Effects of Ethacrynic Acid (a New Saluretic Agent) on Renal Diluting and Concentrating Mechanisms: Evidence for Site of Action in the Loop of Henle*

Goldberg, Martin; McCurdy, Donna K.; Foltz, Elwood L.; Bluemle, Lewis W.

doi:10.1172/jci104905

Cited by 155 publications

(48 citation statements)

References 25 publications

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“…These studies were designed to evaluate both of these variables under conditions of increased delivery of sodium to the loop of Henle with and without volume expansion. Since TCH20 is a function of the rate of medullary sodium accumulation during hydropenia, and CH2O is an index of the rate of sodium removal from tubular fluid at water-impermeable sites, then changes in both of these variables reflect changes in sodium transport in the loop of Henle (20).…”

Section: Studies During Water Diuresismentioning

confidence: 99%

Mechanism of exaggerated natriuresis in hypertensive man: impaired sodium transport in the loop of henle

Buckalew¹,

Puschett²,

Kintzel³

et al. 1969

J. Clin. Invest.

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A B S T R A C T To evaluate the effects of saline loading on distal sodium reabsorption in hypertensive man, studies were performed during both water deprivation and water diuresis in eight hypertensive subjects, and the results were compared to data obtained from similar studies in normal subjects. All hypertensive patients exhibited an enhanced excretion of filtered sodium (Ca/CIn) at any level of distal delivery of sodium compared to normal controls. Free water reabsorption (TCH2o) during hypertonic saline loading was quantitatively abnormal in the hypertensives at high levels of osmolar clearance (Co.m), and also the curve of TCHIo vs. Co.m leveled off above a Co.m of 18 ml/min per 1.73 m' in the hypertensive group in contrast to the normal controls in whom TCH,0o showed no evidence of achieving an upper limit. Sodium depletion exaggerated the abnormality in T'Ho in hypertensives, and resulted in a positive free water clearance (CH2o) during hydropenia.During hypotonic saline loading in water diuresis, changes in free water clearance per 100 ml of glomerular filtrate (CIo0/CI.) were less at any given increment in urine flow per 100 ml of glomerular filtrate (V/CG.) in the hypertensives compared to normal controls (P < 0.001). This abnormality in CH2o/CI. in the hypertensives in conjunction with the defect in T'H2o observed during hydropenia indicates that sodium reabsorption in the loop of Henle was abnormal at any given rate of distal delivery of sodium in hypertension. Furthermore, these abnormalities in TCH2o and CH20 coincided temporally with the development of the exaggerated natriuresis. Although the distal defect in sodium transport, in large part, accounted for the augmented natriuresis in hyperThis work was presented in part at the 1st Annual Meeting of the

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Section: Studies During Water Diuresismentioning

confidence: 99%

Mechanism of exaggerated natriuresis in hypertensive man: impaired sodium transport in the loop of henle

Buckalew¹,

Puschett²,

Kintzel³

et al. 1969

J. Clin. Invest.

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“…The drug depresses free water formation during maximal water diuresis in man (4) and dog (5). It also abolishes the renal concentrating ability since free water reabsorption (TCH20)1 is reduced to nearly zero (4).…”

Section: Introductionmentioning

confidence: 99%

Effects of Ethacrynic Acid on the Isolated Collecting Tubule

Abramow¹

1974

J. Clin. Invest.

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A B STRACT Effects of the diuretic ethacrynic acid on osmotic water permeability were investigated in the isolated perfused collecting tubule of the rabbit kidney.The base-line water permeability of the collecting tubule was not affected when the drug (10-'M) alone was added to the bathing medium. Vasopressin alone in the bathing medium (2, 5 AU/ml) elicited a significant increase in osmotic water absorption. With vasopressin kept in the bathing medium, the addition of 10-'M ethacrynic acid depressed the hydro-osmotic effect of vasopressin by 50%. This inhibitory effect of low concentrations of ethacrynic acid could be surmounted by high, supramaximal dosage levels of vasopressin.When 10-4M ethacrynic acid was added to the bathing medium before vasopressin, the hydro-osmotic effect of vasopressin and the diuretic in combination was insignificant.Dibutyryl adenosine 3'5'-monophosphate (10-4-10-'M) alone in the bathing medium significantly increased baseline osmotic water flow, mimicing the effect of antidiuretic hormone. When ethacrynic acid was added together with the nucleotide, the permeability remained at the same high level. Theophylline, like the nucleotide and vasopressin, produced a significant hydro-osmotic effect. The magnitude of this responise was not affected by further addition of ethacrynic acid (10-4`\).It was concluded that ethacrynic acid is an antagonist of antidiuretic hormone. The antagonism probably occurs at the level of the receptor site of the hormone on the peritubular membrane. Antagonism to circulating antidiuretic hormone may therefore be one of the factors involved in the loss of renal concentrating ability brought about by ethacrynic acid diuresis.

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“…Ethacrynic acid (2 mM) was used in addition to ouabain as an inhibitor of (~a + , ~' t d e p e n d e n t ATPase (23). Ethacrynic acid has been shown to inhibit Na+ absorption in the Loop of Henle (18) and in hamster intestine (8) and to inhibit the extrusion of Na+ from guinea pig kidney cortex slices (23). All inhibitors tested inhibited L-leucine and D-galactose uptake at least 50% after a 30-min preincubation 5 …”

Section: Intestine Of 2-day-old Rats1mentioning

confidence: 99%