Chronic Diuretic Treatment Research Articles

Evaluation of whole blood thiamine pyrophosphate concentrations in critically ill patients receiving chronic diuretic therapy prior to admission to Turkish intensive care units: A pragmatic, multicenter, prospective study

Background/ObjectivesThiamine plays a pivotal role in energy metabolism. The aim of the study was to determine serial whole blood TPP concentrations in critically ill patients receiving chronic diuretic treatment before ICU admission and to correlate TPP levels with clinically determined serum phosphorus concentrations. Subjects/MethodsThis observational study was performed in 15 medical ICUs. Serial whole blood TPP concentrations were measured by HPLC at baseline and at days 2, 5 and 10 after ICU admission. ResultsA total of 221 participants were included. Of these, 18% demonstrated low TPP concentrations upon admission to the ICU, while 26% of participants demonstrated low levels at some point during the 10-day study period. Hypophosphatemia was detected in 30% of participants at some point during the 10-day period of observation. TPP levels were significantly and positively correlated with serum phosphorus levels at each time point (P < 0.05 for all). ConclusionsOur results show that 18% of these critically ill patients exhibited low whole blood TPP concentrations on ICU admission and 26% had low levels during the initial 10 ICU days, respectively. The modest correlation between TPP and phosphorus concentrations suggests a possible association due to a refeeding effect in ICU patients requiring chronic diuretic therapy.

P246 URINARY SODIUM–GUIDED I.V. DIURETIC THERAPY IN ACUTE HEART FAILURE: APPLICATION OF THE YALE DIURETIC PROTOCOL IN A REAL–WORLD ITALIAN SETTING

Abstract Background Loop diuretics are the cornerstone of acutely decompensated heart failure (ADHF) treatment, but evidences on doses and administration modalities are still lacking. Veena S. et al have recently validated the Natriuretic Response Prediction Equation and applied it with the Yale Diuretic Protocol (YDP) in a clinical implementation cohort demonstrating its safety. Objectives Our purpose is to test the applicability and safety of YDP for titration of diuretic therapy in a real–world in–hospital setting, as compared to standard diuretic therapy. METHODS From 15th September 2021 patients hospitalized with ADHF, almost one sign of congestion and need of i.v. diuretics were enrolled. Patients with active bleeding, hematocrit &amp;lt; 21%, or on dialysis were excluded. Patients were treated with i.v. diuretic therapy guided by urinary sodium (YDP–group) or by weight changes and urinary output (control group) based on logistic in–hospital reasons. Results Thirty patients were included. Median age was 76.4 [IQR 68.3; 82.7] years old; median EF and glomerular filtration rate were 40% [IQR 30; 55] and 57.2 ml/min/m2 [IQR 44.9; 79.9], respectively. Nineteen (63.3%) patients were on chronic loop diuretic treatment. Ten (33.3%) patients were treated according to YDP. Main results are shown in the Table attached. YDP patients were younger (p = 0.02) and received shorter treatment with i.v. diuretics (YDP 36 [IQR 27; 48] hours, controls 48 [IQRS 38; 88] hours; p = 0.03). No differences in terms of total diuresis, weight loss at the end of i.v. diuretic therapy and length of hospitalization were shown. YDP patients experienced significant lower increase in creatinine during i.v. diuretic therapy (p = 0.02). The incidence of adverse events was comparable between groups, with equal hypotension rate (10%), and similar plasma levels of electrolytes at the end of i.v. diuretic therapy; YDP patients required less potassium supplementation. Reasons for i.v. diuretic therapy suspension were comparable between groups; 7 (70%) YDP patients concluded i.v. diuretic therapy for satisfactory decongestion, while only one patient because of hypotension and none because of worsening of renal function. Conclusion In our reality the YDP appeared to be applicable, safe and comparable to the standard i.v. diuretic therapy in terms of in–hospital outcomes. These preliminary results need to be confirmed in a larger cohort and longer term outcomes still need to be explored.

Diuretic response and effects of diuretic omission in ambulatory heart failure patients on chronic low-dose loop diuretic therapy.

