Oxytocin and renal function in the rat; an investigation of a possible proximal site of action

1983 ◽  
Vol 102 (4) ◽  
pp. 517-520 ◽  
Author(s):  
H. O. Garland ◽  
R. J. Balment ◽  
M. J. Brimble

Abstract. Direct measurements of proximal tubular fluid reabsorption have been employed to examine the possible renal site of action of oxytocin. In whole kidney studies the natriuresis and chloriuresis, which occurred during the period of oxytocin infusion, did not coincide with the associated diuresis. The latter reached a peak 10–20 min after hormone administration has ceased. The separation in the saliuretic and diuretic responses underlines the apparent independence of these actions of oxytocin on the renal handling of water and electrolytes. The disturbances in renal function were not related to any change in glomerular filtration rate (gfr) and an examination of single nephron function failed to detect any significant effect of oxytocin on proximal tubular reabsorption. The renal actions of oxytocin would therefore appear to emanate from altered tubular rather than glomerular function, though the present study provides no support for a proximal site of action.

1985 ◽  
Vol 107 (1) ◽  
pp. 127-131 ◽  
Author(s):  
J. Walker ◽  
H. O. Garland

ABSTRACT Whole kidney and renal micropuncture techniques were used to investigate the effects of chronic prolactin treatment on kidney function in anaesthetized female rats. At the whole kidney level, glomerular filtration rate (GFR) and fluid reabsorption were both significantly (P<0·02) increased in the hormone-treated group. At the single nephron level, GFR and proximal fluid reabsorption were also increased (P<0·05) by prolactin treatment. Fractional reabsorption was also enhanced at the proximal tubular level in hormone-treated animals. Such changes in renal function are similar to those seen in rat pregnancy and cervically stimulated pseudopregnancy. Since circulating prolactin concentrations are increased in both reproductive states, the hormone may play an important role in establishing the characteristic renal changes seen therein. J. Endocr. (1985) 107, 127–131


F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 83 ◽  
Author(s):  
Jurgen Schnermann ◽  
Mona Oppermann ◽  
Yuning Huang

An increase of glomerular filtration rate (hyperfiltration) is an early functional change associated with type I or type II diabetes mellitus in patients and animal models. The causes underlying glomerular hyperfiltration are not entirely clear. There is evidence from studies in the streptozotocin model of diabetes in rats that an increase of proximal tubular reabsorption results in the withdrawal of a vasoconstrictor input exerted by the tubuloglomerular feedback (TGF) mechanism. In the present study, we have used micropuncture to assess single nephron function in wild type (WT) mice and in two strains of type I diabetic Ins2+/- mice in either a C57Bl/6 (Akita) or an A1AR-/- background (Akita/A1AR-/-) in which TGF is non-functional. Kidney glomerular filtration rate (GFR) of anesthetized mice was increased by 25% in Akita mice and by 52% in Akita/A1AR-/-, but did not differ between genotypes when corrected for kidney weight. Single nephron GFR (SNGFR) measured by end-proximal fluid collections averaged 11.8 ± 1 nl/min (n=17), 13.05 ± 1.1 nl/min (n=23; p=0.27), and 15.4 ± 0.84 nl/min (n=26; p=0.009 compared to WT; p=0.09 compared to Akita) in WT, Akita, and Akita/A1AR-/- mice respectively. Proximal tubular fluid reabsorption was not different between WT and diabetic mice and correlated with SNGFR in all genotypes. We conclude that glomerular hyperfiltration is a primary event in the Akita model of type I diabetes, perhaps driven by an increased filtering surface area, and that it is ameliorated by TGF to the extent that this regulatory system is functional.


