Reduction of K+ efflux in cultured mouse fibroblasts, by mutation or by diuretics, permits growth in K+-deficient medium.

The mouse fibroblastic cell line LM(TK-) is unable to grow at external K+ concentrations below a threshold value of 0.4 mM. At subthreshold K+ concentrations, LM(TK-) cells rapidly lose intracellular K+ and eventually lyse. We have analyzed the pathway primarily responsible for K+ efflux under these experimental conditions and reports its specific inhibition by two diuretics, furosemide and bumetanide. Bumetanide, an analog of furosemide, was a more potent inhibitor (by several orders of magnitude) than was furosemide itself. The effects of ouabain and bumetanide were additive, suggesting independence of diuretic-sensitive K+ efflux from Na+/K+ pump-mediated fluxes. Characterization of K+ efflux in LTK-5, a mutant derived from LM(TK-) and selected for its ability to grow at 0.2 mM K+ indicated that the mutant had lost the diuretic-sensitive K+ efflux pathway. Net cation fluxes, steady-state intracellular cation concentrations, and growth at reduced K+ concentrations were comparable for LM(TK-) cells maximally inhibited by diuretics and for the LTK-5 mutant grown either in the presence or absence of diuretics. Thus, reduction in K+ efflux, either by diuretic addition diuretics. Thus, reduction in K+ efflux, either by diuretic addition or by genetic alteration, can permit the cell to maintain normal cation gradients and to grow at otherwise subthreshold external K+ concentrations.     

Cardiac effects of piretanide and furosemide on intact anesthetized dogs and on isolated atria

The effects of piretanide and furosemide on systemic arterial blood pressure and heart rate were examined in the anesthetized dog and the effects on atrial rate and contractile force were assessed in isolated atrial muscle perfused with heparinized arterial blood from a donor dog. When piretanide was administered intravenously to intact dogs, the depressor and bradycardic responses were produced dose-dependently. There were no significant simultaneous chronotropic or inotropic changes in the isolated atrium. On the other hand, furosemide (1-3 mg/kg) did not induce significant changes in either systemic blood pressure or heart rate in the intact dog. The atrial rate and developed tension were also not affected in the isolated atrium. A potent beta-adrenoceptor blocking agent, propranolol (1 mg/kg i.v.), consistently produced a significant depressor response and a profound negative chronotropic effect in the intact dogs; significant negative chronotropic and inotropic effects were also observed in the isolated atrium. When large doses of piretanide and furosemide were injected intraarterially into the sinus node artery of the isolated atrium, atropine-insensitive negative chronotropic and inotropic effects were induced dose-dependently. The potency of the negative chronotropic effect of piretanide was slightly greater than that of furosemide, but the negative inotropic effect of piretanide was slightly smaller than that of furosemide. These data indicate that piretanide has a depressor effect without significant cardiac influences. However, a high dose of piretanide has negative chronotropic and inotropic effects. These effects were not observed with the doses of furosemide (1-3 mg/kg) employed in this study.     

Effect of inhaled furosemide and torasemide on bronchial response to ultrasonically nebulized distilled water in asthmatic subjects.

Inhaled furosemide has been shown to reduce the bronchoconstriction induced by several indirect stimuli, including ultrasonically nebulized distilled water (UNDW). Because the protective effect could be due to the inhibition of the Na(+)-2Cl(-)-K+ cotransport system of bronchial epithelium, we have compared the protective effect of inhaled furosemide with that of inhaled torasemide, a new and more potent loop diuretic, on UNDW-induced bronchoconstriction in a group of 12 asthmatic subjects. UNDW challenge was performed by constructing a stimulus-response curve with five increasing volume outputs of distilled water (from 0.5 to 5.2 ml/min) and the bronchial response expressed as the provocative output causing a 20% fall in FEV1 (PO20UNDW). On different days, each subject inhaled an equal dose (28 mg) of furosemide and torasemide in a randomized, double-blind, placebo-controlled study 5 min prior to an UNDW challenge. Furosemide and torasemide had no significant effect on resting lung function. The geometric mean value of PO20UNDW measured after placebo was 1.73 ml/min. This was significantly lower than that recorded after furosemide (4.25 ml/min; p < 0.025), but not after torasemide (3.05 ml/min; p = 0.07). Inhaled furosemide totally blocked bronchial response to UNDW in five subjects. In two of five subjects the response was also blocked by inhaled torasemide. A remarkable increase in diuresis was noted only after torasemide in most subjects. We conclude that inhaled furosemide has a better protective effect than does inhaled torasemide against UNDW-induced bronchoconstriction. However, the protective effect of furosemide is variable, with some asthmatic patients showing no change in bronchial response to UNDW.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of furosemide on renal excretion of oxypurinol and purine bases

