In all pigs both ureters were catheterized, thereby allowing urine output to be measured on each side separately, and an indwelling catheter in a femoral artery used to continuously measure the systemic blood pressure. Furthermore, in five pigs from each group, right renal blood flow was measured by ultrasonic flow probes placed around the renal arteries. The right kidney RI was measured at baseline and at 5-min intervals after frusemide (group A) and mannitol (group B) stimulation, for 75 min. RESULTS: Frusemide caused significant increases in diuresis (P < 0.001) and renal blood flow (P = 0.009). This was accompanied by a significant decrease in mean arterial pressure (P < 0.001). The RI was unaffected (P = 0.706), with mean values in group A of 0.58-0.65. Mannitol also caused a significant increase in diuresis (P < 0.001) and a subtle but significant decrease in mean arterial pressure (P < 0.001). However, renal blood flow was unaffected by the diuretic (P = 0.820); the mean RI values were unaffected, at 0.61-0.66 (P = 0.375). CONCLUSIONS: These results show that diuretic stimulation with frusemide or mannitol does not affect the RI of the unobstructed undilated porcine kidney, despite significant changes in diuresis, renal blood flow and mean arterial pressure.

Animals↗
PubMed2000

Effect of posture on sodium excretion and diuretic efficacy in nephrotic patients.

It is well known that posture affects natriuresis in cirrhosis and heart failure. This study evaluates the role of posture on spontaneous urinary salt excretion (U(Na)V) and diuretic-induced natriuresis in nephrotic patients with mild renal impairment. U(Na)V and plasma concentrations of the main hormones involved in sodium regulation were evaluated at baseline (Baseline) and after furosemide administration (20 mg intravenously at 8:00 AM [Diuretic]) in seven nephrotic patients with mild renal impairment (creatinine clearance, 68.5 +/- 7.6 mL/min) in either the supine or upright position for 6 hours (from 8:00 AM to 2:00 PM). At baseline, U(Na)V was greater in the supine than upright position (sodium, 51.8 +/- 6.2 versus 38.3 +/- 6.1 mEq/d; P: < 0.01). Similarly, furosemide was more effective in increasing U(Na)V in the supine (sodium, 51.8 +/- 6.2 to 87.4 +/- 9.1 mEq/d; P: < 0.005) than upright position (sodium, 38.3 +/- 6.1 to 59.0 +/- 6.8 mEq/d; P: = not significant). Consequently, body weight decreased in the supine but not the upright position (-0.73 +/- 0.15 versus -0.17 +/- 0.22 kg; P: < 0. 05). Peripheral renin activity (PRA) and plasma aldosterone (Aldo) concentrations were greater in the upright than supine position at both Baseline and Diuretic. A similar pattern was observed for hematocrit, used as an index of plasma volume. In addition, a positive correlation was detected between hematocrit and PRA (r = 0.89; P: < 0.001) in the upright position. Postural changes did not influence plasma concentrations of atrial natriuretic peptide. These data indicate that in nephrotic patients with mild impairment of glomerular filtration rate, the upright position causes a reduction in plasma volume; this hypovolemia activates the renin-Aldo system responsible for sodium retention in unstimulated conditions and a blunted natriuretic response to furosemide.

Aldosterone↗
PubMed2006

Design, synthesis and diuretic activity of some novel 2,4-diamino-6-aryl-7-arylaminopyrimido [4,5-d]pyrimidin-5(6H)-ones.

Synthesis and diuretic activity of some novel 2,4-diamino-6-aryl-7-arylaminopyrimidol4,5-d]pyrimidin-5(6H) -ones were described. The series was designed on the basis of structural similarity between pteridines and pyridopyrimidines. Designed molecules were synthesized by cyclo-condensation of 5-cyano-6-methylmercapto-3-aryl-2-arylaminopyrimidin-4(3H)-one with guanidine. All the compounds were screened for their diuretic activity using triamterene and furosemide as standard drugs. Compounds 2a, 2b, 2d, 2e and 2f were found more potent than triamterene. Compound 2e exhibited diuretic activity comparable to furosemide with greater natriuretic effect. It also exhibited significant antihypertensive activity.

Animals↗
PubMed2001

[Gd-BOPTA enhanced excretory MR urography without administration of diuretics].