1985 ◽  
Vol 248 (3) ◽  
pp. F319-F331
Author(s):  
C. B. Wilson ◽  
R. C. Blantz

Immunologic models of renal injury are useful in the study of pathophysiology. Some of these models have already been used in glomerular micropuncture studies and were shown to be approachable with the same techniques that were developed to study normal renal function. The typical decrease in the glomerular permeability coefficient found in such studies is countered by an increase in the hydrostatic pressure gradient, minimizing decreases in single nephron filtration rate. Antibody mechanisms involving either direct glomerular (and tubular) fixation of antibody or accumulation of immune complex materials provide an array of acute and chronic lesions for evaluation with relevance to the bulk of immune glomerular and tubular lesions in humans. The influences of varied and overlapping immune mediator systems are also useful areas for physiologic assessment. The tools of the renal immunopathologist may be useful to the physiologist in identifying and localizing the effects of transport systems central to renal function. The collaborative interaction of investigators skilled in immunology, pathology, and physiology is necessary to achieve optimum scientific value.


1975 ◽  
Vol 229 (3) ◽  
pp. 813-819 ◽  
Author(s):  
A Grandchamp ◽  
Scherrer ◽  
D Scholer ◽  
J Bornand

The effect of small changes in intraluminal hydrostatic pressure (P) on the tubular radius (r) and the net fluid reabsorption per unit of surface area of the tubular wall (Js) has been studied in the proximal tubule of the rat kidney. The split-drop method was used to simultaneously determine Js and r. Two standardized split-drop techniques A and B allow selective change in P. P was 31.6 +/- 1.3 mmHg in technique A and 15.5 +/- 1.5 in technique B. The pressure difference significantly affected the tubular radius; r was 21.9 +/- 0.4 and 18.6 +/- 0.5 mum in the split drop A and B, respectively. In contrast, net transepithelial fluid reabsorption Js was unchanged. Js amounted to 2.72 +/- 0.20, and 2.78 +/- 0.33 10(-5) cm3 cm-2 s-1 in split drop A and B. The absence of variations in Js could result from two opposite effects of pressure. P might enhance Js by increased ultrafiltration. However, the rise in r might decrease the density of the intraepithelial transport paths per unit area of tubular wall and therefore might decrease Js.


1983 ◽  
Vol 245 (2) ◽  
pp. F247-F253 ◽  
Author(s):  
J. C. Pelayo ◽  
R. D. Fildes ◽  
G. M. Eisner ◽  
P. A. Jose

The renal responses to a specific dopamine antagonist (cis-flupentixol) and its stereoisomer (trans-flupentixol), a weak dopamine antagonist, were examined during hydropenia and Ringer loading in anesthetized rats. During hydropenia glomerular filtration (GFR), absolute (UNaV), and fractional (FENa) sodium excretion rates were similar as were single-nephron filtration (SNGFR) and proximal tubular flow rate (VTF). After Ringer loading GFR, UNaV, and FENa increased in all groups, but the increments were less in the cis-flupentixol than in the control or trans-flupentixol group. SNGFR and VTF increased similarly in all groups. In another series of experiments Ringer loading was performed prior to drug administration. Perfusion pressure (PP) was decreased in trans-flupentixol rats by aortic constriction to control for cis-flupentixol-induced reduction in PP. UNAV and FENa were lower in the cis-flupentixol- than trans-flupentixol-treated rats at comparable PP and GFR. In conclusion, dopamine blockade attenuated the natriuresis of Ringer loading; the mechanism is uncertain but may be related to a tubular effect at a site beyond the proximal convoluted tubule and/or in deeper nephrons.