To examine whether furosemide affects the plasma concentration and urinary excretion of purine bases and oxypurinol, we administered allopurinol (300 mg) orally to 6 healthy subjects and then administered furosemide (20 mg) intravenously 10 hours later. Furosemide (20 mg) decreased the urinary excretion of uric acid by 40% (P < .01), oxypurinol by 39% (P < .05), and xanthine by 43% (P < .05) and the fractional clearance of uric acid by 45% (P < .01) and oxypurinol by 34% (P < .05) when measured 1 to 2 hours after administration. Moreover, furosemide increased the plasma concentration of uric acid by 6% at 1.5 hours after administration. These results indicate that furosemide may decrease the urinary excretion of uric acid and oxypurinol by acting on their common renal transport pathway(s). In addition, it is suggested that the effect of furosemide on oxypurinol is clinically important, since the hypouricemic effect of allopurinol may become more potent as a result.     

Long-term furosemide treatment in idiopathic edema

Of 12 patients with idiopathic edema, ten patients had received total doses of furosemide of up to about 950 g. A good negative correlation was observed between the creatinine clearance and the duration of daily oral furosemide intake of more than 40 mg, and a highly significant correlation was found between the logarithm of the creatinine clearance and the duration of daily furosemide ingestion. Cessation of furosemide and institution of a sodium-restricted diet was followed by improvement in the creatinine clearance. Three patients had acute renal failure with myoglobinuria. All patients examined showed tubular and/or interstitial changes. This study shows that in idiopathic edema, long-term furosemide treatment gradually impairs renal function, with reversal to a considerable degree after cessation of the drug, and that it causes organic changes in the kidney.     

Furosemide and plasma renin activity in essential hypertension.

Changes in arterial blood pressure, renal electrolyte excretion, and plasma renin activity in response to repeated doses of furosemide were measured in 12 patients with essential hypertension admitted to the medical service for electrolyte balance studies. Eighty and 120 mg/day furosemide in divided doses for 5 to 10 days produced a prompt increase in renal sodium excretion. Urinary Na/K concentration ratios, which were elevated during peak natriuresis, returned to control levels following the initial diuretic response. In 2 patients with high initial levels of plasma renin activity, arterial blood pressure was not reduced by furosemide, and more potent antihypertensive agents were required to control the blood pressure. In the remaining patients, furosemide produced a significant decrease in systolic and diastolic blood pressure. There was a general upward shift of plasma renin levels in terms of 24-hour renal sodium excretion in those who demonstrated an antihypertensive response to the drug. However, the average increase in plasma renin activity after repeated doses of furosemide was not statistically significant and no correlation was demonstrated between the level of plasma renin activity after furosemide and the blood pressure lowering effect of the drug.     

Interaction of furosemide with serum thyroxine-binding sites: in vivo and in vitro studies and comparison with other inhibitors

The diuretic furosemide inhibits serum protein binding of T4 in equilibrium dialysis, dextran-charcoal, and competitive ligand binding separation systems and displaces [125I]T4 from isolated preparations of T4-binding globulin (TBG), prealbumin, and albumin. Equilibrium dialysis studies of undiluted normal serum showed that about 10 micrograms/ml furosemide increased the free T4 and free T3 fractions. Displacement occurred at lower drug concentrations in sera with subnormal albumin and TBG levels. Binding of [14C]furosemide to TBG was inhibited by unlabeled T4, suggesting that furosemide and T4 share a common binding site. A single oral dose of 500 mg furosemide given to five patients maintained on peritoneal dialysis increased the percentage of charcoal uptake of [125I]T4 (using serum diluted 1:10) from 4.1 +/- 1.0 (+/- SE) to 10.8 +/- 4.3 (P less than 0.01) after 2 h, while decreasing total T3 from 75 +/- 5 to 56 +/- 13 ng/dl (P less than 0.01) and total T4 from 6.7 +/- 0.9 to 4.8 +/- 0.8 micrograms/dl (P less than 0.01) after 5 h. Various ligands inhibited [125I]T4 binding to serum proteins in the following relative molar relationship: T4, 1; furosemide, 1.5 X 10(3); fenclofenac, 2 X 10(4); mefenamic acid. 2.5 X 10(4); diphenylhydantoin, 4 X 10[4); ethacrynic acid, 10(5); heparin 5 X 10(5); 2-hydroxybenzoylglycine, 10(6); and sodium salicylate, 1.5 X 10(6). These studies demonstrate that furosemide competes for T4-binding sites on TBG, prealbumin, and albumin, so that a single high dose can acutely lower total T4 and T3 levels. The drug is much more potent on a molar basis than other drug inhibitors of T4 binding, but at normal therapeutic concentrations, furosemide is unlikely to decrease serum T4 or T3. However, high doses, diminished renal clearance, hypoalbuminemia, and low TBG accentuate its T4- and T3-lowering effect. Hence, furosemide should be considered a possible cause of low thyroid hormone levels in patients with critical illness. The significance of this drug in reports of impaired hormone and drug binding in renal failure requires further assessment.     