To study loop diuretic response and effect of loop diuretic omission in ambulatory heart failure (HF) patients on chronic low-dose loop diuretics. Urine collections were performed on two consecutive days in 40 ambulatory HF patients with 40-80 mg furosemide (day 1 with loop diuretic; day 2 without loop diuretic). Three phases were collected each day: (i) first 6h; (ii) rest of the day; and (iii) night. On the day of loop diuretic intake, the total natriuresis was 125.9 (86.9-155.0) mmol/24 h and urine output was 1650 (1380-2025) mL/24 h. There was a clear loop diuretic response with a natriuresis of 9.4 (6.7-15.9) mmol/h and a urine output of 117 (83-167) mL/h during the first 6h, followed by a significant drop in natriuresis and urine output during the rest of the day [2.6 (1.8-4.8) mmol/h and 55 (33-71) mL/h] and night [2.2 (1.6-3.5) mmol/h and 44 (34-73) mL/h]. On day 2, after loop diuretic omission, the natriuresis and urine output remained similarly low the entire day, resulting in a 50% reduction in natriuresis [55.1 (33.5-77.7) mmol/24 h; P < 0.001] and a 31% reduction in urine output [1035 (875-1425) mL/24 h; P < 0.001] compared with the day of loop diuretic intake. Patients with HF on chronic loop diuretic treatment still have a clear diuretic response phase, while loop diuretic omission leads to a significant drop in natriuresis and urine output, arguing against routine cessation of low-dose loop diuretics.

Benfothiamine Administration in Patients with Dilated Cardiomyopathy and Advanced Heart Failure with Chronic Diuretic Treatment

Benfothiamine Administration in Patients with Dilated Cardiomyopathy and Advanced Heart Failure with Chronic Diuretic Treatment

Hyponatremia in patients hospitalized with heart failure: a condition often overlooked in low-income settings.

BackgroundHyponatremia is a common electrolyte abnormality in patients with heart failure (HF). It is independently associated with increased short-term and long-term morbidity and mortality. The main objective of this study was to assess patterns of hyponatremia and its association with discharge outcomes in patients with HF admitted to a teaching hospital in Ethiopia.Patients and methodsThis is a descriptive, prospective, hospital-based cohort study of patients with HF admitted to Jimma University Hospital, Ethiopia, between November 1, 2013 and July 31, 2014. A structured questionnaire was used to collect information on sociodemographic characteristics, clinical profile at admission, and outcomes at discharge. Plasma sodium concentration was analyzed at admission for all patients. The relationship between hyponatremia at admission and in-hospital mortality, as well as length of hospital stay, was assessed using both bivariate analysis and multivariable logistic regressions. The level of statistical significance was set at P<0.05.ResultsOf 152 participants admitted with HF, 44 (28.9%) had hyponatremia, which is defined as serum sodium level <135 mmol/L. Patients on salt restriction, on chronic diuretic treatment (furosemide and spironolactone), and with impaired renal function at admission were found to be highly affected. Hyponatremia was found to be associated with increased in-hospital mortality (P=0.008) and longer hospital stay (16.6 vs 12 days, P<0.001). Patients with hyponatremia also had lower blood pressure and poor functional status at discharge.ConclusionThis study demonstrates that hyponatremia is highly prevalent in patients hospitalized with HF and is associated with increased in-hospital mortality and longer hospital stay. Thus, great emphasis should be given to identify high-risk patients, and prevention and early detection of hyponatremia to prevent its deleterious effects. Large-scale national studies are also needed to complement our findings.

Impact of chronic diuretic treatment on glucose homeostasis.

BackgroundThe use of diuretics for hypertension has been associated with unfavorable changes in cardiovascular risk factors, such as uric acid and glucose tolerance, though the findings in the literature are contradictory.MethodsThis study investigated whether diuretic use is associated with markers of metabolic and cardiovascular risk, such as insulin-resistance and uric acid, in a cohort of adults without known diabetes and/or atherosclerotic cardiovascular disease. Nine hundred sixty-nine randomly selected participants answered a questionnaire on clinical history and dietary habits. Laboratory blood measurements were obtained in 507 participants.ResultsPreviously undiagnosed type 2 diabetes was recognized in 4.2% of participants who were on diuretics (n = 71), and in 2% of those who were not (n = 890; P = 0.53). Pre-diabetes was diagnosed in 38% of patients who were on diuretics, and in 17.4% (P < 0.001) of those who were not. Multivariate analysis showed that insulin-resistance (HOMA-IR) was associated with the use of diuretics (P = 0.002) independent of other well-known predisposing factors, such as diet, physical activity, body mass index, and waist circumference. The use of diuretics was also independently associated with fasting plasma glucose concentrations (P = 0.001) and uric acid concentrations (P = 0.01).ConclusionsThe use of diuretics is associated with insulin-resistance and serum uric acid levels and may contribute to abnormal glucose tolerance.

