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PubMed1979

Obstructive uropathy and nephrogenic diabetes insipidus in infants.

The syndrome of acute post-obstructive nephrogenic diabetes insipidus is a rare phenomenon. The lesion is acquired during the pre-diuretic phase, owing to antidiuretic hormone resistance of the distal tubule as well as a severe concentrating defect. The diuretic phase after relief of obstruction can result in a massive, sustained and life-threatening diuresis. Sodium restriction and thiazide diuretics produce a mild volume contracted state, enhancing sodium and water reabsorption, primarily in the proximal tubule and possibly in the distal tubule owing to aldosterone. The recognition and differentiation of this unique pyloric syndrome from other more common post-obstructive diuretic states are important for all urologists who are responsible for the care of children.

Chlorothiazide↗

PubMedDate not supplied

Comparison of the diuretic effect of furosemide mixed with human albumin or fresh frozen plasma for patients with hypoalbuminemia in the intensive care unit.

BACKGROUND: Diuretics are commonly used in the intensive care unit (ICU) for patients with fluid over-loading. Hypoalbuminemia is a major cause of diuretic resistance. Albumin mixed with furosemide can promote diuresis and sodium excretion in patients with hypoalbuminemia. The purpose of this study is to compare the diuretic effect of furosemide (FU) mixed with human albumin (HA) or fresh frozen plasma (FFP) in ICU patients with hy-poalbuminemia. METHODS: Patients with fluid overloading and hypoalbuminemia who needed diuretic treatment were enrolled and were divided into 2 groups: the first group having clearance of creatinine (CCr) >20 ml/min, and the second group having CCr < or = 20 ml/min. FU (60 mg) mixed with HA (HA group), 60 mg FU mixed with FFP (FFP group) and water (placebo group) were given intravenously to these patients for 60 minutes in random order on the first, third and fifth day. After drug administration, 8-hour urine was collected, and urine amount and urinary sodium excretion were checked. RESULTS: Both the HA group and the FFP group had significantly higher urinary volume and sodium excretion than the placebo group in the patients with CCr >20 ml/min or CCr < or = 20 ml/min (p < 0.01). In the patients with CCr >20 ml/min, there was no difference in the amount of urine excretion and cumulative urinary sodium excretion between the HA group and FFP group. In the patients with CCr < or =ml;20 ml/min, the HA group had a significantly higher urine output and urinary sodium excretion than the FFP group (p < 0.05). CONCLUSIONS: In ICU patients, 60 mg FU mixed with HA or FFP has a similar diuretic effect in patients with CCr >20 ml/min. FFP is an effective alternative choice for improving diuresis for ICU patients with hypoalbuminemia. In patients with CCr < or = 20 ml/min, albumin mixed with 60 mg FU has a superior diuretic effect compared with FFP mixed with FU.

Adult↗

PubMed1983

How diuretics lower blood pressure.

Thiazides produce an average loss of 2 L of extracellular fluid volume, of which about 300 ml is plasma volume, during the first 48 hours of administration, and this reduction is maintained without further loss for as long as the drug is given. Do thiazides lower blood pressure by volume depletion or by direct vasodilator action? As evidence against the vasodilator theory, these facts may be adduced: (1) thiazides do not lower blood pressure in patients (with renal disease) who cannot obtain a diuresis, and (2) other diuretics and diets very low in sodium also reduce blood pressure and volume to a similar degree. A related hypothesis is that thiazides reduce total peripheral vascular resistance (TPR) by "dehydrating" vascular walls. However, direct measurements in small arteries failed to confirm such changes. There is, however, a fall in TPR after long-term treatment, although initially cardiac output falls and TPR remains unchanged. How these long-term readjustments occur remains unknown, although several hypotheses have been advanced.

Benzothiadiazines↗

PubMed2006

Hyponatremia associated with selective serotonin-reuptake inhibitors in older adults.