Unchanged extraction of atrial natriuretic factor across the chronic ischemic human kidney.

The extractions of atrial natriuretic factor (EANF) and the glomerular filtration marker 51Cr-ethylenediamine tetraacetic acid (EEDTA) were determined before and after intravenous injection of furosemide across each of the two kidneys during renal vein catheterization in hypertensive patients with unilateral or bilateral renovascular disease. Before administration of furosemide, EANF was approximately 55% across both the more and the less affected kidney while EEDTA was significantly decreased across the more affected kidney. Significant lateralization of renin secretion to the more affected kidney was found, demonstrating an enhanced ipsilateral formation of renin. Administration of furosemide caused a significant decrease in EEDTA across the less affected kidney while the ipsilateral EANF did not change. Furosemide caused no change in EEDTA or EANF across the more affected kidney. No significant correlations were found between EANF and EEDTA. These results demonstrate that the extraction of ANF is unchanged across the chronic ischemic human kidney. Furthermore, in the single kidney, changes in EEDTA, as induced by furosemide, are not related to changes in ipsilateral EANF. Since the relation between simultaneously determined single kidney extractions of ANF and 51Cr-EDTA reflects the relation between the single kidney clearance of ANF and the ipsilateral glomerular filtration rate, our data indicate a dissociation between changes in the single kidney glomerular filtration rate and the ipsilateral total renal clearance of ANF.     

Acute generalized exanthematic pustulosis (AGEP) in a patient treated with furosemide

BACKGROUND: Although they appear more rarely than electrolyte disturbances, cutaneous reactions are important adverse effects of furosemide. This is particularly true for bullous skin eruptions, because they may be life-threatening. CASE REPORT: We describe a patient who developed acute generalized exanthematic pustulosis (AGEP) during treatment with furosemide. Because the patient had developed similar skin eruptions during treatment with furosemide years before, furosemide was considered the most likely cause of this reaction. The short period of time between exposure to furosemide and the appearance of the skin reaction, as well as a positive lymphocyte transformation test, suggest an immunological mechanism of the skin disease. CONCLUSION: AGEP is a possible cutaneous side effect of furosemide.     

The effect of furosemide during normoxemia and hypoxemia

The effect of furosemide infusion was studied in 6 normal subjects and 6 patients with severe COPD and right ventricular failure during normoxemia and hypoxemia. In normal subjects, hypoxemia alone caused an insignificant (p less than 0.15) fall in plasma aldosterone concentrations (PAC). Intravenously administered furosemide resulted in significant (p less than 0.05) increases in PAC during both normoxemia and hypoxemia. After furosemide treatment mean arterial pressure (MAP) was significantly lower and arginine vasopressin (AVP) was significantly higher (p less than 0.05) with hypoxemia than with normoxemia. These changes in MAP and AVP were strongly correlated (r = -0.84). Urinary losses of water and sodium were similar after furosemide treatment with hypoxemia and normoxemia. In patients with right ventricular failure, neither changes in oxygenation nor furosemide infusion affected the markedly elevated baseline PRA and PAC levels. Arginine vasopressin levels were significantly higher with hypoxemia than with normoxemia, but urinary losses of water and salt did not differ between the 2 study days. We conclude that hypoxemia does not affect the PAC increase or urinary volume and sodium response to furosemide.     

