Effect of furosemide on sodium reabsorption by proximal tubule of the dog

Knox, FG; Wright, Fay; Ss, Howards; Berliner, Robert W.

doi:10.1152/ajplegacy.1969.217.1.192

Cited by 63 publications

(32 citation statements)

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“…Hence, Cirksena, and associates (3) discounted the influence of acutely reduced GFR on proximal reabsorption in their acute caval obstruction experiments. However, recent work both in dogs (4,5) and in rats (6,7) demonstrates that proximal fractional reabsorption is in fact enhanced when GFR is acutely reduced. Thus, it seemed likely that acute caval obstruction and saline loading had opposing effects on proximal reabsorption.…”

Section: Methodsmentioning

confidence: 99%

“…They concluded that renal sodium retention in acute caval dogs is due to altered proximal reabsorption and suggested that this mechanism may be important in chronic edematous states. Acute obstruction of the vena cava produces marked systemic and renal hemodynamic changes (1, 3) which in themselves have been shown to increase proximal fractional reabsorption (4)(5)(6)(7). No direct evaluation of the separate effect of such hemodynamic changes was possible from the studies of Cirksena et al (3), since observations were made only after the combination of caval obstruction and saline infusion, but not after caval obstruction alone.…”

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confidence: 99%

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Proximal tubular function in dogs with thoracic caval constriction

Rb¹,

Alexander²,

Ng³

1971

J. Clin. Invest.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Proximal tubular function in dogs with thoracic caval constriction

Rb¹,

Alexander²,

Ng³

1971

J. Clin. Invest.

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“…In dogs, furosemide did not affect proximal tubular sodium reabsorption, yet decreased GFR. Meanwhile, furosemide inhibited the reabsorption of a saline drop in the proximal tubule so that the decrease in GFR might have obscured the effects of furosemide on proximal tubular reabsorption (86). Micropuncture experiments in dogs (39) and monkeys (12) do not show diminished proximal tubular reabsorption during short-term furosemide administration.…”

Section: F961mentioning

confidence: 99%

Everything we always wanted to know about furosemide but were afraid to ask

Huang

Mees

Vos

et al. 2016

American Journal of Physiology-Renal Physiology

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Huang X, Dorhout Mees E, Vos P, Hamza S, Braam B. Everything we always wanted to know about furosemide but were afraid to ask. Am J Physiol Renal Physiol 310: F958 -F971, 2016. First published February 24, 2016 doi:10.1152/ajprenal.00476.2015.-Furosemide is a widely used, potent natriuretic drug, which inhibits the Na ϩ -K ϩ -2Cl Ϫ cotransporter (NKCC)-2 in the ascending limb of the loop of Henle applied to reduce extracellular fluid volume expansion in heart and kidney disease. Undesirable consequences of furosemide, such as worsening of kidney function and unpredictable effects on sodium balance, led to this critical evaluation of how inhibition of NKCC affects renal and cardiovascular physiology. This evaluation reveals important knowledge gaps, involving furosemide as a drug, the function of NKCC2 (and NKCC1), and renal and systemic indirect effects of NKCC inhibition. Regarding renal effects, renal blood flow and glomerular filtration rate could become compromised by activation of tubuloglomerular feedback or by renin release, particularly if renal function is already compromised. Modulation of the intrarenal renin angiotensin system, however, is ill-defined. Regarding systemic effects, vasodilation followed by nonspecific NKCC inhibition and changes in venous compliance are not well understood. Repetitive administration of furosemide induces short-term (braking phenomenon, acute diuretic resistance) and long-term (chronic diuretic resistance) adaptations, of which the mechanisms are not well known. Modulation of NKCC2 expression and activity in kidney and heart failure is ill-defined. Lastly, furosemide's effects on cutaneous sodium stores and on uric acid levels could be beneficial or detrimental. Concluding, a considerable knowledge gap is identified regarding a potent drug with a relatively specific renal target, NKCC2, and renal and systemic actions. Resolving these questions would increase the understanding of NKCCs and their actions and improve rational use of furosemide in pathophysiology of fluid volume expansion. extracellular fluid volume; natriuresis; renal function; chronic kidney disease; heart failure DIURETICS BLOCKING THE Na ϩ -K ϩ -2Cl Ϫ cotransporter (NKCC) have an important place in the treatment of fluid overload, specifically in the context of kidney disease and heart failure (64). Of the drugs that inhibit the NKCC2 in the loop of Henle (furosemide, bumetanide, torsemide, ethacrynic acid), furosemide is most commonly applied (66) and Ͼ40 million prescriptions are dispensed every year in the USA (66a). However, many uncertainties remain about intrarenal and systemic actions of furosemide, including its two main targets NKCC1 and NKCC2.Clinically, there are a number of undesirable consequences of the use of furosemide, of which the pathophysiological mechanisms have not been sufficiently investigated. Furosemide has been associated with worsening of kidney function in patients treated for volume overload admitted for acute heart failure (104) and even glomerular filtration rate (GFR) ...

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“…18-22]. Among studies demonstrating inhibition of proximal transport by F, some were complicat ed by hemodynamic changes [23][24][25] and body fluid de rangements [26,27], Others describe technical problems with collection [28]. In order to avoid inappropriate infu sion rates that may have been responsible either of dehydra tion or overexpansion in other studies, our own experiments were performed with the technique of urine reinfusion.…”

Section: Discussionmentioning

confidence: 99%

Microinjection Studies on the Effect of Furosemide on the Rat Nephron

Romano¹,

Federico²,

Favret³

et al. 1997

Kidney Blood Press Res

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The tubular site of furosemide (F) action was studied by the technique of diuretic microinjection (MIJ) into proximal tubules of the rat nephron. F was injected into the last proximal superficial loop of 51 proximal tubules, at the concentration of 3 · 10^-4 mol/l in an infusate that contained ¹⁴C-inulin. Collections were performed at the early distal tubule before and after MIJ. Single nephron filtration rate (SNGFR) remained unchanged, while the percent of filtered volume reabsorbed up to the site of collection was 85 ± 2 before, 79 ± 2% after MIJ, p < 0.005. The calculated concentration of F in the collected distal tubular fluid during the post-MIJ measurements averaged 3 · 10^-5 mol/l. This experiment was repeated by injecting F into the early proximal convolutions of 43 nephrons, while the collections were performed at the last proximal segments. In these studies of proximal volume absorption, SNGFR was 34 ± 3 before, 35 ± 4 nl/min after F (p > 0.6). The respective percent reabsorptions were 70 ± 3 and 73 ± 3% (p ± 0.3). In order to determine whether the technique per se was suitable to detect changes in reabsorption, the proximal MIJ study was repeated by using the carbonic anhydrase inhibitor dichlorphenamide 3 · 10^-5 mol/l in the microinjectate: while SNGFR remained unchanged, percent reabsorption fell from 63+5 to 45 ± 7% during injection of the diuretic, p < 0.03. We conclude that the technique is adequate to examine the effects of drugs, and that F does not reduce proximal volume absorption at concentrations of 3 · 10^-5 mol/l. The loop diuretic decreases distal volume absorption by abolishing the osmotic gradient between blood and tubular fluid along the early distal convoluted tubule.

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Effect of furosemide on sodium reabsorption by proximal tubule of the dog

Cited by 63 publications

References 0 publications

Proximal tubular function in dogs with thoracic caval constriction

Proximal tubular function in dogs with thoracic caval constriction

Everything we always wanted to know about furosemide but were afraid to ask

Microinjection Studies on the Effect of Furosemide on the Rat Nephron

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