OBJECTIVE: To review the incidence, risk factors, mechanism, times of onset and resolution, and treatment of hyponatremia associated with selective serotonin-reuptake inhibitors (SSRIs). DATA SOURCES: An English-language literature search was conducted using MEDLINE (1966-December 2005) using the search terms selective serotonin-reuptake inhibitor, hyponatremia, syndrome of inappropriate secretion of antidiuretic hormone, citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline. Additional references were identified by reviewing bibliographies of articles retrieved. STUDY SELECTION AND DATA EXTRACTION: Relevant data were extracted from published reports, letters, and studies of humans with hyponatremia and/or syndrome of inappropriate secretion of antidiuretic hormone (SIADH) secondary to SSRIs. All articles identified from data sources were reviewed for relevant information. Applicable information was included in this review. DATA SYNTHESIS: Numerous case reports, observational studies, and case-controlled studies, as well as one prospective clinical trial, have reported hyponatremia associated with SSRI use, with the incidence varying from 0.5% to 32%. Risk factors for the development of hyponatremia with SSRIs include older age, female gender, concomitant use of diuretics, low body weight, and lower baseline serum sodium concentration. In published reports, hyponatremia developed within the first few weeks of treatment and resolved within 2 weeks after therapy was discontinued. The mechanism by which SSRIs cause hyponatremia is thought to be secondary to development of SIADH. Treatment of isovolemia hypotonic hyponatremia associated with SSRI use includes water restriction and mild diuresis with a loop diuretic. More severe cases may be treated with higher doses of loop diuretics and hypertonic saline. There have been few reports of rechallenge with the same or another SSRI or substitution of another agent from a different therapeutic class. In some, but not all, cases hyponatremia recurred. CONCLUSIONS: Practitioners should be on the alert for this potentially life-threatening adverse event, especially in older adults with other risk factors for developing hyponatremia.

Aged↗

PubMed2000

Torasemide is an effective diuretic in the newborn rabbit.

The effect of intravenous (i.v.) torasemide on diuresis and renal function was evaluated in three groups of normoxemic, 5- to 10-day-old, newborn New Zealand White rabbits. The animals of group 1 received 0.2 mg/kg of torasemide i.v., whereas in group 2 an i.v. dose of 1.0 mg/kg was given. The third group of animals received a bolus i.v. dose of 1.0 mg/kg torasemide with continuous i.v. replacement of estimated urinary fluid and electrolyte losses. Torasemide proved to be an effective, potassium-sparing diuretic, without significant effect on glomerular filtration rate (GFR). Renal blood flow (RBF) fell and the renal vascular resistance (RVR) rose in all three groups of animals, although the rise in RVR in group 3 was not significant. These changes in renal hemodynamics were most pronounced in the animals of group 2 and are probably secondary to torasemide-induced hypovolemia (2.8% loss of body weight) and accompanying humoral reactions, such as an increase in angiotensin II (not measured). When the latter is prevented by simultaneous re-infusion of an electrolyte solution (group 3), replacing urinary losses, GFR increases and the changes in RBF and RVR are blunted. We conclude that torasemide is an effective, potassium-sparing diuretic in newborn rabbits. No evidence was found for a vasodilatory action of the drug.

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↗

PubMed1990

[Combination of a carbon dioxide bath and a diuretic--follow-up study of several days].

A series of 22 men underwent a 30 minute carbon dioxide bath and was simultaneously administered Hydrochlorothiazide SPOFA. Their renal response was studied, and that both separately to the bath or the diuretic and to their combination. Diuresis was increased by 200 l x 10(-3) after the carbon dioxide bath and by 500 l x 10(-3) after hydrochlorothiazide. This increase was even further enhanced after the combination of the two treatments. Sodium excretion showed a similar increase, whereas kaliuresis did not exhibit such a marked rise and the differences between the response to the bath and to the diuretic were small. Repeated combination of the carbon dioxide bath and the diuretic resulted in a slightly increasing diuresis over the days studied. The authors emphasize the necessity to understand the bath--drug interactions particularly in balneological practice and substantiate the advantage and usefulness of the combination studied in indicated cases.