Effects of furosemide on hemodynamic, electrocardiographic, and symptomatic responses to exercise in patients with angina pectoris (author's transl)

In 12 patients with coronary artery disease and typical exercise-induced angina pectoris hemodynamic and ECG studies were performed at rest and during ergometer load in supine position. During the attacks of angina there was a significant ST-depression in all cases accompanied by elevated pulmonary capillary wedge pressures (PCP) and pulmonary artery mean pressures (PAM). Intravenous administration of 40 mg furosemide showed consistent hemodynamic changes. Cardiac output (CO) dropped significantly by 15.9 per cent at rest (p is less than 0.001) and by 6.9 per cent during exercise (p is less than 0.005). The PCP during exercise following furosemide decreased from 32.9 mmHg to 11.8 mm Hg (p is less than 0.001) and was paralleled by a significant decrease of PAM, indicating reduction of ischemia-related hemodynamic impairment. Furthermore, there was a striking improvement of Ecg findings during ergometer load in 9 of 12 patients as well as a relief of anginal pain in 11 of 12 patients. The present demonstration of antianginal properties of furosemide may be explained by the reduction of ventricular volumes and pressures, resulting in a decrease of myocardial wall stress. These effects are suggested to be related to the peripheral venodilator capacity of furosemide in conjunction with its diuretic properties. Thus, in patients with left ventricular dysfunction secondary to ischemia, intravenous furosemide may have salutary effects on myocardial oxygen requirements resembling the action of nitroglycerin, but without its oxygen-wasting effects on tachycardia.     

Regulation of Renal Na-K-Cl Cotransporter NKCC2 by Humoral Natriuretic Factors: Relevance in Hypertension

A furosemide-sensitive Na-K-Cl cotransporter (NKCC2 isoform) accounts for almost all luminal NaCl reabsorption in the thick ascending limb of Henle's loop (TALH). The activity of this transport protein is regulated by humoral factors (CIF: cotransport inhibitory factors). One family of CIF compounds is represented by the urinary phytoestrogens equol and genistein, which inhibit cotransport fluxes at similar concentrations as furosemide. Moreover, they possess similar salidiuretic potency as furosemide in the isolated perfused rat kidney, but are less potent than furosemide in vivo.Thus, dietary phytoestrogens can be responsible, at least in part, for the low blood pressure of vegetarians. A second type of CIF is represented by a circulating and urinary factor which is evoked by salt-loading. This, which is not a “ouabain-like” factor, appears to be a new retropituitary natriuretic compound. Endogenous CIF is increased in hypertensive Dahl salt-sensitive rats, probably as a compensatory mechanism against the enhanced NaCl reabsorption in the TALH, which characterizes this model of hypertension. Finally, chronic excess of circulating CIF inhibits and induces up-regulation of erythrocyte Na-K-Cl cotransporter NKCC1     

Effects of acute metabolic acid-base changes and furosemide on magnesium excretion in rats

The effect of acute metabolic acid-base changes on renal magnesium transport is not well defined. We have examined renal magnesium handling in three groups of ten acutely thyroparathyroidectomized rats infused with isotonic NaCl (controls), NH4Cl (acidosis), and NaHCO3 (alkalosis). To define the interactions of furosemide with acid-base changes and in an attempt to localize the site of action of acidosis and alkalosis on tubular magnesium transport, the rats were studied in a second phase after administration of a maximal dose of furosemide. Before furosemide, the blood pH was 7.40 in the controls, 7.27 (P less than 0.001) in the acidotic rats, and 7.56 (P less than 0.001) in the alkalotic rats. The filtered magnesium load was not significantly different in the three groups, but fractional excretion of magnesium (FEMg) was 33.7%, 37.4%, and 13.3% in the controls, the acidosis group, and the alkalosis group, respectively. Following furosemide, the blood pH was unchanged in each group, but FEMg increased significantly to 55.4%, 71.1% (P less than 0.01 compared with controls), and 41.4% (P less than 0.01 compared with controls) in the controls, the acidotic rats, and the alkalotic rats, respectively. These data indicate that metabolic alkalosis per se enhances renal magnesium transport, and this effect is also evident after blockade of loop magnesium reabsorption by a maximal dose of furosemide. Acidosis per se does not significantly alter magnesium transport, but an inhibitory effect of acidosis on magnesium reabsorption becomes evident when distal magnesium delivery is greatly increased by furosemide. These interactions suggest that metabolic acid-base changes and furosemide may influence magnesium reabsorption at different tubule sites.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lack of correlation between two methods for the assessment of salt sensitivity in essential hypertension

