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PubMed1983

Antihypertensive mechanism of diuretic treatment with chlorthalidone. Complementary roles of sympathetic axis and sodium.

Twenty-three patients with untreated mild to moderate essential hypertension had on the average an abnormally increased cardiovascular pressor responsiveness to exogenous norepinephrine (NE), while plasma and urinary NE, exchangeable body sodium and blood volume were normal. An increased pressor responsiveness to angiotensin II in these patients was associated with a tendency for low plasma renin activity (PRA). Compared to placebo conditions, treatment with chlorthalidone, 100 mg/day, for 6 weeks significantly decreased blood pressure and exchangeable sodium in these hypertensive patients but not in ten normal subjects; blood volume and heart rate were unchanged in both groups. Chlorthalidone induced a marked increase in PRA, but only a mild increase in angiotensin II pressor dose. In contrast, the diuretic caused a greater increase in NE pressor dose than in plasma NE in the hypertensive group, thus improving the disturbed relationship between plasma NE and NE responsiveness in these patients. No significant modification of plasma NE and NE responsiveness occurred in diuretic-treated normal subjects. In addition to sodium and the renin-angiotensin system, the sympathetic regulatory axis seems to be involved in the antihypertensive mechanism of chlorthalidone. Thiazide-like diuretics may decrease blood pressure in essential hypertension in part by lowering an abnormally high cardiovascular NE responsiveness without causing an equivalent increase in circulating NE.

Adult↗
PubMed1983

Thiazide diuretic effect on medullary collecting duct function in the rat.

The distal convoluted tubule is thought to be the principal site of action of thiazide diuretics, but, to our knowledge, there are no studies of their possible effects on collecting duct transport. Microcatheterization of the inner medullary collecting duct (IMCD) was carried out in rats undergoing a modest diuresis, natriuresis, and chloriuresis from hydro-chlorothiazide (2 mg/kg/hr) and in normal controls. Delivery of fluid, sodium, and chloride to the beginning of the IMCD was increased, but not significantly, while the load remaining at the papillary tip (end) of the duct was increased markedly by hydrochlorothiazide. Chloride reabsorption in the IMCD was affected most markedly; the chloride reabsorption between the beginning and end of the duct, as a fraction of the delivered load, was reduced from 70.4 +/- 5.4% in controls to insignificant amounts with hydrochlorothiazide (8.2 +/- 11.5%, P less than 0.001). The fraction of delivered sodium reabsorbed along the collecting duct was decreased from 78.5 +/- 4.9% in controls to 37.2 +/- 12.4% (P less than 0.005) in thiazide-treated rats and fluid reabsorption was decreased from 59.4 +/- 4.0% in controls to 31.9 +/- 5.1% (P less than 0.005). Small but significant potassium secretion into the IMCD occurred with hydrochlorothiazide, probably secondary to the marked increase in potassium delivery to the duct. Increased potassium excretion could account for a maximum of 50% of chloriuresis with hydrochlorothiazide. The observation that thiazide diuretics decrease chloride, sodium, and fluid reabsorption in the medullary collecting duct, like the recently demonstrated inhibitory effect of furosemide on this nephron segment, has significant implications for the rationale for diuretic use.

Animals↗
PubMed1989

Stimulation of renin secretion by non-diuretic sulfhydryl reagents.

Organomercurial diuretics stimulate renin secretion although the underlying cellular mechanisms remain undefined. Since organomercurials are also known to react with sulfhydryl groups, the present studies determined the effects of sulfhydryl reagents on renin secretion. The effects of the non-diuretic mercurial agent, parachloromercuriphenyl-sulfonate (PCMPS), as well as that of other sulfhydryl reagents, N-ethylmaleimide (NEM), N-phenylmaleimide (NPM) and monobromotrimethylammoniobimane (qBBR), on renin secretion were determined in rabbit renal cortical slices. All four reagents stimulated renin secretion. NEM, which has a high membrane permeability, stimulated secretion to a relatively small extent and its effects were not apparent for at least one hour. Conversely, PCMPS, which is much less permanent than NEM, produced the largest stimulation and these effects were apparent within one hour. The stimulation of secretion by sulfhydryl reagents was independent of the concentration of Ca2+, Na+, and K+ in the incubation media, suggesting that the stimulation is not secondary to alterations of intracellular ion concentrations. These results raise the possibility of direct involvement of sulfhydryl groups of particular membrane protein(s) of the juxtaglomerular (JG) cells in some steps leading to renin secretion, and raise the possibility that sulfhydryl reactivity might in part account for the stimulatory effects of organomercurial and other diuretics.