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.

Matching salt intake to physiological need in rats using foraging protocols

Several studies of the quantitative relationship between sodium need and sodium intake in rats are reviewed. Using acute diuretic treatment 24 h beforehand, intake matches need fairly accurately when intake is spread out in time by using a hypotonic solution of NaCl. In contrast, using a hypertonic solution, intake is typically double the need. Using the same diuretic treatment, although the natriuresis occurs within approximately 1 h, the appetite appears only slowly over 24 h. Increased plasma levels of aldosterone parallel the increased intake; however, treatment with metyrapone blocks the rise in aldosterone but has no effect on appetite. Satiation of sodium appetite was studied in rats using sodium loss induced by chronic diuretic treatment and daily salt consumption sessions. When a simulated foraging cost was imposed on NaCl access in the form of a progressive ratio lever press task, rats showed satiation for NaCl (break point) after consuming an amount close to their estimated deficit. The chronic diuretic regimen produced hypovolemia and large increases in plasma aldosterone concentration and renin activity. These parameters were reversed to or toward non-depleted control values at the time of behavioral satiation in the progressive ratio protocol. Satiation mechanisms for sodium appetite thus do appear to exist. However, they do not operate quantitatively when concentrated salt is available at no effort, but instead allow overconsumption. There are reasons to believe that such a bias toward overconsumption may have been beneficial over evolutionary time, but such biasing for salt and other commodities is maladaptive in a resource-rich environment.

Matching salt intake to physiological need in rats using foraging protocols

Several studies of the quantitative relationship between sodium need and sodium intake in rats are reviewed. Using acute diuretic treatment 24 h beforehand, intake matches need fairly accurately when intake is spread out in time by using a hypotonic solution of NaCl. In contrast, using a hypertonic solution, intake is typically double the need. Using the same diuretic treatment, although the natriuresis occurs within ~1 h, the appetite appears only slowly over 24 h. Increased plasma levels of aldosterone parallel the increased intake; however, treatment with metyrapone blocks the rise in aldosterone but has no effect on appetite. Satiation of sodium appetite was studied in rats using sodium loss induced by chronic diuretic treatment and daily salt consumption sessions. When a simulated foraging cost was imposed on NaCl access in the form of a progressive ratio lever press task, rats showed satiation for NaCl (break point) after consuming an amount close to their estimated deficit. The chronic diuretic regimen produced hypovolemia and large increases in plasma aldosterone concentration and renin activity. These parameters were reversed to or toward non-depleted control values at the time of behavioral satiation in the progressive ratio protocol. Satiation mechanisms for sodium appetite thus do appear to exist. However, they do not operate quantitatively when concentrated salt is available at no effort, but instead allow overconsumption. There are reasons to believe that such a bias toward overconsumption may have been beneficial over evolutionary time, but such biasing for salt and other commodities is maladaptive in a resource-rich environment.

Characteristics of salt appetite in chronically sodium-depleted rats using a progressive ratio schedule of procurement

Satiation of sodium appetite of rats was studied using a protocol of sodium loss induced by chronic diuretic treatment and daily salt consumption sessions. In the first experiment in which NaCl was freely available from a drinking spout, rats consumed substantially more hypertonic NaCl than their estimated physiological deficit. In the second and third experiments, a simulated foraging cost was imposed on obtaining NaCl. In these experiments, rats were required to perform a progressive ratio lever press task to procure aliquots of hypertonic NaCl, and under these conditions they showed a break point or satiation for NaCl when they had consumed an amount close to their estimated deficit. In the fourth experiment, we found that the chronic diuretic regimen produced hypovolemia along with large increases in plasma aldosterone concentration and renin activity, and that all of these parameters were reversed toward non-depleted control values at the time of behavioral satiation in the progressive ratio protocol. Examination of natriuresis revealed that excessive intake of NaCl had no lasting benefit in this protocol: NaCl consumed in excess of need on 1 day was completely lost at the subsequent diuretic treatment. In the final two experiments, we showed that oral preloads of NaCl had no significant effect on progressive ratio procurement of NaCl, but that oral preloads reduced subsequent oral drinking. The data are discussed in terms of definitions of satiation of appetite in regard to the tightly regulated domain of body fluid homeostasis, and by extension, their relevance to systems such as energy homeostasis where set points appear to be less tightly regulated.