1947 ◽  
Vol 86 (4) ◽  
pp. 339-356 ◽  
Author(s):  
H. E. Harrison ◽  
H. Bunting ◽  
N. K. Ordway ◽  
W. S. Albrink

Severe and persistent impairment of kidney function has been produced in dogs by intravascular hemolysis due to arsine, or by the intravenous injection of solutions of dog hemoglobin and methemoglobin. The kidneys of these animals have been examined by the usual histological methods and also by means of the ferrocyanide histochemical method to determine the pathogenesis of the renal injury. These observations indicate that obstruction to flow of urine through the renal tubules is an important factor in the early reduction of kidney function. The material filling the lumina of the renal tubules was found to be chiefly methemoglobin in concentrated solution of gel-like consistency. No evidence of formation of a pigment insoluble at the pH of the urine such as hemochromogen or hematin was found. The cessation of urine flow is most readily explained by the increased viscosity of the tubule contents. The intravenous administration of methemoglobin was found to produce more severe renal injury than the injection of equal amounts of oxyhemoglobin. Necrosis of the proximal convoluted tubule cells was present as a late lesion in animals injected with methemoglobin, large amounts of hemoglobin, or following extensive intravascular hemolysis. Such injury is probably a contributing factor in the persistent severe depression of renal function seen in these animals. Following disappearance of most of the intratubular pigment, a large number of collapsed tubules lined by hemosiderin-filled cells were found. The ferrocyanide histochemical studies indicated that these represented non-functioning nephrons although no obstructing intratubular material was present. Direct measurements in two animals failed to reveal any reduction of renal blood flow following the injection of methemoglobin in amounts sufficient to produce renal injury.


1979 ◽  
Vol 237 (1) ◽  
pp. F63-F74 ◽  
Author(s):  
L. C. Moore ◽  
J. Schnermann ◽  
S. Yarimizu

Tubuloglomerular feedback (TGF) mediation of autoregulation was investigated by measuring the response of single nephron glomerular filtration rate (SNGFR) to changes in arterial pressure (AP) following acute or chronic TGF inhibition. In hydropenic rats with intact TGF, distal SNGFR was 25.0 +/- 1.2 (SE) and 23.9 +/- 1.4 nl/min at AP of 111 and 135 mmHg, respectively. In the same 20 nephrons during proximal tubular microinfusion of furosemide, distal SNGFR was 23.6 +/- 1.4 (n = 16) and 29.7 +/- 1.4 nl/min (n = 20) (P less than 0.001, n = 16) at 112 and 133 mmHg. When determined proximally, SNGFR was 25.6 +/- 1.0 and 29.5 +/- 0.9 nl/min (P less than 0.001, n = 31) at 112 and 157 mmHg; kidney GFR increased similarly. These data and the predictions of a GFR model were then used to estimate autoregulatory efficiency. This analysis indicated that partial autoregulation occurred during TGF inhibition. Therefore, TGF is an essential, but probably not the only, mechanism mediating SNGFR autoregulation.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S64-S64
Author(s):  
Anthony Mills ◽  
Kimberly Workowski ◽  
Thomas Campbell ◽  
Paul Benson ◽  
Gordon Crofoot ◽  
...  

Abstract Background In the DISCOVER PrEP trial, emtricitabine/tenofovir alafenamide (F/TAF) was noninferior to emtricitabine/tenofovir disoproxil fumarate (F/TDF) for HIV prevention. Here, we report on the renal outcomes of F/TAF and F/TDF among all DISCOVER participants and in those on baseline F/TDF PrEP who were randomized to F/TAF. Methods In total, 5387 men who have sex with men (MSM) and transgender women (TGW) at risk for HIV were randomized 1:1 to receive blinded F/TDF or F/TAF taken once daily (full cohort). Of these, 905 were on F/TDF PrEP at enrollment; of whom, 465 were randomized to F/TAF. Renal function and safety assessments included urinalysis (UA), estimated glomerular filtration rate (eGFRCG), urine protein:creatinine (Cr) ratio (UPCR), markers of proximal tubular function (β2-microglobulin:Cr ratio [β2M:Cr] and retinol-binding protein:Cr ratio [RBP:Cr]) and investigator-reported renal adverse events (AEs). Week 48 data are presented. Results In the full cohort, F/TAF was associated with more favorable changes in eGFRCG, β2M:Cr, and RBP:Cr compared with F/TDF (Table 1). Treatment-emergent proteinuria by UA was more common with F/TDF than F/TAF (24.3% vs. 21.3% P = 0.009), as were treatment-emergent elevations in UPCR >200 mg/g (35 [1.5%] vs. 16 [0.7%], P = 0.005). Compared with F/TDF, participants taking F/TAF had numerically fewer study drug-related renal AEs, severe study drug-related renal AEs, and discontinuations due to renal AEs (Table 2). Proximal renal tubulopathy (Fanconi syndrome) was reported in one participant in the F/TDF arm and none in the F/TAF arm. In participants on F/TDF PrEP at enrollment who were randomized to F/TAF, statistically significant increases in eGFRCG were apparent as early as week 4 (Table 1 and Figure 1), as were decreases in tubular proteinuria (Table 1). Renal biomarker changes in PrEP-naïve participants mirrored those in the full cohort. Conclusion Through 48 weeks, MSM and TGW taking F/TAF for PrEP had significantly better measures of renal function and fewer study-drug-related renal AEs compared with those taking F/TDF; switching from F/TDF to F/TAF was associated with improvements in eGFRCG and tubular function biomarkers. F/TAF for PrEP is effective and has a superior renal safety profile compared with F/TDF. Disclosures All Authors: No reported Disclosures.