Adult↗

PubMed1983

Renal function in patients with cystic fibrosis.

Renal handling of sodium, potassium, calcium and phosphorus was investigated in 9 patients with cystic fibrosis (CF). Both under baseline conditions and during saline-induced diuresis, urinary excretion rate of sodium (UNaV), potassium, phosphorus and calcium did not differ significantly from control values although the fractional excretion of sodium was significantly higher in patients with CF during saline diuresis. When distally acting diuretics were administered, this difference between CF patients and controls was magnified and in addition, UNaV in CF patients was also significantly higher than in controls. Following saline loading the increment in glomerular filtration rate (GFR) in patients with CF was significantly lower than that of controls. We conclude that patients with CF when subjected to volume expansion demonstrate a lower tubular reabsorptive capacity of sodium as well as a reduced ability to increase their GFR. The defect in sodium reabsorption is probably located in the proximal tubule.

Calcium↗

PubMed1980

Diuretic effect of intraventricular and intravenous infusions of noradrenaline in conscious sheep.

Infusion of noradrenaline at rates between 32-160 nmol.min-1 for 30 min into one lateral cerebral ventricle of conscious sheep caused a diuresis which was accompanied by negative solute-free water reabsorption and which lasted for 90-120 min. The range of noradrenaline infusion rates used reflects differences between individual animals in the rate of infusion necessry to cause diuresis. Intracerebroventricular (ICV) infusion of noradrenaline at half the diuretic rate caused no significant changes in urine flow. The diuresis induced by ICV noradrenaline infusion was prevented by concurrent ICV administration of the alpha-adrenergic antagonist, phentolamine, but was not prevented by concurrent ICV administration of the beta antagonist, propranolol, or by concurrent intravenous infusion of phentolamine. Intravenous infusion of noradrenaline at rates that were diuretic by ICV infusion caused a diuresis of approximately 30 min duration which coincided with the period of intravenous noradrenaline infusion. This diuresis was prevented by concurrent intravenous infusion of phentolamine. These results were interpreted as indicating that the higher rates of ICV infusion of noradrenaline caused the prolonged water diuresis by acting at a site in the brain and, thereby, inhibiting the release of endogenous vasopressin. ICV infusion of noradrenaline at all rates was followed by a reduction in mean arterial blood pressure and pulse pressure with variable changes in heart rate and by depression of the rates of renal clearance of PAH, potassium and total solute.

Animals↗

PubMed1975

Electrolyte excretion and free-water production during onset of acute diuresis.

The concentration of major urinary solutes was studied in ureteral urine collected at 15- to 30-s intervals at the onset of acute diuresis induced in anesthetized dogs either by high-ceiling diuretics (mainly ethacrynic acid) or by osmotic diuretics. Phosphate/inulin clearance ratios remained unchanged; potassium/inulin clearance ratios rose rapidly. Principal attention is given to the mechanisms underlying a transient rise in urinary sodium and chloride concentrations during the onset of diuresis. When the data are corrected for washout artifacts from the pelvis and ureter, it can be shown that the initial collection periods are associated with a transient increase in free-water production and by the simultaneous secretion of urea from the interstitium into the tubular fluid. The former coincides in time with the rise in urinary chloride concentration and represents an augmentation of water reabsorbed in the collecting duct, which is relatively impermeable to chloride. Both responses are quantitatively consistent with the transition from a hyperosmotic to isosmotic medullary interstitium.

Animals↗

PubMed1995

[Effects of potassium chloride and triamterene on kaliuresis, natriuresis and diuresis in congestive heart failure].