PURPOSE: To evaluate the feasibility and clinical utility of Gd-BOPTA enhanced excretory magnetic resonance urography without additional administration of diuretics in correlation with conventional urography. METHOD: 15 preoperative patients with pelvic tumors were examined at 1.5 T using a breath-hold high-resolution 3D-FLASH sequence during first-pass as well as 5, 10, 15 minutes after i.v. injection of 0.05 mmol/kg BW Gd-BOPTA (MultiHance) without administration of diuretics. Post-processed coronal and multiplanar MIP reconstructions were compared to conventional excretory urography with regard to morphologic accuracy, anatomic variability, filling defects, cause and level of obstruction or compression, tumor visibility, and time-effectiveness by two independent radiologists. RESULTS: Visualization of the urinary tract by MRU was comparable to conventional excretory urography in 14 of 15 cases. Caliceal fornices were better delineated on conventional urographies, whereas MRU was considered superior in the assessment of the inferior ureter sections, the urinary bladder and obstructive tumors, whose extents could be clearly marked out. Examination times of both techniques were comparable. CONCLUSION: These first results show that non-diuretic Gd-BOPTA enhanced MRU is comparable to conventional excretory urography for the preoperative diagnosis of pelvic tumors. Further improvements of this technique seem possible by optimization of examination intervals and injection doses.

Adult↗
PubMed1985

Potassium supplementation in hypertensive patients with diuretic-induced hypokalemia.

Changes in potassium balance have been found to have variable effects on the blood pressure of animals, and the administration of potassium supplements has been reported to lower the blood pressure of normokalemic hypertensive patients. To assess the effect of potassium repletion in hypokalemic hypertension, we administered either potassium chloride, 60 mmol per day, or placebo tablets, each for six weeks, in a randomized, double-blind, crossover trial to 16 hypertensive patients who had diuretic-induced hypokalemia and who continued to take a constant amount of diuretic. We selected patients whose control serum potassium levels were below 3.5 mmol per liter. In association with an average rise in the serum potassium concentration of 0.56 mmol per liter, the mean blood pressure fell by an average of 5.5 mm Hg (P = 0.004), with at least a 4 mm Hg fall observed in 9 of the 16 patients. The fall in blood pressure correlated with a fall in plasma renin activity (r = 0.568, P = 0.043) but not with changes in plasma aldosterone levels or other variables. We conclude that short-term potassium supplementation that ameliorates diuretic-induced hypokalemia may induce a significant fall in blood pressure.

Adult↗
PubMed2000

Cockroach diuretic hormones: characterization of a calcitonin-like peptide in insects.

Insect diuretic hormones are crucial for control of water balance. We isolated from the cockroach Diploptera punctata two diuretic hormones (DH), Dippu-DH(31) and Dippu-DH(46), which increase cAMP production and fluid secretion in Malpighian tubules of several insect species. Dippu-DH(31) and -DH(46) contain 31 and 46 amino acids, respectively. Dippu-DH(46) belongs to the corticotropin-releasing factor (CRF)-like insect DH family, whereas Dippu-DH(31) has little sequence similarity to the CRF-like DH, but is similar to the calcitonin family. Dippu-DH(46) and -DH(31) have synergistic effects in D. punctata but have only additive effects in Locusta migratoria. Dippu-DH(31) represents a distinct type of insect DH with actions that differ from those of previously identified insect peptides with diuretic activity.

Amino Acid Sequence↗
PubMed2001

Study on the diuretic activity of Strychnos potatorum Linn. seed extract in albino rats.

Methanol extract of Strychnos potatorum Linn. seeds (SPSE) was evaluated for its diuretic activity in Wistar albino rats. The SPSE was administered at the graded doses of 200, 400, and 600 mg/kg body weight. The parameters which were taken into account during the experimental on each rat were: total urine volume (corrected for water intake during the test period), body weight before and after the experiment, and the concentration of sodium, potassium, and chloride ions in urine. The total urine volumes of the SPSE (600 mg/kg)-treated rats were evaluated nearly two and half fold then compared with the control (saline treated) group. Excretion of cations (sodium and potassium ions) and anions (chloride ions) also increased significantly with respect to the control group. The diuretic effect was comparable with that of the standard drug Furosemide. The increase of cations in the urine on treatment with Strychnospotatorum seed extract (SPSE) was dose-dependent. This effect supports the use of the Strychnos potatorum seeds as a diuretic in folk remedies.

Animals↗
PubMed1982

Unnecessary diuretic therapy in the elderly.

The possible beneficial or adverse effects of long-term diuretic use in the elderly were evaluated in 60 males (mean age 80.0 years) and 17 females (mean age 84.3 years). All subjects were found to have no obvious need for diuretics when initially assessed and were not receiving concurrent digoxin therapy. Residents were randomly allocated to placebo or active groups with stratification for prior hypertension or congestive heart failure (CHF) and they were followed for one year in a double-blind design. Mean BP, heart rate and weight at one year were similar to baseline values in both groups. Six active and two placebo subjects developed CHF and two other placebo subjects had a return of BP to hypertensive levels. Serum creatinine, cholesterol, potassium and BUN were significantly improved at one year in the placebo group. Chronic diuretic use did not alter appreciably the occurrence of CHF or hypertension in this elderly population and may not be necessary.