Animals↗
PubMed1978

Calcitonin diuretic effect in the rabbit.

In an attempt to study the renal effects of Calcitonin (porcine CT) in the rabbit, the excreted fractions of filtered water, osmolality, sodium, potassium and chloride, and the calcium and phosphorus urinary excretions were studied during isotonic (ISD) and hypertonic (HSD) saline diuresis. Four doses (0.1, 0.8, 4 and 20 IU MRC/kg were perfused during one hour in I.S.D.; 4 and 20 IU MRC/kg in HSD. During ISD, Calcitonin at doses of 4 and 20 IU MRC/kg/hr significantly increased the diuresis and the Na+, Cl-, K+, PO4 3-, Ca2+ excreted fractions. This effect was also observed, to a lesser extent, at a dose of 0.8 IU MRC/kg/hr, whereas 0.1 IU MRC/kg/hr produced no significant effect. During ISD, a log dose related effect of CT appeared to exist with all studied parameters. Moreover, a biphasic pattern of free-water clearance was observed during ISD: this parameter increased during the first half hour of CT perfusion, and then decreased dramatically. During HSD, CT perfusion induced a decrease of free-water reabsorption and urinary osmolality/plasma osmolality ratio. These results suggest that the diuretic effect and saliuretic effect of CT (in the rabbit) are mainly the consequence of the decrease of the proximal reabsorption of sodium. The possibility of a second site of action is discussed. The diuretic effects of CT are compared to data observed with the well-known diuretic drugs.

Animals↗
PubMedDate not supplied

[Age-dependency of isotope drainage in diuretic renograms].

OBJECTIVE: The aim of the study was to establish normal values of the isotope drainage in diuretic scintigrams for children of different age-groups. Isotope drainage was determined 30 minutes after the application of technetium- (99m)MAG 3 as well as 15 minutes after the following application of furosemide. METHODS: We analysed the data from 274 investigations in sonographically normal renal units (RU) contralateral to kidneys with ureteropelvic junction obstruction or non-refluxing primary megaureters. RESULTS: There was a significant age-dependency of isotope drainage during the first weeks of life. In 79 RU the results of the first diuretic renogramm were compared with the follow-up examinations. The reliability of the measurements was lowest in children initially investigated during the first six weeks of life. If both the investigations were performed thereafter, no significant difference was found between the results. CONCLUSIONS: The isotope drainage of the sonographically normal contralateral RU seems to be a sufficient marker for the meaningfulness of the diuretic renogram. In urinary tract dilatation, mistakes regarding the interpretation of isotope drainage may be minimized by taking the measurements in the normal contralateral RU in account and by comparing them with age-referred normal values.

Child↗
PubMed1987

Acute changes in plasma renin activity, plasma aldosterone concentration and plasma electrolyte concentrations following furosemide administration in patients with congestive heart failure--interrelationships and diuretic response.

We studied the effects of furosemide on plasma renin and plasma aldosterone in 8 patients with mild to moderate congestive heart failure. In particular, we tried to correlate these effects with changes in plasma electrolyte concentrations and with the diuretic response on furosemide. We concluded that the diuretic response in patients with congestive heart failure is not dependent on the initial serum renin nor on the initial serum aldosterone concentration. The diuretic response did not correlate either with the changes in serum renin and/or serum aldosterone concentration. Serum renin and serum aldosterone correlated mutually before and after intravenous furosemide. We confirmed the inverse correlation between serum sodium and serum renin. SeNa and SeK correlated at all times with serum aldosterone; SeCl correlated with serum aldosterone only before intravenous furosemide administration. Indirect evidence could be provided that in patients with congestive heart failure a decreased renal blood flow is present, using the urinary beta 2-microglobulin concentration. Aldosterone has again, indirectly, proved to be integrated in the renal magnesium handling.

Aged↗
PubMed1983

[Case report on the administration of diuretics during pregnancy].

Diuretics potentiate existing hypovolaemia and hämoconcentration in patients suffering from toxemia of pregnancy. This effect also applies to the fetus. A case is presented of an intrauterine spontaneous thrombosis in the inferior vena cava and its tributaries in a fetus with resulting perinatal death during long-term diuretic therapy because of edema in the mother in the third trimester. Basing on this example, the present state of assessment and necessity of treatment of the symptom "edema" in late pregnancy is discussed, with the conclusion that administration of diuretics, if it becomes necessary in a life-threatening state of the pregnant mother (pulmonary edema or oliguria in pre-eclampsia or eclampsia) is indicated only with monitoring of the hematocrit and central venous pressure.

Adult↗
PubMed2005

Position of fixed-dose combinations containing an AT(1)-receptor blocker and a thiazide diuretic.