KCl and triamterene were given to 52 patients (27 males and 25 females with CHF) aged 21-82 years. Large-dose KCl (6 g daily) apparently stimulate kaliuresis, natriuresis and diuresis. As a rule, this is associated with a rise or a fall of plasma potassium concentrations. In the latter case potassium elimination runs more actively and may involve both introduced and body's potassium. As low and moderate doses of KCl (1-4 g daily) showed neither natriuretic nor diuretic effects while enhanced kaliuresis occurred in half of the patients only, did not lower potassium concentrations in plasma they are preferable. Daily treatment with triamterene is characterized by inhibition of its K-retaining action on administration day 2-3. Within first 2 days of triamterene discontinuation all the retained K eliminates from the body. Diuretics-induced metabolic alkalosis decreased intensification of natriuresis and diuresis resultant from large-dose KCl treatment.

Adult↗

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↗

PubMed1999

The influence of frusemide formulation on diuretic effect and efficiency.

AIMS: Changes in drug delivery rate may result in clinically important changes in drug effects. For the loop diuretic frusemide, it would be desirable to develop controlled release preparations, that could maintain an effective urinary excretion rate over a prolonged period of time. The aim of this study was to investigate the influence of frusemide formulation on frusemide recovery, diuretic effect and efficiency. METHODS: Twelve subjects were given 60 mg of four different frusemide controlled release formulations in a single-dose, double-blind, randomized 4-way cross-over design. The formulations were three study drugs with different extended dissolution rates (ER1Tab, ER2Tab and ER3Caps ) and one reference drug (LR). Urinary volume and contents of frusemide in urine were measured in samples collected over 24 h. RESULTS: Substantial differences in frusemide recovery and diuretic efficiency were observed between LR and all other formulations. At 24 h, mean total frusemide recoveries of ER1Tab, ER2Tab and ER3Caps were 52%, 36% and 57% lower, respectively, compared with LR (P<0.01). Also at 24 h, mean total diuretic efficiency for ER1Tab, ER2Tab and ER3Caps was 83%, 31% and 135% higher, respectively, compared to LR. The rapid dissolution and absorption of LR resulted in a high diuretic response from 0 to 3 h after dosing. However, from 0 to 24 h, there were no differences in diuretic response between the formulations. CONCLUSIONS: Controlled release formulations of frusemide with a low and extended rate of dissolution lead to a more prolonged absorption and subsequent diuresis, but still maintain a similar cumulative response, due to their higher diuretic efficiency.

Adolescent↗

PubMed2004

Comparison of three different diuretic renal scintigraphy protocols in patients with dilated upper urinary tracts.

PURPOSE: To compare 3 different diuretic renal scintigraphy protocols in patients with dilated upper urinary tract. MATERIALS AND METHODS: Three diuresis renography protocols were performed in 22 adult patients (28 kidneys) with upper urinary tract dilatation. The diuretic was given 20 minutes after (F+20), at the same time as (F+0), and 15 minutes before (F-15) radionuclide administration. The mean age was 29.8 years (range, 18-43 years). The 3 protocols were identical, except for the time of injection of furosemide. The F+0 protocol could not be performed in 1 and F-15 in 2 of the patients. Each of the 3 protocols was performed for the rest of the patients. The results were classified as nonobstructive, equivocal, and obstructive according to the renogram images and curves. RESULTS: None of the patients showed equivocal results in both F+0 and F-15 protocols. In the F+20 studies, 7 of the 28 kidneys were evaluated as equivocal. Of these, 5 kidneys showed nonobstructive and 2 kidneys revealed obstructive renogram patterns with the other 2 protocols (F+0 and F-15). Moreover, one kidney, which was evaluated as nonobstructive in the F+20 protocol, showed an obstructive pattern in both F+0 and F-15 protocols. All of the kidneys showing obstructive patterns in the F+20 study also revealed obstruction in the F+0 and F-15 investigations. We could not find any difference between the renogram patterns of F+0 and F-15 investigations. CONCLUSIONS: F+0 and F-15 protocols allow clarification in cases of equivocal F+20 studies. Because the F+0 study is more practical and shorter, we suggest the F+0 method when equivocal results are obtained by an F+20 study or as a single test when there is only one opportunity to confirm or exclude the presence of obstruction.

