Furosemide effect on isolated perfused tubules

Burg, M. B.; Stoner, L. C.; Cardinal, Jean; Green, N

doi:10.1152/ajplegacy.1973.225.1.119

Cited by 411 publications

(121 citation statements)

References 25 publications

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“…In the TAL, the paracellular pathway plays an important role in divalent cation reabsorption. Bumetanide, by inhibiting Na ϩ -K ϩ -2Cl Ϫ cotransport, decreases the transepithelial voltage and diminishes cation paracellular reabsorption (5,16). The fact that this loop diuretic decreased Cd 2ϩ transport along LH and DT indicates that in these segments Cd 2ϩ transport may also occur via the paracellular pathway.…”

Section: Discussionmentioning

confidence: 99%

Acute study of interaction among cadmium, calcium, and zinc transport along the rat nephron in vivo

Barbier¹,

Jacquillet²,

Tauc³

et al. 2004

American Journal of Physiology-Renal Physiology

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Barbier, O., G. Jacquillet, M. Tauc, P. Poujeol, and M. Cougnon. Acute study of interaction among cadmium, calcium, and zinc transport along the rat nephron in vivo. Am J Physiol Renal Physiol 287: F1067-F1075, 2004. First published July 27, 2004 doi:10.1152/ajprenal.00120.2004.-This study investigates the effect in rats of acute CdCl2 (5 M) intoxication on renal function and characterizes the transport of Ca 2ϩ , Cd 2ϩ , and Zn 2ϩ in the proximal tubule (PT), loop of Henle (LH), and terminal segments of the nephron (DT) using whole kidney clearance and nephron microinjection techniques. Acute Cd 2ϩ injection resulted in renal losses of Na ϩ , K ϩ , Ca 2ϩ , Mg 2ϩ , PO 4 Ϫ2 , and water, but the glomerular filtration rate remained stable. 45 Ca microinjections showed that Ca 2ϩ permeability in the DT was strongly inhibited by Cd 2ϩ (20 M), Gd 3ϩ (100 M), and La 3ϩ (1 mM), whereas nifedipine (20 M) had no effect. 109 Cd and 65 Zn 2ϩ microinjections showed that each segment of nephron was permeable to these metals. In the PT, 95% of injected amounts of 109 Cd were taken up. 109 Cd fluxes were inhibited by Gd 3ϩ (90 M), Co 2ϩ (100 M), and Fe 2ϩ (100 M) in all nephron segments. Bumetanide (50 M) only inhibited 109 Cd fluxes in LH; Zn 2ϩ (50 and 500 M) inhibited transport of 109 Cd in DT. In conclusion, these results indicate that 1) the renal effects of acute Cd 2ϩ intoxication are suggestive of proximal tubulopathy; 2) Cd 2ϩ inhibits Ca 2ϩ reabsorption possibly through the epithelial Ca 2ϩ channel in the DT, and this blockade could account for the hypercalciuria associated with Cd 2ϩ intoxication; 3) the PT is the major site of Cd 2ϩ reabsorption; 4) the paracellular pathway and DMT1 could be involved in Cd 2ϩ reabsorption along the LH; 5) DMT1 may be one of the major transporters of Cd 2ϩ in the DT; and 6) Zn 2ϩ is taken up along each part of the nephron and its transport in the terminal segments could occur via DMT1. heavy metals; epithelial calcium channel; divalent metal transporter 1; kidney CADMIUM (CD 2ϩ ) IS ONE OF THE most commonly found toxic metals present in our environment. The major sources of exposure to Cd 2ϩ are contaminated food and water, tobacco, and industrial fumes and dusts (16). Cd 2ϩ accumulates in the body, and chronic exposure causes severe nephrotoxicity in humans (16) and animals (2, 4). The renal dysfunction may be due to proximal tubular damage affecting the passive paracellular pathway (14, 27) and decreasing active transcellular ion transport (30). With the use of in vitro models, deleterious effects of Cd 2ϩ have been described on several solute transporters, such as stretch-activated ion channels (24), the epithelial Ca 2ϩ channel (ECaC) transporter (32), the NaPi-II transporter (19), the Na/glucose transporter (1), and the NaSi-1 transporter (25). These acute effects of Cd 2ϩ suggest the involvement of ion transporters in Cd 2ϩ -induced nephropathy. Therefore, the question arises as to whether these transporters are affected in vivo after Cd 2ϩ exposure. To answer this question,...