Treatment of hypertension remains a difficult task despite the availability of different types of medications lowering blood pressure by different mechanisms. In order to reach the target blood pressures recommended today combination therapy is required in most patients. The co-administration of two drugs with different impacts on the cardiovascular system markedly increases the antihypertensive effectiveness without altering adversely tolerability. Fixed low-dose combinations are becoming a valuable option not only as second-line, but also as first-line therapy. In this respect the co-administration of thiazide diuretic with an AT(1)-receptor blocker is particularly appealing. The diuretic-induced decrease in total body sodium activates the renin-angiotensin system, thus rendering blood pressure maintenance angiotensin II-dependent. During blockade of the renin-angiotensin system low doses of thiazides generally suffice, allowing the prevention of undesirable metabolic effects. Also, blockade of the AT(1)-receptor, particularly when angiotensin II production is enhanced in response to diuretic therapy, is expected to be beneficial, since angiotensin II seems to contribute importantly to the pathogenesis of cardiovascular and renal complications of hypertension.

Angiotensin II Type 1 Receptor Blockers↗
PubMed1994

Hostility and the response to diuretic in mild-to-moderate hypertension.

Forty-two patients with mild-to-moderate hypertension between the ages of 35 and 65 (23 men, 19 women) were studied to determine whether psychological characteristics can help differentiate between responders and nonresponders to diuretic (hydrochlorothiazide 25 mg and triamterene 50 mg). To qualify for inclusion in the study, the subjects were required to have a mean unmedicated clinic diastolic blood pressure (DBP) between 95 and 110 mm Hg. Positive response to diuretic was defined as a reduction in clinic DBP < or = 90 mm Hg. Of the 42 subjects, 22 were responders to diuretic, achieving a BP level of 129/86 mm Hg, a reduction of 16/11 mm Hg from their unmedicated level. Nonresponders achieved a reduction of 8/4 mm Hg. Compared with nonresponders, responders were characterized by slightly lower initial BP levels and significantly lower scores on the Buss-Durkee Hostility Inventory and several subscales of this test. The pattern of results indicated higher levels of suppressed hostility in the nonresponders. Ambulatory BP data paralleled the clinic BP changes.

Adult↗
PubMed1991

Indapamide: a diuretic of choice for the treatment of hypertension?

In recent years, the therapeutic approach to mild hypertension has evolved from a stepped care approach to one including varied, initial monotherapies, with the selection of drug based on factors present in an individual patient, followed by combination therapy. The greatest cumulative experience of the value of antihypertensive therapy has been obtained with diuretics. The reduction in risk of cardiovascular disease with successful antihypertensive therapy using conventional agents, including diuretics, is not as great as might have been anticipated by the magnitude of change in blood pressure. This could be due to antecedent cardiovascular injury prior to therapy or to risk factors induced by therapy. The recent introduction of a new generation of drugs with combined diuretic and hypotensive effects that reduce blood pressure without inducing the biochemical changes associated with thiazides, offers an opportunity to evaluate this question. Indapamide is the first of this new generation to be released. Its pharmacologic characteristics show that it has the prerequisites to be considered a first-line drug for use in hypertension. It meets the requirements of a Phase II or second generation drug in that it has similar efficacy, but less short term toxicity than first generation drugs. It has been introduced at a cost that is competitive with thiazides and potassium-sparing combination drugs and is cheaper than many other classes of antihypertensive drugs. The major caution in promoting its use is that its long term effect on morbidity and mortality in hypertensive disease has not yet been evaluated. In summary, this is a promising new drug that has the potential to replace first generation thiazides in the routine management of hypertension.

Blood Glucose↗
PubMed1989

Rapid, contrast-enhanced, diuretic magnetic resonance imaging of unilateral partial ureteral obstruction. An experimental study in micropigs.

The value of rapid, contrast-enhanced, diuretic magnetic resonance (MR) imaging (using ferrioxamine B and furosemide) in demonstrating partial unilateral ureteral obstruction and the potential of such MR imaging in differentiating obstructive from nonobstructive hydronephrosis was assessed in six micropigs. MR imaging (0.35 Tesla, partial-flip technique with repetition time [TR] of 125 milliseconds, echo-delay time [TE] of 20 milliseconds, and flip angle of 70 degrees) was performed before, and at 5, 12, and 19 days after partial ureteral obstruction. Additionally, MR images were acquired 5, 12, and 19 days after release of obstruction. The diuretic was injected 10 minutes after the contrast medium. MR findings were correlated with results from nuclear scintigraphy (99mTc-DMSA uptake). MR images provided good morphologic detail from which renal size, parenchymal thickness, and degree of hydronephrosis could be determined. Contrast medium allowed assessment of cortical uptake and urinary excretion. The course of cortical signal enhancement best characterized the difference between obstructive and nonobstructive hydronephrosis. Normal kidneys and kidneys with nonobstructive hydronephrosis showed progressive decrease in cortical signal enhancement (-11.7% within 40 minutes) after furosemide injection. The kidneys with obstructive hydronephrosis demonstrated a plateau of signal enhancement without decrease (-0.7% within 40 minutes). These results demonstrate the utility of rapid contrast-enhancing, diuretic MR imaging in differentiating obstructive from nonobstructive hydronephrosis.

