Transient and sustained increases in glomerular permeability following ANP infusion in rats

The present study was performed to investigate the effects of systemic atrial natriuretic peptide (ANP) infusion on the glomerular permeability to macromolecules in rats. In anesthetized Wistar rats (250–280 g), the left urether was cannulated for urine collection while simultaneously blood access was achieved. Rats were continuously infused intravenously with ANP [30 ng·kg−1·min−1 (Lo-ANP; n = 8) or 800 ng·kg−1·min−1 (Hi-ANP; n = 10)] or 0.9% NaCl (SHAM; n = 16), respectively, and with polydisperse FITC-Ficoll-70/400 (molecular radius 13–90 Å) and 51Cr-EDTA for 2 h. Plasma and urine samples were taken at 5, 15, 30, 60, and 120 min of ANP infusion and analyzed by high-performance size-exclusion chromatography (HPLC) for determination of glomerular sieving coefficients (θ) for Ficoll. GFR was also assessed (51Cr-EDTA). In Hi-ANP, there was a rapid (within 5 min), but bimodal, increase in glomerular permeability. θ to high-molecular-weight Ficoll thus reached a maximum at 15 min, after which θ returned to near control at 30 min, to again increase moderately at 60 and 120 min. In Lo-ANP, there was also a rapid, reversible increase in glomerular θ, returning to near control at 30 min, followed by just a tendency of a sustained increase in permeability, but with a significant increase in “large-pore” radius. In conclusion, in Hi-ANP there was a rapid increase in glomerular permeability, with an early, partly reversible permeability peak, followed by a (moderate) sustained increase in permeability. In Lo-ANP animals, only the initial permeability peak was evident. In both Lo-ANP and Hi-ANP, the glomerular sieving pattern observed was found to mainly reflect an increase in the number and radius of large pores in the glomerular filter.

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Effects of early endotoxemia and dextran-induced anaphylaxis on the size selectivity of the glomerular filtration barrier in rats

AJP Renal Physiology ◽

10.1152/ajprenal.90263.2008 ◽

2009 ◽

Vol 296 (2) ◽

pp. F242-F248 ◽

Cited By ~ 24

Author(s):

Josefin Axelsson ◽

Anna Rippe ◽

Daniele Venturoli ◽

Per Swärd ◽

Bengt Rippe

Keyword(s):

Fluorescein Isothiocyanate ◽

Size Exclusion ◽

Glomerular Permeability ◽

Left Ureter ◽

Filtration Barrier ◽

Dextran 70 ◽

Exclusion Chromatography ◽

Plasma And Urine Samples ◽

Permeability Alterations ◽

Molecular Radius

This study was performed to investigate the glomerular permeability alterations responsible for the microalbuminuria occurring in endotoxemia and during anaphylactic shock. In anesthetized Wistar rats, the left ureter was catheterized for urine collection while, simultaneously, blood access was achieved. Endotoxemia was induced by lipopolysaccharide (LPS) from Escherichia coli, and glomerular permeability was assessed at 60 and 90 ( n = 7) and 120 ( n = 7) min. Anaphylaxis was induced by a bolus dose of Dextran-70, and glomerular permeability assessed at 5 min ( n = 8) and 40 min ( n = 9). Sham animals were followed for either 5 or 120 min. The glomerular sieving coefficients (θ) to fluorescein isothiocyanate-Ficoll (70/400) were determined from plasma and urine samples and assessed using size-exclusion chromatography (HPLC). After start of the LPS infusion (2 h), but not at 60 or 90 min, θ for Ficoll70Å had increased markedly [from 2.91 × 10−5 ± 6.33 × 10−6 to 7.78 × 10−5 ± 6.21 × 10−6 ( P < 0.001)]. In anaphylaxis, there was a large increase in θ for Ficolls >60 Å in molecular radius already at 5 min, but the glomerular permeability was completely restored at 40 min. In conclusion, there was a transient, immediate increment of glomerular permeability in dextran-induced anaphylaxis, which was completely reversible within 40 min. By contrast, endotoxemia caused an increase in glomerular permeability that was manifest first after 2 h. In both cases, θ to large Ficoll molecules were markedly increased, reflecting an increase in the number of large pores in the glomerular filter.

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Rapid, dynamic changes in glomerular permeability to macromolecules during systemic angiotensin II (ANG II) infusion in rats

AJP Renal Physiology ◽

10.1152/ajprenal.00153.2012 ◽

2012 ◽

Vol 303 (6) ◽

pp. F790-F799 ◽

Cited By ~ 30

Author(s):

Josefin Axelsson ◽

Anna Rippe ◽

Carl M. Öberg ◽

Bengt Rippe

Keyword(s):

Angiotensin Ii ◽

High Performance ◽

Size Exclusion ◽

Ang Ii ◽

Glomerular Permeability ◽

Small Pore ◽

Exclusion Chromatography ◽

Plasma And Urine Samples ◽

Log Normal

The actions of systemic angiotensin II (ANG II) infusions on glomerular permeability were investigated in vivo. In anesthetized Wistar rats (250–280 g), the left ureter was cannulated for urine collection, while simultaneously blood access was achieved. Rats were continuously infused intravenously with either of four doses of ANG II ranging from 16 ng·kg−1·min−1 (Lo-ANG II) to 1.82 μg·kg−1·min−1 (Hi-ANG II), and in separate experiments with aldosterone (Aldo; 0.22 mg·kg−1·min−1), or with the calcium channel blocker nimodipine, or with the Aldo antagonist spironolactone together with a high ANG II dose (910 ng·kg−1·min−1; Hi-Int-ANG II), respectively, and with polydisperse FITC-Ficoll-70/400 (molecular radius 10–80 Å) and 51Cr-EDTA. Plasma and urine samples were taken at 5, 15, 30, 60, and 120 min and analyzed by high performance size-exclusion chromatography for determination of glomerular sieving coefficients (θ) to Ficoll. Mean arterial pressure (MAP) and glomerular filtration rate (GFR) were also assessed. For ANG II, there was a rapid, marked, partly reversible increase in glomerular permeability (θ) for Ficoll molecules >34 Å in radius, peaking at 5–15 min, which was completely abrogated by the ANG II blocker candesartan but not affected by spironolactone at 15 and 30 min. For Aldo, the response was similar to that found for the lowest dose of ANG II infused. For the two highest ANG II doses given (Hi-Int-ANG II and Hi-ANG II), GFR decreased transiently, concomitant with marked, sustained increases in MAP. Nimodipine completely blocked all hemodynamic ANG II actions, whereas the glomerular permeability response remained unchanged. Thus ANG II directly increased glomerular permeability independently of its hemodynamic actions and largely independently of the concomitant Aldo response. The ANG II-induced increases in glomerular permeability were, according to a two-pore and a log-normal distributed pore model, compatible with an increased number of “large pores” in the glomerular filter, and, to some extent, an increase in the dispersity of the small-pore radius.

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