The existence of a heterogeneous blood pressure (BP) response to salt intake, a phenomenon known as salt sensitivity, has increasingly become a subject of clinical hypertension research, and has important clinical and prognostic implications. However, two different methodologies are currently used to diagnose salt sensitivity. The aim of the present study was to compare the BP response to intravenous sodium load and depletion on the one hand, and to changes in dietary salt intake on the other, in order to assess salt sensitivity in a group of essential hypertensive patients. Twenty-nine essential hypertensives underwent two different procedures separated by 1 month: a dietary test consisting of a 2-week period of low (20 mmol/day) and high (260 mmol/day) salt intakes, and an intravenous test consisting of a 2 litre saline load over a 4-h period, followed by 1 day of low (20 mmol) salt intake and furosemide (40 mg/8 h orally) administration. BP was registered at the end of every period using 24-h ambulatory BP monitoring. In the whole group of hypertensive patients studied, both low salt intake and furosemide administration significantly (P < 0.01) decreased mean BP. Correlation coefficients of BP changes obtained using the two methodologies were between 0.3 and 0.4. Moreover, coefficients of agreement between the oral and the intravenous tests, using several cut points for BP changes, were systematically below 0.5, thus indicating a misclassification of salt sensitivity greater than 50%, depending on the method used. None of the cut points for BP changes during furosemide administration showed a good combination of sensitivity and specificity compared with changes in response to low dietary salt. The present results indicate that the diagnosis of salt-sensitive hypertension should be based on the BP response to changes in dietary salt intake, while BP response to saline and furosemide administration leads to a systematic misclassification of more than 50% of patients, even using different cutpoints for changes in BP.     

Hemodynamic comparison of primary venous or arteriolar dilatation and the subsequent effect of furosemide in left ventricular failure after acute myocardial infarction

The hemodynamic effect of venous dilatation (intravenous isosorbide dinitrate [ISDN]) and arteriolar dilatation (intravenous hydralazine), both as firstline treatment and then combined with intravenous furosemide, were evaluated in a randomized, between-group comparison in 20 men with severe acute left-sided cardiac failure after myocardial infarction (MI). Both ISDN (50 to 200 micrograms/kg/hour) (Group 1) and hydralazine (0.15 mg/kg) (Group 2) reduced systemic arterial pressure (p less than 0.05) and vascular resistance (p less than 0.05). Pulmonary artery occluded pressure was reduced (p less than 0.01) only by ISDN, whereas heart rate (p less than 0.01), cardiac output (p less than 0.01) and stroke volume (p less than 0.05) were increased only after hydralazine. After ISDN, furosemide (1 mg/kg) decreased left-sided cardiac filling pressure by 1 mm Hg (p greater than 0.05), whereas after hydralazine, furosemide in a similar dose reduced pulmonary artery occluded pressure by 5 mm Hg (p less than 0.01). In both groups of patients, furosemide transiently increased systemic arterial pressure (p less than 0.05). Cardiac output was reduced (p less than 0.05) and systemic vascular resistance increased (p less than 0.05) in Group 1 patients after furosemide. Similar changes in both variables in Group 2 patients did not attain statistical significance. In conclusion, ISDN-induced venous dilatation is preferable to primary arteriolar dilatation by hydralazine as first-line treatment in acute left-sided cardiac failure. However, hydralazine and furosemide in combination were equally effective in reducing pulmonary artery occluded pressure and increasing cardiac output. The influences of each regimen on prognosis await further investigation.     

Furosemide effects in patients with chronic renal insufficiency

In 8 patients with a slight restriction of the renal function (serum creatinine 150-300 mumol/l), 10 patients with a severe restriction of the renal function (serum creatinine greater than 300-1,200 mumol/l) and in 10 control persons with intact renal function on 2 subsequent days after 40 and 80 mg furosemide the pharmacokinetic data were calculated intravenously from the course of the serum concentration and the renale excretion as well as pharmacodynamic parameters. In comparison to the control persons in patients with creatinine values of more than 200 mumol/l still 4 hours after intravenous injection furosemide could be proved in the serum. According to this the excretion of the unchanged furosemide was clearly decreased in the 24-hour-urine. In decreased renal clearance of furosemide the elimination half-life period was prolonged. In all three groups of patients the diuretic effect of furosemide was very distinctly marked in the first four hours after injection of 40 mg, a doubling of the dose did not increase this effect. Only in the first four hours also an increased excretion of sodium, chloride and calcium occurred; in the 24-hour-collection period no differences between the three groups were the result. The excretion of creatinine and urea-N in the urine was not influenced by furosemide. Thus also in the chronic renal insufficiency there is the indication of the furosemide therapy only then, when the extracellular space or the intravasal volume are enlarged. As individual dose 40 mg are recommended intravenously.     

