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

Abstract

Axelsson J, Rippe A, Rippe B. Transient and sustained increases in glomerular permeability following ANP infusion in rats. Am J Physiol Renal Physiol 300: F24 -F30, 2011. First published October 13, 2010 doi:10.1152/ajprenal.00347.2010.-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 Ϫ1 ·min Ϫ1 (Lo-ANP; n ϭ 8) or 800 ng·kg Ϫ1 ·min Ϫ1(Hi-ANP; n ϭ 10)] or 0.9% NaCl (SHAM; n ϭ 16), respectively, and with polydisperse FITC-Ficoll-70/400 (molecular radius 13-90 Å) and 51 Cr-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 () for Ficoll. GFR was also assessed ( 51 Cr-EDTA). In Hi-ANP, there was a rapid (within 5 min), but bimodal, increase in glomerular permeability. to high-molecularweight Ficoll thus reached a maximum at 15 min, after which 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 , 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. capillary permeability; Ficoll; glomerular filtration; glomerular sieving coefficient PLASMA VOLUME OVERLOAD, in conjunction with e.g., congestive heart failure, induces an increased secretion to the circulation of atrial natriuretic peptide (ANP) from the heart upon atrial stretch. By its natriuretic, diuretic, and vasodilating properties, ANP is believed to act physiologically as a compensatory hormone protecting against plasma volume expansion (9, 11, 29). Furthermore, in extrarenal tissues ANP induces a fluid shift from the vascular to the extravascular space, causing increases in hematocrit and plasma protein concentration in nephrecteomized rats (2). Although these effects can be related to vasodilatation, and hence, to increases in capillary surface area and in microvascular pressure, there is now good evidence that ANP directly affects capillary permeability to proteins (11,12,25,29,34) and microvascular hydraulic conductance (16).Microalbuminuria (i.e., moderately elevated albumin excretion rates, ranging from 20 to 200 g/min in humans) is a co...

Acute reactive oxygen species (ROS)-dependent effects of IL-1β, TNF-α, and IL-6 on the glomerular filtration barrier (GFB) in vivo

“…The slight (but significant) GFR changes are in accordance with our previous findings and those by others, showing a slight increase in GFR over time in Sham animals (5,7,9,39). This is probably related to increases in extracellular fluid volume and less blood sampling during the last period of the experiments.…”

“…We have previously studied the glomerular permeability response to different biologically relevant challenges and observed varying patterns of response. For example, the responses to acute anaphylaxis, trauma, angiotensin II, and ANP seem to occur within min (3,4,7,9), whereas the response to e.g., hyperglycemia showed a lag time of ϳ20 min before any permeability increases were observed (5). Furthermore, with respect to the dynamics of permeability changes occurring over time, we have shown that ANP induces a biphasic permeability response, with an early permeability peak at 5 and 15 min and, after 30 min, a more sustained and low-grade increase in for Ficoll 70Å (7).…”

Club cell protein (CC16) in plasma, bronchial brushes, BAL and urine following an inhaled allergen challenge in allergic asthmatics

“…We have previously shown that CC16 is increased in urine following an exercise challenge test (Tufvesson et al 2013). Exercise increases glomerular permeability (Axelsson et al 2011), and we also found that both albumin and protein HC leaked into the urine along with CC16. Mannitol and EVH has also been shown to lead to a minor increase in urinary CC16 levels (Bolger et al 2011b, Kippelen et al 2013), although these challenges should not affect glomerular permeability.…”

A distributed two-pore model: theoretical implications and practical application to the glomerular sieving of Ficoll

“…The GFB is a dynamic barrier in which the permeability can change dramatically even in a short period of time (2)(3)(4)(5). The physiological and pathophysiological mechanisms behind the changes in permeability seem to be mediated primarily by the large-pore system.…”