The Site of Action of Furosemide

Romano, Giulio; Favret, G; Federico, Edda; Bartoli, Ettore

doi:10.1006/phrs.1998.0311

Cited by 22 publications

(28 citation statements)

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“…Second, furosemide and torsemide, but not bumetanide, have been shown to reduce absorption by the NaCl cotransport mechanism in the rat early DCT using the in vivo microperfusion technique (27) and to reduce Na ϩ entry into DCT cells by electron microprobe analysis (3). Third, some proximal micropuncture studies have demonstrated a reduction in proximal tubule fluid transport after intravenous furosemide, but this has not been a consistent finding (23). The proximal tubule effect has been suggested to result from furosemide-mediated inhibition of carbonic anhydrase.…”

Section: Discussionmentioning

confidence: 96%

Mouse model of type II Bartter's syndrome. I. Upregulation of thiazide-sensitive Na-Cl cotransport activity

Cantone¹,

Yang²,

Yan³

et al. 2008

American Journal of Physiology-Renal Physiology

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ROMK-deficient ( Romk−/−) mice exhibit polyuria, natriuresis, and kaliuresis similar to individuals with type II Bartter's form of hyperprostaglandin E syndrome (HPS; antenatal Bartter's syndrome). In the present study, we utilized both metabolic and clearance studies to define the contributions of specific distal nephron segments to the renal salt wasting in these mice. The effects of furosemide, hydrochlorothiazide, and benzamil on urinary Na+ and K+ excretion in both wild-type ( Romk+/+) and Romk−/− mice were used to assess and compare salt transport by the Na+-K+-2Cl− cotransporter (NKCC2)-expressing thick ascending limb (TAL), the Na+-Cl− cotransporter (NCC)-expressing distal convoluted tubule (DCT1/DCT2), and the epithelial Na+ channel (ENaC)-expressing connecting segment (CNT) and collecting duct (CD), respectively. Whole kidney glomerular filtration rate was reduced by 47% in Romk−/− mice. Furosemide-induced increments in the fractional excretion rate of Na+ and K+ and absolute excretion of Na+ and K+ were significantly blunted in Romk−/− mice, consistent with a major salt transport defect in the TAL. In contrast, hydrochlorothiazide produced an exaggerated natriuresis in Romk−/− mice, indicating upregulation of salt absorption by the DCT. Benzamil resulted in a similar increment in absolute Na excretion in both Romk−/− and Romk+/+, indicating no significant upregulation of Na+ transport by ENaC in ROMK null mice. Moreover, hydrochlorothiazide increased the fractional K+ excretion rate in Romk−/− mice, confirming our recent observation that maxi-K channels contribute to distal K+ secretion in the absence of ROMK.

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Section: Discussionmentioning

confidence: 96%

Mouse model of type II Bartter's syndrome. I. Upregulation of thiazide-sensitive Na-Cl cotransport activity

Cantone¹,

Yang²,

Yan³

et al. 2008

American Journal of Physiology-Renal Physiology

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“…31 The diuresis might reflect reduced water reabsorption in the proximal tubule because of inhibition of carbonic anhydrase by furosemide. 32 The renal and hypertensive actions of ACTH excess can be attributed to combined activation of MR and GR, and there is no evidence for alternative pathways for stimulation of ENaC. 33 In addition, MR and GR have reciprocal functionality, because single receptor blockade only blunted the enhanced ENaC activity: the hypertension was similarly reduced by single receptor blockade.…”

Section: Discussionmentioning

confidence: 99%

Mineralocorticoid and Glucocorticoid Receptors Stimulate Epithelial Sodium Channel Activity in a Mouse Model of Cushing Syndrome