Aged↗
PubMed1992

Clinical pharmacology of loop diuretics in health and disease.

There are differences in metabolism and excretion of the loop diuretics which extrapolate to differences in pharmacokinetic behaviour in different disease states. For example, furosemide is eliminated in equal portions by renal and non-renal routes; the non-renal route involves primarily glucuronidation. Both renal and non-renal pathways are impaired during renal insufficiency, such that the elimination half-life is prolonged considerably in this disease state. In contrast, there seems to be little change in disposition in patients with liver disease. Bumetanide and torasemide have non-renal elimination pathways via the hepatic cytochrome system. In patients with renal insufficiency these non-renal pathways of elimination are left intact so that there is little prolongation of half-life in such patients. In contrast, in patients with liver disease or with congestive hepatopathy, there is impairment in non-renal elimination so that relatively more drug appears in the urine. With all loop diuretics, response is governed by the amount of drug appearing in the urine. By assessing the relationship between urinary excretion rates of the diuretic and sodium excretion rate, a maximal response which amounts to a fractional excretion of sodium of approximately 20% can be defined. Thus it is possible to define a maximal dose as the amount of drug necessary to attain a fractional excretion of sodium of 20%. Studies in different disease states using escalating doses can thereby use this relationship to define a dose above which little is to be gained in terms of therapeutic efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)

Diuretics↗
PubMed1992

Diuretics and arteriolar resistance and arterial compliance in human hypertension.

Differences exist between short- and long-term haemodynamic effects of diuretics. In the short term, plasma volume depletion is accompanied by increased peripheral vascular resistance and decreased cardiac output. In the long term cardiac output returns toward normal, peripheral resistance falls to below pretreatment values and blood volume remains lower than before therapy. This long-term decrease in volume may contribute to the chronic antihypertensive effects of diuretics. Many studies have reported that arterial compliance is increased after antihypertensive drug administration. However, it is important to known whether such action is a primary pharmacological effect or mediated by the reduction in blood pressure. Two different methods using pulse wave velocity measurements have been applied to determine the pressure-dependence of compliance before and after thiazide administration. In the first method, blood pressure was controlled as a variable by changing transmural pressure of the forearm encased in a rigid plastic tube. In the other method arterial compliance in the brachial artery was evaluated using a simple non-linear arterial model. Both methods demonstrated that the decrease in blood pressure with thiazide therapy was associated with increased arterial compliance. However, by measuring arterial compliance at the same pressure, its isobaric values were found to be unchanged. The implication is that the increase in compliance of the peripheral artery observed with diuretics is due to the decline in blood pressure rather than to a change in the intrinsic properties of the arterial wall.

Arterioles↗
PubMedDate not supplied

Systematic analysis of diuretic doping agents by HPLC screening and GC/MS confirmation.

The simultaneous analysis of diuretic agents by reversed-phase liquid chromatography with a diode-array detector (DAD) was performed by using a gradient elution with acetonitrile and phosphate buffer on a Hypersil-ODS column. For the spiked urine the extraction recovery of solid-phase extraction (SPE) using Sep-Pak C18 cartridge was compared with that of liquid-liquid extraction (LLE) with diethyl ether at various pH. The standard calibration curves were linear from 0.20-20.0 micrograms/mL for all diuretic agents except amiloride, 1.0-20.0 micrograms/mL, and the detection limit was about 0.2 micrograms/mL for 3 mL of urine, except that of amiloride, which was 1.0 micrograms/mL. The confirmation analysis was performed by gas chromatography/mass spectrometry (GC/MS) following methylation. The characteristic mass fragment ions obtained by electron-impact (EI) ionization (70 eV) provided identification of each diuretic agent.

Adult↗
PubMed1989

Hyperparathyroidism, hypertension and loop diuretic medication in renal transplant recipients.

The associations between serum parathyroid hormone (PTH), blood pressure and hypotensive medication were analysed in 282 renal transplant recipients. Among patients with a normal concentration of serum creatinine there was no correlation between serum PTH and blood pressure but in those receiving hypotensive medication serum PTH was appropriately twofold greater than in those not taking hypotensive medication. Analysis revealed that the dominant contribution to this association was a specific association with loop diuretic therapy. When all patients were stratified according to creatinine clearance, serum PTH was always greater in patients receiving loop diuretics but this difference was particularly striking in the patients with the poorest graft function. It is postulated that loop diuretics exacerbate the hyperparathyroidism which complicates renal disease.