2011 ◽  
Vol 55 (4) ◽  
pp. 249-255 ◽  
Author(s):  
Fábio M. Montenegro ◽  
Lenine G. Brandão ◽  
Gustavo F. Ferreira ◽  
Delmar M. Lourenço Jr. ◽  
Regina M. Martin ◽  
...  

OBJECTIVE: Little information is available on glomerular function changes after surgical treatment of primary hyperparathyroidism. The acute effects of some head and neck operations on renal function were studied. MATERIAL AND MATHODS: Retrospective analysis of changes in creatinine levels and estimated glomerular filtration rate (eGFR) after surgery. Preoperative values were compared with values available until 72 hours after the operation. RESULTS: In tertiary hyperparathyroidism, mean preoperative and postoperative eGFR values were 57.7 mL/min and 40.8 mL/min (p < 0.0001), respectively. A similar decrease was observed after parathyroidectomy for primary hyperparathyroidism, from 85.4 mL/min to 64.3 mL/min (p < 0.0001). After major head and neck procedures, there was a slight increase in eGFR (from 94.3 mL/min to 105.4 mL/min, p = 0.002). CONCLUSION: Parathyroidectomy may be followed by a transient decrease in eGFR that is not often observed in other head and neck operations.


1981 ◽  
Vol 241 (3) ◽  
pp. F238-F243
Author(s):  
D. A. Hartupee ◽  
A. H. Gillies ◽  
F. G. Knox

Previous studies concerning the measurement of single nephron filtration rate have shown that collections of proximal tubular fluid, in which an oil drop is held in a constant position, do not affect intratubular pressure in the early proximal tubule in the hydropenic rat. Since intratubular pressures are higher in the dog than the rat, we investigated the effect of position-controlled collections on proximal pressure and single nephron filtration rate (SNGFR) in the dog. During position-controlled collections, early proximal pressure fell 5.8 +/- 0.9 mmHg and SNGFR was 76.3 +/- 5.3 nl/min. During proximal re-collections, in which proximal pressure was maintained near the free-flow value using a long immobile oil block, SNGFR was significantly less, 44.4 +/- 5.5 nl/min. For each micropunctured kidney, SNGFR was also estimated by dividing GFR by the number of glomeruli (mean, 5.4 +/- 0.5 X 10(5)). Estimated SNGFR (50.9 +/- 6.3 nl/min) was not significantly different from pressure-controlled SNGFR but was significantly less than position-controlled SNGFR. Accordingly, in the dog, early proximal pressure decreases during position-controlled collection of proximal tubular fluid, resulting in an overestimation of SNGFR. This artifact can be avoided by controlling the intratubular pressure during collection of tubular fluid.


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