Alteration of renal adrenomedullin and its receptor system in the severely hypertensive rat: effect of diuretic

Objective We investigated the pathophysiological role of the renal adrenomedullin (AM) system, including the ligand, receptor, and amidating activity, in severe hypertensive rats. Method We studied three groups: control Wistar Kyoto rats (WKY), spontaneously hypertensive stroke-prone rats (SHR-SP), and diuretic-treated SHR-SP. We measured AM-mature, active form, and AM-total (active form+inactive form) in plasma and renal tissues, and mRNA levels of AM and AM receptor system components such as calcitonin receptor-like receptor (CRLR), receptor activity-modifying protein (RAMP) 2, and RAMP3 in renal tissues. Results SHR-SP had higher blood pressure, plasma neurohumoral factors, and lower renal function than WKY. SHR-SP had higher AM-mature and AM-total levels in plasma and renal tissues than WKY. Although the plasma AM-mature/AM-total ratio was similar in the two groups, AM-mature/AM-total ratio in renal tissues was higher in SHR-SP than in WKY. In addition, mRNA levels of AM in the renal cortex and medulla and the mRNA levels of CRLR, RAMP2, and RAMP3 in the renal cortex were higher in SHR-SP than in WKY. Chronic diuretic treatment decreased blood pressure and improved kidney function and neurohumoral factors, with reductions in plasma and renal AM system. Conclusion Upregulation of circulating and renal AM system may modulate pathophysiology in SHR-SP.

Upregulation of Na+ transporter abundances in response to chronic thiazide or loop diuretic treatment in rats.

Furosemide and hydrochlorothiazide (HCTZ) exert their diuretic actions by binding to apical Na(+) transporters, viz., the Na(+)-K(+)-2Cl(-) cotransporter in the thick ascending limb and the Na(+)-Cl(-) cotransporter in the distal convoluted tubule, respectively. We carried out semiquantitative immunoblotting and immunohistochemistry of rat kidneys to investigate whether chronic administration of furosemide or HCTZ is associated with compensatory changes in the abundance of Na(+) transporters downstream from the primary site of action. Osmotic minipumps were implanted into Sprague-Dawley rats to deliver furosemide (12 mg/day) or HCTZ (3.75 mg/day) for 7 days. To prevent volume depletion, all animals were offered tap water and a solution containing 0.8% NaCl and 0.1% KCl as drinking fluid. The diuretic/natriuretic response was quantified in response to both agents by using quantitative urine collections. Semiquantitative immunoblotting revealed that the abundances of thick ascending limb Na(+)-K(+)-2Cl(-) cotransporter and all three subunits of the epithelial Na(+) channel (ENaC) were increased by furosemide infusion. HCTZ infusion increased the abundances of thiazide-sensitive Na(+)-Cl(-) cotransporter and beta-ENaC in the cortex and beta- and gamma-ENaC in the outer medulla. Consistent with these results, beta-ENaC immunohistochemistry showed a remarkable increase in immunoreactivity in the principal cells of collecting ducts with either diuretic treatment. These increases in the abundance of Na(+) transporters in response to chronic diuretic treatment may account for the generation of diuretic tolerance associated with long-term diuretic use.

Initiating angiotensin converting enzyme inhibitors in mild to moderate heart failure in general practice: randomised, placebo controlled trial

Less than 50% of patients with heart failure in community practice receive an angiotensin converting enzyme inhibitor and then only usually at the instigation of or when prescribed by a...

Diuretic effects on cardiac hypertrophy in the stroke prone spontaneously hypertensive rat

The aim was to compare the effects of two diuretics, indapamide and hydrochlorothiazide, on cardiac hypertrophy in stroke prone spontaneously hypertensive rats (SHR-SP). Six week old SHR-SP, on a 1% sodium chloride water intake, were treated with oral indapamide (3 mg.kg-1 x d-1) or hydrochlorothiazide (20 mg.kg-1 x d-1) over a 44 d period. The hypertrophic process was evaluated by classical indices and by the morphological analysis of myocyte cross sectional area, coronary artery thickness, and immunohistochemical analysis of interstitial fibrosis. In the untreated SHR-SP on 1% sodium chloride, all animals developed severe hypertension and cardiac hypertrophy when compared to normotensive salt loaded WKY by 13 weeks of age. In salt loaded SHR-SP treated with indapamide or hydrochlorothiazide, systolic blood pressure was moderately decreased by the end of the treatment when compared with untreated SHR-SP, at 259(7) and 245(7) mm Hg respectively, v 300(11) mm Hg, p < or = 0.05. Myocyte enlargement appears to be the main feature involved in the development of cardiac hypertrophy in the SHR-SP. By the end of treatment both indapamide and hydrochlorothiazide prevented the development of cardiac hypertrophy evaluated by heart weight to body weight ratio [4.69(0.07) and 4.61(0.08) respectively, v 5.39(0.13), p < or = 0.001] and myocyte hypertrophy (-33% and -21% of the SHR-SP values, p < or = 0.001). Myocardial interstitial fibrosis and perivascular fibrosis were practically absent in the two treated groups. Our results allow the characterisation of SHR-SP cardiac hypertrophy and indicate that the two types of chronic diuretic treatment prevent SHR-SP cardiac hypertrophy with a drug specific efficiency.

