Sodium Reabsorption by the Henle Loop in Humans

Bartoli, Ettore; Branca, Giovanni; Satta, Andrea; Faedda, Rossana

doi:10.1159/000184370

Cited by 7 publications

(7 citation statements)

References 31 publications

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“…In studies of systemic adminis tration of the drug it has been demonstrated that the hyper tonicity of the interstitium disappears [53,54], water ab straction along the distal tubule and collecting ducts vanish es to nil and, consequently, the urine flow rate approximates the rate of delivery of tubular fluid out of the proximal tu bule [ 16,29,30]. This lends strong support to the theory on which we developed a new clinical-pharmacologic test suit able to measure segmental tubular function in vivo by clear ance measurements alone [1,2], We conclude that F has no proximal effect and that the fractional urine excretion in the presence of inhibiting con centrations o f the agent can be used to closely approximate proximal delivery in clearance studies, without the need of micropuncture.…”

Section: Discussionsupporting

confidence: 56%

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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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Section: Discussionsupporting

confidence: 56%

“…We proposed a technique for measuring segmental tubu lar reabsorption in vivo, which may yield important infor mation on the derangements o f the function of single seg ments of the human nephron in different pathophysiologic conditions [1,2]. This method is based on the pharmacolog ic properties of furosemide (F).…”

Section: Introductionmentioning

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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“…This condition does not allow the evaluation of the validity of the new technique in which we proposed to measure reabsorption by each seg ment of the nephron during water diuresis [21,22], though we can now claim, based on our evidence, that the key assumption of those stud ies was valid.…”

Section: Discussionmentioning

confidence: 84%

“…The issue seems important since we developed a technique to evaluate tu bular function in humans in vivo which is based upon the assumption that furosemide does not act proximally [21,22], Our method has a limit ed application since many authors, according to several studies [23][24][25], believe that furose mide does inhibit proximal reabsorption. How ever, there are other studies indicating that furo semide acts exclusively along the thick ascend ing limb of Henle's loop [26,27].…”

Section: Discussionmentioning

confidence: 99%

“…A similar correlation was present by plotting the delivery out of the ED tubule (r = 0.77, p <0.0001), since ED and LP deliveries were significantly correlated each with the other (r = 0.61, p < 0 .0 1 ). The use of urine flow rate during furosemide to estimate proximal reabsorption was another assumption on which our technique [21,22] was based.…”

Section: Discussionmentioning

confidence: 99%

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Micropuncture Study of the Effect of Furosemide on Proximal and Distal Tubules of the Rat Nephron

Romano

Favret²,

Bartoli³

1995

Kidney Blood Press Res

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The tubular effects of furosemide were studied by micropuncture and clearance techniques on 20 rats. Collections of tubular fluid (TF) from early distal (ED) and late proximal (LP) segments of the same nephrons and of different nephrons were performed during baseline conditions. Re-collections were taken from the same sites and new collections from different nephrons after 10 mg/kg furosemide. The glomerular filtration rate (GFR) was 1,309 ± 212µl/min during baseline, and 1,348 ± 199 µl/min after furosemide (p > 0.89); while the urine flow rate rose from 36 ± 8 to 167 ± 30µl/min (p < 0.001). The nephron filtration rate (NFR) was not different in 46 paired distal (33.3 ± 2.6 nl/min) versus proximal samples (34.2 ± 2.9 nl/min, p > 0.72), neither was it different during baseline (37.2 ± 1.4, n = 120) as compared to furosemide (37.2 ± 2.7, n = 91, p > 0.99). The percent reabsorption (PR) at the ED sampling site was 87 ± 4% during baseline, and 89 ± 3% in 13 paired samples during furosemide (p > 0.47). PR at the LP sampling sites was 83 ± 2% during baseline, and 80 ± 2% in 26 paired samples during furosemide (p > 0.63). In 31 paired ED-LP collections, PR was 82+4 (ED) versus 72 ± 4% (LP) during baseline, and 87 ± 3 versus 74 ± 6%, respectively, during furosemide. The respective collection rates were 4.6 ± 1.0 versus 9.5 ± 1.3 nl/min during baseline (p < 0.0001), 5.8 ± 2.3 versus 8.7 ± 3.0 nl/min during furosemide. The LP-ED differences obtained during baseline were not different from those measured during furosemide for the collection rate, PR and NFRs. The absolute LP resorption rate was not significantly different during baseline as compared to furosemide. Thus, furosemide did not affect the difference between ED and LP collection sites in collection rate, absolute and fractional reabsorption, in the absence of changes in GFR and NFR. These data indicate that furosemide acts solely along Henle’s loop, where it blocks Na⁺ transport. The urine flow rate rises during furosemide because water abstraction along the distal tubule is reduced by the isotonicity of ED TF, and along the collecting ducts by the isotonicity of the medullary and papillary interstitium caused by the diuretic. We conclude that under the conditions of the present study, furosemide has no proximal effect.

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Consistency of nephron filtration measurements by collection of total tubular fluid from different proximal sites

Romano

D’Amato

Favret

et al. 1997

European Journal of Applied Physiology

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The stability of single nephron glomerular filtration rate (SNGFR) is assured by specific mechanisms such as the tubulo-glomerular feedback system and autoregulation. Studies on renal physiology rely heavily on the measurements of SNGFR, which are feasible only in animals. The measurement of SNGFR by collection of total tubular fluid may be influenced by the fall in intratubular hydrostatic pressure that may reflect the negative pressure applied to the sampling pipette. This effect may become more important with shortening of the distance between the sampling site and the Bowman space. We analysed this putative effect by performing collections of total tubular fluid from the late proximal (LP), and then from the early proximal (EP) segment of the same nephrons. In 128 paired collections LP-SNGFR averaged 35 (SEM 2) nl x min(-1), and was no different from the paired mean EP-SNGFR of 37 (SEM 2) nl x min(-1), P > 0.179. Then EP- and LP- SNGFR were significantly correlated (r = 0.77, P < 0.001). As expected, the respective paired means of absolute and percentage reabsorptions, and those of collection rates were significantly different. The average SNGFR computed from each LP and EP paired measurement was significantly correlated with the simultaneously measured kidney glomerular filtration rate, GFR (r = 0.60, P < 0.0001). The ratio of GFR to SNGFR indicated the expected number of glomeruli. These data would indicate that the sampling site does not influence the measurement of SNGFR in the proximal tubule when the total fluid collection technique is correctly performed. They also exclude a time-dependent activation of the macula densa capable of upregulating SNGFR within the interval elapsing between the beginning of LP and the completion of EP collections, which in our study averaged 4.4 (SEM 0.1) min.

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Sodium Reabsorption by the Henle Loop in Humans

Cited by 7 publications

References 31 publications

Microinjection Studies on the Effect of Furosemide on the Rat Nephron

Microinjection Studies on the Effect of Furosemide on the Rat Nephron

Micropuncture Study of the Effect of Furosemide on Proximal and Distal Tubules of the Rat Nephron

Consistency of nephron filtration measurements by collection of total tubular fluid from different proximal sites

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