Animals↗
PubMed2005

Renal pelvis volume during diuresis in children with hydronephrosis: implications for diagnosing obstruction with diuretic renography.

PURPOSE: We measured the volume of the renal pelvis during diuretic renography (DR) in children with normal and hydronephrotic kidneys to determine if changes in pelvic volume could affect the accuracy of DR in diagnosing obstruction. MATERIALS AND METHODS: We studied 18 patients 1 month to 10 years old with unilateral hydronephrosis ultimately proved to be either obstructive or nonobstructive. Simultaneous DR and ultrasound were performed with patients supine using the gamma camera. Ultrasound measurements of the renal pelvis in 3 dimensions, obtained before and at intervals after diuretic injection, were used to calculate renal pelvic volume. The contralateral normal kidneys were used as controls. RESULTS: Between 15 and 60 minutes after diuretic injection the renal pelvis enlarged to a maximum volume in all hydronephrotic and normal kidneys and then gradually decreased in size. Mean average increase in volume for hydronephrotic kidneys ranged from 46% in obstructed kidneys to 88% in nonobstructed kidneys. Volume expansion caused dilution of isotope within the renal pelvis, which resulted in prolongation of elimination half-time (T1/2) in 42% of nonobstructed hydronephrotic kidneys sufficient to register an obstructed washout pattern. However, there were no differences in the initial pelvic volume or the rate or extent of increases or decreases in pelvic volume that would permit nonobstructed hydronephrotic kidneys to be distinguished from obstructed ones. CONCLUSIONS: The renal pelvis enlarges during diuresis in children with hydronephrosis. This enlargement causes dilution of isotope within the renal pelvis during DR, which prolonged the isotope washout rate or T1/2 sufficiently to produce an obstructed washout pattern in more than 40% of hydronephrotic kidneys that were ultimately proved to be nonobstructed. This misdiagnosis of obstruction is particularly likely to occur in children younger than 2 years because pelvic volume expansion is so exaggerated. Consequently, T1/2 appears to be particularly vulnerable to inaccuracy in diagnosing obstruction in this age group, and, therefore, it should not be relied on as an operative determinant.

Child↗
PubMed1992

Intracellular free magnesium in lymphocytes from patients with congestive cardiac failure treated with loop diuretics with and without amiloride.

Cellular Mg2+ depletion has been reported in patients on long term diuretic therapy. We therefore measured lymphocyte free Mg2+ concentrations in patients with congestive cardiac failure treated with loop diuretics or a frusemide/amiloride mixture (Frumil) and compared them with control subjects. There was no correlation between lymphocyte free Mg2+ levels and plasma Mg2+ concentrations. Patients treated with loop diuretics did not show lymphocyte intracellular free Mg2+ depletion compared with normal controls, and those on Frumil showed higher intracellular free Mg2+ levels than normal.

Amiloride↗
PubMed2006

Thiazide diuretic prescription and electrolyte abnormalities in primary care.

AIMS: Thiazide diuretics have a number of well-documented metabolic adverse effects. The aim of this study was to estimate the frequency of hyponatraemia and hypokalaemia amongst patients taking a thiazide diuretic in primary care. METHODS: A computerized search of the electronic prescribing and laboratory records of six UK general practices was performed. Of the 32 218 adult patients identified, 3773 had received at least one prescription for a thiazide between the years 1990 and 2002. RESULTS: Detailed prescribing data were available for 2942 patients of whom 951 (32.3%) had a recorded check of their electrolytes. One hundred and ninety-six (20.6%) had a sodium and/or potassium concentration below the normal range. The sodium distribution had a negative skew (-1.8) and in 130 (13.7%) patients was within the hyponatraemic range. Hypokalaemia was less common, occurring in 79 (8.5%) patients. Hyponatraemia was significantly associated with increased age; the odds ratio for developing hyponatraemia in patients over 70 years was 3.87 compared with those of < or = 70 years. Hypokalaemia was significantly associated with increased thiazide dose. CONCLUSIONS: Prescription of a thiazide diuretic in primary care is associated with a high frequency of hyponatraemia and hypokalaemia. Thiazides should be prescribed at low dose and the risk of hyponatraemia, especially in the elderly, should be considered and monitored for when prescribing these agents.