Adult↗
PubMed1992

Pseudo-Bartter's syndrome from surreptitious diuretic intake: differential diagnosis with true Bartter's syndrome.

Five patients with pseudo-Bartter's syndrome from surreptitious diuretic abuse were compared with six patients with true Bartter's syndrome, diagnosed as a normotensive, hyperreninaemic, hypokalaemic metabolic alkalosis with normal urine chloride excretion, low CH2O/(CH2O+CCl) ratio during maximal water diuresis and negative urine screen for diuretics. The latter was positive for frusemide in four and for hydrochlorothiazide in the remaining pseudo-Bartter's patients. The two groups of patients did not differ as for plasma Na+, Cl-, K+, HCO3-, renin, and aldosterone, while uric acid and Mg2+ were greater in pseudo-Bartter's patients. Daily and fasting urine Na+, Cl- and K+ excretion were less in pseudo-Bartter's patients; however, there was substantial overlap of values between the two groups. Fractional distal solute reabsorption during maximal water diuresis was low in the six patients with Bartter's syndrome and in two pseudo-Bartter's patients; thus, this parameter could not be taken as a specific diagnostic marker of Bartter's syndrome. Frusemide administration, 40 mg i.v., induced a brisk increase of urine flow (11.7-21.8 ml/min), UOsm (148-186 mOsm/kg H2O) and FENa (14.6-24%) in Bartter's syndrome, but not pseudo-Bartter's patients; in all pseudo-Bartter's patients frusemide-induced changes of UOsm (13-97) and FENa (-0.5 to 10.2) were markedly less than in Bartter's syndrome patients. Frusemide resistance in pseudo-Bartter's patients was most probably related to diuretic-induced ECF volume contraction and increased proximal tubule solute reabsorption; in fact fractional lithium clearance (FELi, a marker of post-proximal solute delivery) was low in pseudo-Bartter's, but not in Bartter's syndrome patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Bed rest and increased diuretic treatment in chronic congestive heart failure.

To elucidate the effect of bed rest used as an adjunct to increased diuretic treatment, twelve patients with chronic congestive heart failure (CHF) had a 50% increase in loop diuretic dosage and were allocated to either continuous bed rest or bed rest during nights only. The 24-hour bed rest group reduced their weight significantly (mean +/- SEM: 2.00 +/- 0.79 kg, P less than 0.001), whereas the night bed rest group had no significant weight reduction (1.10 +/- 0.37 kg, 0.1 less than P less than 0.2) during three days of observation. Furthermore, the 24-hour bed rest group had a significantly increased diuresis (P less than 0.05) during the first day of the study and a tendency towards increased natriuresis. The cumulated diuresis for the two groups (24-hour bed rest versus night bed rest) during the three days of study were 7773 +/- 700 ml and 5861 +/- 909 ml (0.05 less than P less than 0.1), respectively. Plasma concentrations of adrenaline, noradrenaline, renin and aldosterone were increased, as measured in the supine position. No significant differences were found between the two groups. Plasma concentrations of antidiuretic hormone were within normal limits. In conclusion, continuous bed rest is a reasonable adjunct to diuretic treatment in patients with CHF.

Adult↗
PubMed1990

An assault on old friends: thiazide diuretics under siege.

The adverse biochemical effects of thiazide use are of uncertain clinical significance. Thiazides raise LDL cholesterol only slightly in long-term studies and do not decrease HDL cholesterol. The evidence linking thiazide-induced hypokalemia with arrhythmias and sudden death is tenuous at best. Thiazide diuretics cause glucose intolerance, but no strong evidence has been advanced to suggest that this is dangerous. Because these effects are probably related to hypokalemia, a randomized trial comparing the effects of thiazides with thiazides plus a potassium-sparing diuretic on LDL cholesterol, ectopy on 48 hour ambulatory cardiac monitoring, fasting glucose and insulin, and post-glucose tolerance glucose and insulin would be of interest. The most compelling reason for continuing to use thiazides is that they have been shown in long-term randomized studies to reduce cardiovascular risk. Beta-blockers are the only other class of anti-hypertensive agent for which this claim can be made. The importance of long-term clinical trials in assessing the efficacy and toxicity of therapeutic agents is illustrated by the study that found clofibrate reduced cholesterol levels and coronary disease but increased total mortality. This finding remained undetected until a large randomized long-term trial was completed. Thiazide diuretics have not reduced the rate of coronary disease to the degree expected from epidemiologic studies, but the short length of the randomized trials may be responsible. It is not clear that other anti-hypertensive agents will be superior. Thiazides are less expensive than other anti-hypertensive agents being touted as metabolically safer; the cost issue is not a trivial matter.(ABSTRACT TRUNCATED AT 250 WORDS)

Benzothiadiazines↗