Adolescent↗

PubMed2003

Postoperative intra-abdominal pressure and renal function after liver transplantation.

HYPOTHESIS: Intra-abdominal hypertension frequently threatens renal function early after orthotopic liver transplantation (OLT). DESIGN: A prospective study of consecutive patients who underwent OLT. SETTING: The intensive care unit of a National Health Service teaching hospital. PATIENTS AND MAIN OUTCOME MEASURES: The intra-abdominal pressure (IAP) of 108 consecutive patients who underwent OLT was postoperatively measured 3 times a day for 72 hours using the urinary bladder technique. Intra-abdominal hypertension was defined as an IAP of 25 mm Hg or higher. RESULTS: Thirty-four patients (31%) had a high IAP. Acute renal failure developed in 17 recipients (16%), 11 (65%) of whom had intra-abdominal hypertension (P<.01), with a mean +/- SD IAP of 27.9 +/- 9.9 mm Hg vs 18.6 +/- 5.2 mm Hg in those without acute renal failure (P<.001). The subjects with a high IAP were more frequently administered loop diuretics to maintain adequate diuresis (P<.001) and had a low mean arterial pressure on the day of surgery (P<.01), despite the fact that they were given more intravenous fluids (P<.01) and did not differ in the need for inotropic drugs. Logistic regression analysis showed that intraoperative transfusions of more than 15 U, respiratory failure, and intra-abdominal hypertension (P<.01) were independent risk factors for renal failure. The length of intensive care unit stay was similar in the patients with a normal and a high IAP, but mortality was higher among the latter (P =.02). CONCLUSIONS: Intra-abdominal hypertension is common after OLT and is significantly associated with renal failure, reduced urinary output, and intensive care unit mortality. It is, therefore, worth monitoring IAP in those undergoing OLT.

Abdomen↗

PubMed1996

Hypernatremia in hospitalized patients.

OBJECTIVE: To determine the incidence, clinical characteristics, and outcome for general medical-surgical hospital patients with hypernatremia. DESIGN: A prospective cohort study. SETTING: A 942-bed urban university hospital. PATIENTS: All patients who developed a serum sodium concentration of 150 mmol/L or greater during a 3-month observation period. MEASUREMENTS: Daily fluid balance, mental status, and serum and urine electrolytes and osmolality. RESULTS: 103 patients were identified. Eighteen patients were hypernatremic on hospital admission, and 85 developed hypernatremia during hospitalization. Patients who developed hypernatremia during hospitalization were younger than patients who developed hypernatremia before hospital admission (mean age +/- SD, 58.9 +/- 19.2 years compared with 76.6 +/- 16.6 years; P < 0.01) but did not differ in age from the patients of the general hospitalized population. Eighty-nine percent of patients who developed hypernatremia during hospitalization had urine concentrating defects, primarily as the result of the use of diuretics or of solute diuresis, whereas only 50% of patients who were hypernatremic on admission could be shown to have concentrating defects (P < 0.01). Fifty-five percent of all hypernatremic patients had increased insensible water losses, and 35% had increased enteral water losses. Eighty-six percent of patients with hospital-acquired hypernatremia lacked free access to water, 74% had enteral water intake of less than 1 L/d, and 94% received less than 1 L of intravenous electrolyte-free water per day during the development of hypernatremia. No supplemental electrolyte-free water was prescribed during the first 24 hours of hypernatremia in 49% of patients. The duration of hypernatremia was shorter in patients who were hypernatremic on admission (median duration, 3 days) than in patients with hospital-acquired hypernatremia (median duration, 5 days; P < 0.05). Mortality was 41% for all patients, but hypernatremia was judged to have contributed to mortality in only 16% of patients. CONCLUSIONS: Although the development of hypernatremia before hospital admission occurs primarily in geriatric patients, hospital-acquired hypernatremia was more common in our cohort and had an age distribution similar to that of the general hospitalized population. Hospital-acquired hypernatremia was primarily iatrogenic, resulting from inadequate and inappropriate prescription of fluids to patients with predictably increased water losses and impaired thirst or restricted free water intake or both. Treatment of hypernatremia is often inadequate or delayed. Efforts to manage hypernatremia better and altogether avoid hospital-acquired hypernatremia should focus on both physician education and the development of hospital systems to prevent errors in fluid prescription.