Adult↗
PubMed1982

Diuretic radionuclide renography in upper urinary tract obstruction.

Diuretic renography using radioidine sodium hippurate and a frusemide stimulus was used to differentiate between obstructive and nonobstructive dilatation of the urinary tract. Information was recorded by a gamma camera on line to a computer. Sixty-seven uretero-renal units (URU) were studied in 33 patients with an average age of 91/2 years. The diuretic renogram correctly indicated obstructions in 18 URU but gave false positive results in another five. Of these five, four had severely impaired function. The renogram indicated nonobstruction in 49 URU, and gave false negative results in another two; of these two one patient had a duplex kidney with a poorly functioning ureteric segment and the other patient had gross reflux and megaureters. The diuretic renogram is useful in the investigation of equivocal upper urinary tract obstruction but may be unreliable in situations of inadequate renal function.

Adolescent↗
PubMed1995

Intrarenal dopamine participation in frusemide diuretic and natriuretic responses to frusemide.

1. Dopamine (DA) involvement in the renal response to frusemide was analysed using the isolated perfused rat kidney preparation. Endogenous DA levels were increased through the infusion of its precursor levodopa (LD) (0.5 or 1 microM) whereas benserazide (50 or 100 microM), an inhibitor of the enzyme L-dopa-decarboxylase, was used to decrease DA synthesis. 2. Frusemide administration (0.3-20 nmols) induced a dose-dependent increase in fractional excretion of water (FE H2O), sodium (FE Na+) and glucose (FEG). FE Na+ elicited by the diuretic was enhanced 30-40% by 0.5 microM of LD (n = 5, P < 0.05), and 60-80% by LD 1 microM (n = 5, P < 0.05). FE H2O produced by the diuretic was enlarged 80-100% by 0.5 microM (n = 5, P = 0.05), and 130-170% by 1 microM of LD (n = 5, P < 0.01). The increase produced by both concentrations of LD on FEG was 200% for the lowest dose of the diuretic (n = 5, P < 0.01), and 90% for the highest (n = 5, P < 0.05). 3. Benserazide (BZ) (100 microM) decreased the F.E. Na+ induced by frusemide (n = 5, P < 0.05) by 32-42%, and completely abolished frusemide effects on FE H2O and FEG (n = 5). 4. In conclusion, our results suggest that endogenous dopamine participates in the frusemide-induced diuresis and sodium excretion within the kidney, and that the participation of extrarenal factors is not essential for this effect. Dopamine may be involved in frusemide-induced inhibition of proximal sodium reabsorption.

Animals↗
PubMed1968

Diuretic responses to water-load in four strains of mice.

1. The kinetics of excretion of water, sodium and potassium following a stomach load of water, with and without an initial injection of vasopressin, are described in each of four strains of mice: RAP, CBA/FaCam, Peru and A/Cam.2. In general there was a diuretic lag followed by an increase in the rate of excretion of water to a maximum, after which the rate of excretion fell again to near resting levels. The rate of excretion of sodium rose to an initial maximum which significantly preceded the maximum rate of water excretion. The rate of excretion of sodium then fell to a minimum at a time not significantly different from the time of maximum rate of water excretion.3. The effect of an initial injection of vasopressin was to increase and to prolong the initial rise in rate of sodium excretion. The maximum rate of water excretion and the minimum sodium concentration were delayed, but the levels eventually reached were not significantly altered, by the vasopressin injection.4. The strains of mice differed significantly in diuretic lag, maximum rate of diuresis, and 3 hr excretion of water and electrolytes.5. The strains also differed significantly in the effects of vasopressin, both in increasing diuretic lag and in increasing sodium excretion. There was no correlation between the antidiuretic and natriuretic effects of vasopressin.

Animals↗
PubMed1980

Diuretic treatment of resistant hypertension.

In patients with hypertension resistant to three or four drugs including a thiazide diuretic substitution of frusemide for the thiazide, or the addition of spironolactone, produced significant reductions in blood pressure and body weight. The response did not depend on the presence of overt fluid retention, renal impairment, or the use of antihypertensive drugs of high potency. Women had larger responses than men. Expansion of the plasma or extracellular fluid volume is an important cause of resistance to treatment even when a thiazide diuretic is used. An increase in diuretic treatment should be tried before using the postganglionic adrenergic blockers or minoxidil in resistant hypertension.

Adult↗