The Physiologic Basis of Diuretic Synergism: Its Role in Treating Diuretic Resistance

Diuretic drugs usually improve edema when used judiciously. Some patients, however, become resistant to their effects. Diuretic resistance may result from dietary indiscretion, poor compliance, impaired bioavailability, imparied diuretic secretion into the lumen of the renal tubule, or because other drugs interfere with diuretic activity. When easily treatable causes of diuretic resistance have been excluded, resistance often reflects the intensity of the stimuli to sodium retention. Recent experimental work has indicated ways in which the kidney adapts to chronic diuretic treatment and has indicated how these adaptations may limit diuretic effectiveness. First, nephron segments downstream from the site of diuretic action increase sodium-chloride (NaCl) reabsorption because the delivered NaCl load increases. Second, diuretic-induced contraction of the extracellular fluid volume stimulates kidney tubules to retain NaCl until the next dose of diuretic is administered. Third, kidney tubules themselves may become hypertrophic because they are chronically stimulated by diuretic-induced increases in NaCl delivery. These adaptations all increase the rate of NaCl reabsorption and blunt the effectiveness of diuretic therapy. When diuretic resistance is present, using a second diuretic drug that acts in a different nephron segment is often effective. Recent experimental results suggest that a second class of drug may act synergistically with the first by blocking the adaptive processes that limit diuretic effectiveness. On the basis of an understanding of the mechanisms of diuretic adaptation and resistance, treatment regimens can be designed to block specific adaptive mechanisms and to improve diuretic therapy.

Occurrence of hypokalemia in suspected acute myocardial infarction and its relation to clinical history and clinical course

In 1350 patients with suspected acute myocardial infarction, serum potassium levels during the first 3 days in hospital was correlated to clinical history and clinical course. A higher incidence of hypokalemia was observed in women, in patients with hypertension, and in those on chronic diuretic treatment. Patients with anterior infarction had a higher incidence of hypokalemia than those with inferior infarction, as did patients with large as compared with small infarcts. No clear difference was observed between patients whose infarction was confirmed and those in whom the diagnosis was not confirmed. Independent predictors for hypokalemia were treatment with diuretics before admission to hospital, infarct size, and female sex. Hypokalemia during the first 3 days of hospitalization was associated with the occurrence of severe ventricular arrhythmias during hospitalization, but not with survival during a 5-year follow-up.

A simple and rapid method for the determination of the concentrations of magnesium, sodium, potassium and sodium, potassium pumps in human skeletal muscle

1. For the diagnosis of electrolyte disorders, data on skeletal muscle composition are often valuable, but rarely available. We have therefore developed a simple and rapid needle biopsy procedure for the determination of the concentrations of K+, Na+, Mg2+ and Na+, K+-pumps in muscle. 2. Using a Bergström needle, biopsies weighing around 25 mg were taken from the vastus lateralis muscle of 18 normal subjects (aged 44-86 years) and extracted with trichloroacetic acid (TCA). The concentrations of K+, Na+ and Mg2+ were 90.7 +/- 1.8, 31.9 +/- 1.6 and 9.5 +/- 0.2 mumol/g wet wt., respectively (means +/- SE). 3. The TCA extraction gave the same values as digestion with 65% HNO3 or 35% H2O2, could be used over the weight range 10-55 mg and showed a Mg2+ recovery of 101.7%. 4. The concentration of Na+, K+-pumps was quantified as the total capacity for [3H]ouabain binding. In vastus lateralis biopsies obtained from six normal subjects the mean value was 258 +/- 16 pmol/g wet wt. 5. Comparison of the concentrations of K+, Mg2+ and [3H]ouabain-binding sites in samples obtained post mortem showed modest variation among different muscles with varying fibre composition. 6. Measurements of the concentrations of K+, Na+, Mg2+ and Na+, K+-pumps in duplicate biopsies of the vastus lateralis yield values which seen representative for the total pool of skeletal muscle fibres and can be performed within a few hours.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of converting enzyme inhibition on the enhanced proximal sodium reabsorption induced by chronic diuretic treatment in patients with essential hypertension.