Adult↗

PubMed1999

Frequency, aetiology and outcome of hypernatraemia in hospitalised patients in Umtata, Transkei, South Africa.

OBJECTIVE: To study the frequency, aetiology and outcome of hypernatraemia in adult hospitalised patients. DESIGN: Retrospective hospital-based study of hypernatraemia using laboratory data to identify patients. OUTCOME MEASURES: Fluid intake, mortality, neurological signs and symptoms, serum sodium concentration. RESULT: The overall incidence of hypernatraemia was 1.4%. Among the 98 patients (mean age 44.6 years), head injury (30%), diabetes mellitus (22%), infection (13%) and gastro-intestinal disturbances (13%) were the principal aetiological conditions occurring in more than 75% of all hypernatraemic patients. Hypernatraemia was observed in both the young and the elderly. The overall mortality was high (56%), with significantly higher values in patients over the age of 44 years (66%) and those with serum sodium values greater than 165 mmol/L. Hospital-acquired hypernatraemia was more frequently (59%) observed than admission hypernatraemia (41%). Forty seven per cent of patients had no access to water, 31% were on diuretic therapy whilst solute diuresis was associated with hypernatraemia in 33%. Forty six per cent of patients were clinically dehydrated. Serum sodium levels normalised in more than half the patients (56%). Persistent hypernatraemia was associated with higher mortality. Though neurological signs and symptoms were observed in twelve per cent of patients, it was not associated with higher mortality. CONCLUSIONS: Hypernatraemia was observed in both the young and elderly and was associated with a high mortality. Hospital-acquired hypernatraemia was more frequently observed and was found to result from inadequate and inappropriate administration of fluids to patients with impaired thirst or restricted free water intake or both. Severe hypernatraemia appeared to be an indicator of poor prognosis.

Adult↗

PubMed1992

[Studies on the mechanism of action of angiotensin converting enzyme inhibitors on the dog kidney].

The effects of angiotensin-converting enzyme (ACE) inhibitors, rampipril, captopril and enalapril, on the renal circulation and function were examined in normotensive dogs, in relation to the renin-angiotensin-aldosterone (R-A-A) and kallikrein-kinin (K-K) systems and prostaglandins (PGs). These inhibitors markedly decreased renal vascular resistance (RVR) in parallel with a reduction in systemic blood pressure, and increased renal blood flow (RBF). Captopril exerted its effects rapidly, but its disappearance was also rapid. The onset of ramipril's effects was slightly delayed, but its antihypertensive and RVR-decreasing effects were fairly prolonged. Ramipril showed more potent and longer-lasting RBF-increasing effect and induced marked Na diuresis. Enalapril had no diuretic effect, and captopril's effect was only temporary. Plasma renin activity was increased similarly by the three inhibitors, but only ramipril significantly decreased plasma aldosterone concentration. This aldosterone secretion inhibition by ramipril may be partly involved in the diuretic effect. Involvement of the K-K system and PGs in ramipril's effects on the dog kidney was examined. When systemic PG biosynthesis was inhibited by indomethacin pretreatment, ramipril-induced increases in RBF and urine volume were inhibited about 50%. Inhibition of the K-K system by aprotinin pretreatment resulted in marked inhibition of urine volume increase, but scarcely affected RBF increase. These results indicate that ramipril produces the most potent effect on the renal circulation and function of the dog among the three ACE inhibitors and that its diuretic action is mostly due to kinins and kinin-induced PGs in the kidney and the RBF increase, due to the R-A-A system and PGs.

Angiotensin-Converting Enzyme Inhibitors↗