2009

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Abstract-Experiments in Cushing patients and healthy control subjects receiving adrenocorticotropic hormone (ACTH) indicate that transient renal sodium retention may contribute to the generation of hypertension. Here we have investigated the effect of chronic ACTH infusion on renal sodium handling in adult male C57BL/6J mice using selective antagonists to dissect mineralocorticoid and glucocorticoid receptor-mediated pathways. Mice were infused via osmotic minipump with ACTH (2.5 g/d) or saline for 2 weeks before being anesthetized for renal function experiments. ACTH caused an increase in blood pressure and a reduction in fractional sodium excretion associated with enhanced activity of the epithelial sodium channel. Given separately, spironolactone and RU38486 blunted the pressor response to ACTH and the increased epithelial sodium channel activity; combined mineralocorticoid and glucocorticoid receptor blockade was required to resolve the response to ACTH excess. Dietary sodium depletion also prevented ACTH-induced hypertension. The effect of increased sodium reabsorption in the distal nephron is offset by downregulation of Na-K-Cl cotransport in the loop of Henle. Sodium excretion is normalized chronically, but blood pressure remains high; acute blockade of V1 receptors and ␣1 adrenoceptors in combination restored blood pressure to control values. In summary, ACTH excess promotes renal sodium reabsorption, contributing to the increased blood pressure; both glucocorticoid and mineralocorticoid receptor pathways are involved. These data are relevant to conditions associated with overactivity of the hypothalamic-pituitary-adrenal axis, such as obesity and chronic stress.

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“…Proton and 23 Na spectra and images were recorded at 200 and 53 MHz, respectively, with a 4.7-T Biospec spectrometer (Bruker, Rheinstetten, Germany) using a homebuilt 3-cm double-tuned surface coil. The rat was placed on the coil in a supine position, keeping the estimated position of the kidney approximately in the middle of the coil (the center of the kidney was 1-1.5 cm above the plain of the coil).…”

Section: In Vivo Mrimentioning

confidence: 99%

“…However, although the kidney is an obvious candidate organ for sodium imaging, sodium MRI was not applied clinically and only a few preclinical studies have thus far been performed (10,18 -22). Most of the previous 23 Na MRI studies that were able to detect the sodium gradient were performed on exposed and therefore stressed kidneys (10,19,21). In addition, Wolff et al measured the sodium signal intensity gradient and the relaxation times in the exposed rabbit kidney at different hydration states (19).…”

Section: Introductionmentioning

confidence: 99%

“…The first, furosemide, is a loop diuretic agent that exerts its influence by blocking the Na ϩ /K ϩ /2Cl Ϫ cotransporter located in the apical membrane of the thick segment of the medullary ascending limb (Ref. (23) and references cited therein). The second, mannitol, is an osmotic diuretic agent that induces a decrease in the resistance of the renal vasculature and an increase in the extracellular fluid volume.…”

Section: Introductionmentioning

confidence: 99%

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Sodium magnetic resonance imaging of diuresis: Spatial and kinetic response

Maril

Margalit

Mispelter

et al. 2005

Magnetic Resonance in Med

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Renal function is highly correlated with the sodium concentration gradient along the corticomedullary axis. The application of 3D high-resolution sodium magnetic resonance imaging (MRI) provided a means to quantify in vivo the spatial and temporal changes in renal tissue sodium concentration under normal and diuretic conditions. A detailed, pixel-by-pixel analysis of the intact rat kidney sodium MR images yielded a quantitative measure of the corticomedullary sodium gradient before and at early and later times after the administration of two distinct diuretic agents, furosemide and mannitol. Furosemide, a loop diuretic, induced a fivefold reduction in the cortical-outer medullary sodium gradient, whereas mannitol, an osmotic diuretic, did not affect this gradient. Both diuretics induced a 50% decrease in the sodium concentration of the inner medulla; however, mannitol exerted its effect twice as fast as furosemide with a 2.5-min exponential decay constant. These specific changes were attributed to the different mechanism of action and site of activity of each diuretic agent. Thus, high-resolution 23 Na MRI offers a unique, noninvasive tool for functional imaging of the kidney physiology. Magn Reson Med 53:545-552, 2005.

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The Site of Action of Furosemide

Cited by 22 publications

References 0 publications

Mouse model of type II Bartter's syndrome. I. Upregulation of thiazide-sensitive Na-Cl cotransport activity

Mouse model of type II Bartter's syndrome. I. Upregulation of thiazide-sensitive Na-Cl cotransport activity

Mineralocorticoid and Glucocorticoid Receptors Stimulate Epithelial Sodium Channel Activity in a Mouse Model of Cushing Syndrome

Sodium magnetic resonance imaging of diuresis: Spatial and kinetic response

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