During chronic chlorthalidone treatment of patients with essential hypertension, distal tubular sodium reabsorption is continuously inhibited. At the same time, sodium balance is maintained by an increase of the proximal tubular sodium reabsorption. In the present study, we investigated whether this increase is caused by a stimulated renin-angiotensin system (RAS). For this purpose, the renal effects of converting enzyme inhibition (CEI) were evaluated in 12 patients with essential hypertension who remained hypertensive despite chronic chlorthalidone treatment. After 6 weeks of chlorthalidone, an intravenous injection of 10 mg enalaprilic acid decreased the mean arterial pressure (MAP) from 110 to 102 mm Hg. The effective renal plasma flow (ERPF) increased. However, glomerular filtration rate (GFR) and the fractional excretions of sodium, lithium and free water did not change significantly. After 2 additional weeks of chlorthalidone combined with enalapril 20 mg b.i.d., MAP fell to 90 mm Hg, ERPF remained elevated and plasma aldosterone concentration decreased. As in the acute study, no significant changes were detected in the GFR and the fractional excretions of sodium, lithium or free water. Extracellular fluid volume was not diminished during these 2 weeks. Fractional proximal sodium reabsorption during chronic chlorthalidone therapy was higher when calculated from free water clearance (91%) than from the lithium clearance (71%), but neither of the two were affected by acute or chronic CEI. The results of this study suggest that during chronic diuretic treatment, maintenance of sodium balance by increased proximal reabsorption is not dependent on the stimulated RAS, or alternatively, that this function of the RAS is exactly counterbalanced by another effect of CEI, possibly by the fall in blood pressure.

Changes in haemodynamics and body fluid volume due to enalapril in patients with essential hypertension on chronic diuretic therapy.

In 12 patients with essential hypertension who remained hypertensive despite chronic chlorthalidone treatment, the effect of 2 weeks of additional therapy with the converting enzyme inhibitor (CEI) enalapril on blood pressure and body fluid volumes has been evaluated. The objective was to examine the influence of a diuretic-stimulated renin-angiotensin-aldosterone system (RAAS) on haemodynamics and body fluid volume. Mean arterial pressure (MAP -21%), total peripheral resistance index (TPRI -22%) and plasma aldosterone concentration (PAC -39%) were decreased, and plasma renin activity (PRA 660%) was increased. The average heart rate (HR), cardiac index (CI), plasma volume (PV), blood volume (BV), extracellular fluid volume (ECFV) and body weight (BW) remained unchanged. A negative correlation was found between the per cent changes in ECFV and PAC. Thus, body fluid volumes during chronic diuretic treatment are well preserved even when the RAAS with its sodium retaining properties is suppressed by CEI. Possible mechanisms are a volume (not angiotensin II) - dependent stimulation of aldosterone and a fall in blood pressure.

Plasma renin in long-term diuretic treatment of hypertension: effect of discontinuation and restarting therapy.

1. Plasma renin activity, body weight and blood pressure were measured before and after 7 days' treatment with bendrofluazide in ten hypertensive subjects. They were then treated with bendrofluazide alone (5 mg daily) for a minimum of 3 years. The diuretic was then discontinued and the measurements were repeated before and again after 7 days with bendrofluazide. The results were compared with those obtained before chronic treatment with the diuretic. 2. Chronic diuretic treatment was associated with a persistent and progressive rise in plasma renin activity, that fell promptly to pretreatment levels when diuretics were discontinued. This was associated with significant weight gain but no immediate significant rise in blood pressure. 3. When acutely challenged with bendrofluazide the patients showed a greater increase in plasma renin activity on the second occasion than on the first. Three out of five patients with an initially subnormal diuretic treatment. 4. Chronic diuretic treatment increased the responsiveness of the juxtaglomerular apparatus in some hypertensive patients. 5. Classification of hypertensive patients into renin subgroups may be influenced by previous therapy, even when that therapy has been discontinued for 4 weeks. In particular 'low renin hypertension' may be masked by recent use of diuretics, as shown by three of the five patients in this subgroup in the present study.