Thiazide diuretics do not potentiate cAMP response to parathyroid hormone.

We evaluated the hypothesis that thiazide-induced hypercalcemia reflects potentiation of the cAMP response to parathyroid hormone (PTH) consequent to inhibition of phosphodiesterase in bone and kidney. A panel of thiazide diuretics did inhibit low-Km phosphodiesterase activity from bone homogenates. However, furosemide, a nonthiazide diuretic that does not promote calcium retention, was more potent a phosphodiesterase inhibitor than either chloro- or hydrochlorothiazide (CTZ, HCTZ). Thiazides did not influence basal or PTH-stimulated cAMP levels in incubated calvaria or renal cortical slices. Administration of CTZ or HCTZ to rats for 4 days did not affect basal cAMP, nor did such treatment potentiate the cAMP response in Calvaria to infusion of parathyroid extract in vivo. CTZ, HCTZ, and furosemide increased basal adenylate cyclase from renal cortex but did not affect PTH-stimulated activity. Adenylate cyclase from bone was not affected by thiazides but was inhibited by furosemide. Thiazide treatment potentiated the calcemic response to parathyroid extract in vivo but did not affect the calcemic response to dibutyryl cAMP. We conclude that potentiation of the cAMP response to PTH does not underlie the unique effects of thiazides on calcium metabolism.     

The rational use of diuretics in the treatment of arterial hypertension.

The development of modern pharmacologic diuretic agents has revolutionized the therapy of arterial hypertension. The diuretics currently available are easily administered orally, are effective in the presence of alkalosis or acidosis, are non-toxic and have a low incidence of side effects which are readily circumvented or treated. Loop diuretics such as furosemide have the capacity to be effective in patients with diminished renal function or clinical situations that have a powerful stimulus to sodium retention. In clinical circumstances when renal potassium loss is to be prevented such as in patients receiving digitalis, the addition of a potassium-sparing diuretic to either a thiazide or furosemide will achieve the clinical goal of providing an effective diuresis while inhibiting potassium excretion. The mechanism of antihypertensive activity of the diuretic agents appears to be the reduction of extracellular fluid volumes and plasma volumes. Hence, the clinical dictum that to be effective as an antihypertensive agent, diuretics should be administered in diuretic doses. Besides being the cornerstone of initial antihypertensive therapy, diuretics also play an important role in antihypertensive therapy of patients with moderate to severe hypertension who are receiving potent antihypertensive drugs of the vasodilator or sympatholytic class of compounds. Indeed, one of the most important steps in the successful therapy of these patients receiving multiple drugs, is the re-assessment of the diuretic agent. The sodium retention and consequent fluid volume expansion associated with the administration of these potent antihypertensive agents may often cause these patients to develop apparent drug resistance since the thiazide diuretics are not potent enough to counteract the powerful stimulus to sodium retention caused by these antihypertensive agents. The re-evaluation of the diuretic agent at this point will usually necessitate the substitution of furosemide for thiazide or the doubling of the dose of the present loop diuretic. A working knowledge of the physiology of urine formation and the sites of action of currently available diuretic agents will enable the clinician to tailor the diuretic agent to the clinical circumstances of an individual patient and allow the clinician to rationally select a diuretic for the treatment of arterial hypertension.     

Responses of aldosterone-producing adenomas to ACTH and angiotensins.

To elucidate the control mechanism of aldosterone production in primary aldosteronism, in vivo and in vitro studies were done in 7 patients with aldosterone-producing adenomas. In the in vivo study, plasma aldosterone was stimulated more significantly by (Formula: see text), synthetic ACTH than by angiotensin II or furosemide. Diurnal variations of plasma aldosterone, which were studied in 4 patients, were similar to those seen in normal controls. In agreement with the results in the in vivo study, the in vitro study also revealed ACTH stimulated aldosterone and deoxycorticosterone (DOC) from the adenoma more markedly than angiotensin II or III. There was no adenoma which was more sensitivie to angiotenion II or III than to ACTH. From these results it is considered that changes in plasma aldosterone induced by the exogenous administration of angiotensin II or ACTH in patients with aldosterone-producing adenoma are mainly based on changes in aldosterone production in the adenoma. Furthermore, in patients with an aldosterone-producing adenoma in whom diurnal variations of plasma aldosterone similar to those in normal subjects are observed, responses of aldosterone to angiotensin II are supposed to be less than those to ACTH.