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Section: Discussionmentioning

confidence: 99%

Acute study of interaction among cadmium, calcium, and zinc transport along the rat nephron in vivo

Barbier¹,

Jacquillet²,

Tauc³

et al. 2004

American Journal of Physiology-Renal Physiology

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“…Na 1 , K 1 , and Cl 2 are cotransported across the apical membrane by NKCC2, an electroneutral Na 1 -K 1 -2Cl 2 cotransporter that is exquisitely sensitive to furosemide, a "loop" diuretic known for 4 decades to inhibit transepithelial Cl 2 transport by the TAL (8). This transporter generally requires the simultaneous presence of all three ions such that the transport of Na 1 and Cl 2 across the epithelium is mutually codependent and dependent on the luminal presence of K 1 (9).…”

Section: Anatomy and Morphologymentioning

confidence: 99%

Thick Ascending Limb of the Loop of Henle

Mount

2014

Clinical Journal of the American Society of Nephrology

141

106

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The thick ascending limb occupies a central anatomic and functional position in human renal physiology, with critical roles in the defense of the extracellular fluid volume, the urinary concentrating mechanism, calcium and magnesium homeostasis, bicarbonate and ammonium homeostasis, and urinary protein composition. The last decade has witnessed tremendous progress in the understanding of the molecular physiology and pathophysiology of this nephron segment. These advances are the subject of this review, with emphasis on particularly recent developments.

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“…Their primary effect is the inhibition of salt and water reabsorption by the renal tubules which then results in increased intratubular osmolality and enhanced urine flow. Advances in the methodology of tubular micropuncture and the discovery of the Burg technique for perfusing isolated tubules (Burg et al, 1973) made it possible to characterize the different mechanisms involved in NaCl reabsorption within the nephron. Using such methods, it is now clear that diuretics are most readily classified according to their maximal capacities to reject filtered sodium chloride.…”

Section: Intrarenal Effectsmentioning

confidence: 99%

Evolution of diuretics and ACE inhibitors, their renal and antihypertensive actions‐parallels and contrasts.

Lant

1987

Brit J Clinical Pharma

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1 The emergence of diuretic drugs and angiotensin converting enzyme (ACE) inhibitors ranks amongst the major therapeutic advances of modern medicine. The discovery of these drug groups arose largely by chance, yet each has dramatically influenced the treatment of congestive cardiac failure and arterial hypertension. 2 The central role which diuretics have had in the management of both oedema and hypertension hinges on their ability to induce a net renal excretion of solute and water by selective interference with either active or passive ion transport processes in different segments of the nephron. Irrespective of sites of action, the continued antihypertensive action of diuretics is characterized by a reduction in plasma volume and extracellular fluid (ECF) volume that lasts for as long as the diuretic is given. The mechanism of this effect remains unclear but may involve autoregulatory reactions that leave cardiac output unaltered but maintain a sustained reduction in total peripheral resistance. 3 ACE inhibitors also lower blood pressure by decreasing total peripheral resistance, leaving cardiac output, plasma volume and ECF volume unchanged. The detailed way these haemodynamic changes are achieved remains unknown but inhibition of converting enzyme present not only in the kidney but also in many extrarenal tissue sites, appears important. In both hypertension and cardiac failure, however, the kidney acts as a key target organ for ACE inhibitors. The increased renal vascular resistance and inappropriate renal salt excretion are reversed with enhanced renal blood flow and saluresis. Both angiotensin II (All) and vasopressin-mediated contraction of glomerular mesangial cells is inhibited, making glomerular filtration more efficient. Reduced aldosterone secondary to blockade of AII formation contributes to saluresis whilst encouraging positive potassium balance. ACE inhibition also impairs breakdown of kinins which may contribute to intrarenal and peripheral vasodilation either on their own or via release of prostaglandins and other vasoactive substances.4 The hypotensive actions of diuretics are potentiated by ACE inhibition primarily through blockade of AII formation and prevention of secondary aldosteronism. In combination, these drugs permit low doses to be used because of their synergistic effects. 5 Caution has to be exercised whenever ACE inhibition is used, without and especially with diuretics, in the management of renovascular hypertension and other low-perfusion states. In these circumstances, AII plays an important autoregulatory role in preserving glomerular filtration through an increase in post-glomerular resistance. Suppression of angiotensin formation with an ACE inhibitor can cause a critical reduction in glomerular perfusion. On the other hand, with careful titration, the dual actions of low-dose loop diuretics and an ACE inhibitor may be highly efficacious in treating severe heart failure and totally prevent such serious metabolic sequelae as azotaemia and hyponatraemia. 6 Unlike the experien...

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Furosemide effect on isolated perfused tubules

Cited by 411 publications

References 25 publications

Acute study of interaction among cadmium, calcium, and zinc transport along the rat nephron in vivo

Acute study of interaction among cadmium, calcium, and zinc transport along the rat nephron in vivo

Thick Ascending Limb of the Loop of Henle

Evolution of diuretics and ACE inhibitors, their renal and antihypertensive actions‐parallels and contrasts.

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