Charge density of renal interstitium

The charge density of renal interstitium was analysed from the volume of distribution of negative native albumin as compared with neutralized albumin, labelled with ¹²⁵I and ¹³¹ I, respectively. The experiments were conducted by infusing the two probes intravenously at a rate which kept the plasma concentrations stable. The concentration in renal hilar lymph, C_lymph(t), will then obey the function C_lymph(t) = C_lymph(t_x) (1-exp—Kt), where C_lymph(t_x) is the steady state Concentration and K the time constant for passage of the tracer through the renal interstitium - the former is dependent on the permeability of the peritubular capillary membrane, whereas the time constant is inversely related to the interstitial distribution volume of the tracers. The lymph-to-plasma concentration ratio (L/P-ratio) of negative, native albumin was found to be lower than that of neutralized albumin, a finding suggesting that the peritubular capillary membrane is negatively charged. Regarding the interstitium, it was calculated from the respective time constants, K, that the interstitium/lymph concentration ratio of negative native albumin was 0.96 ± 0.06 of that of neutralized albumin. This suggests the presence of negative fixed charges repelling negative native albumin. However, since the calculated charge density of — 1.8 ± 1.2 mEq 1^--¹ was not significantly different from zero, it is concluded that the renal interstitium is uncharged. This does not, however, rule out the possibility that, for example, negative groups are fixed to the interstitial matrix, merely that the average fixed charge density of renal interstitial fluid is negligible.     

Renal medullary blood flow studied with the 86-Rb extraction method Methodological considerations

The 86-Rb extraction method was applied for a study of regional renal blood flow. In the cortex, a samling time of 30 s led to an underestimation by about 15% as compared with the microsphere method. This was due to incomplete cortical cellular extraction of rubidium with subsequent rapid wash-out the tracer. In the renal medulla, a sampling of 30–60 s gave valid data with almost complete extraction. A sampling time of only 10 s, i. e. a time similar to the intravascular transit time, gave rise to a 50% underestimation of the inner medullary blood flow. Errors due to transport of rubidium by the tubular fluid were investigated in detail. A theoretical analysis based on equilibrium data revealed a maximal error of about 5%. Studies with micropuncture of distal tubules and studies of the urinary transport showed no or negligible contamination from tubular urine. Under control antidiuretic conditions the blood flow in the cortex was 5.2±0.2 ml-min± g± (mean±SE, n=16), in the outer stripe of the outer zone 2.2±0.1, in the inner stripe 1.5±0.1 and in the inner zone 0.69±0.06.     

The role of antidiuretic hormone in cold-induced diuresis in the anaesthetized rat

The aim of this study was to investigate whether the increased diuresis in consequence of hypothermia is due to a depression of the hypothalamic release of antidiuretic hormone (ADH). The plasma concentration of antidiuretic hormone and the effect of intravenous (i.v.) administration of 65 ng kg^?1 desmopressin (selective V₂-receptor agonist) were determined in the anaesthetized rat. In spite of a 50% (P < 0.001) decrease in glomerular filtration rate, urine flow increased sixfold (P < 0.01) and urine sodium excretion increased sevenfold (P < 0.05), whereas urine osmolality decreased (P < 0.001). At the same time plasma antidiuretic hormone decreased from 7.5 ± 1.1 to 3.8 ± 0.4 pg mL^?1 (P = 0.01). After injection of desmopressin urine flow was completely restored, whereas urine osmolality and sodium excretion were only partially normalized. Since tubular conservation of water and fractional water reabsorption decreased during hypothermia, the diuresis must have resulted from an augmented loss of water. This is further supported by the fact that osmolal excretion was not influenced either by hypothermia or by desmopressin. It is concluded that the diuresis in consequence to hypothermia is due both to a decrease in the release of ADH and to a reduction of renal medullary hypertonicity.     

Renal interstitial volume of the rat kidney

The intravascular plasma volume and the interstitial volume of the rat kidney were determined by an indicator dilution method with a bolus injection of 125-I-labelled human serum albumin and 51-Cr-EDTA into the renal artery and subsequent recording of the indicator-dilution curves in the venous effluent, sampled at intervals of 0.33s. The curves allowed determination of both the mean transit time of the two indicators and total renal plasma flow. The volumes of distribution were obtained by multiplying these two factors. Under control conditions the plasma volume was 93.0±11.2μl/100g rat (mean±SE), which is 17.9% of the total kidney volume. The interstitial volume was 68.3±8.6μl/100g, corresponding to 13.1% of the total kidney volume. During expansion with 0.15 M NaCl, 10% of body weight, the plasma and interstitial volumes were not significantly increased. The values for the two volumes were 101.6±9.7 and 72.8±6.8 μl/100g, respectively. The kidney weight showed, in contrast a clear increase from 539 to 670mg/100g, reflecting the expansion of the proximal and distal tubules due to the increased glomerular filtration rate. It is concluded that although the saline load produced a rise in the renal interstitial pressure, the expected expansion of the interstitium became small, due to the parallel expansion of both the vascular and tubular systems which compress the renal interstitium.     

Hydraulic permeability of the peritubular and glomerular capillary membranes in the rat kidney

The hydraulic conductivity of the peritubular capillary membrane was calculated from I) single nephron fluid reabsorption and 2) net driving force, i. e. from hydrostatic and colloid osmotic pressures in renal interstitium and peritubular capillary blood, as determined by a micropuncture technique and with use of a computer-based model. Under control conditions the net driving force was estimated to be 15.4 mmHg and the hydraulic conductivity 1.04 nl/(mmHg) per 100 g rat. During extracellular volume expansion with 0.15 M saline, 4% and 10% of body weight, the net driving force decreased to 12.5 mmHg and 6.4 mmHg, respectively, whereas the conductivity increased to 1.85 and 3.14 nl/(min-mmHg) per 100 g rat. The reduction in net driving force was compensated by an increased hydraulic conductivity. In the glomeruli the net driving force for filtration increased from 14.2 mmHg under control conditions to 21.2 mmHg and 25.3 mmHg during saline expansion 4% and 10%, whereas the corresponding hydraulic conductivity decreased from 1.13 nl/(min-mmHg) per 100 g rat to 1.03 and 0.80 nl/(min-mmHg) per 100 g rat during the two expansions. During saline expansion the water permeability of the glomerular capillaries is decreased while that of the peritubular capillaries is increased. These changes in the water permeability will lead to retarded excretion of the excess fluid.     

Characteristics of the glomerular capillary membrane of the rat kidney as a hydrated gel. II. On the validity of the model

In our gel model applied to the glomerulus, maintenance of membrane integrity is assumed to be preserved not by rigid elements but by the electro-osmotic and balancing hydrostatic pressure offered by negative, fixed charges such that the membrane is able to withstand the external colloid osmotic and hydrostatic forces. In a previous study we used micropuncture data to estimate the charge densities required to fulfil this assumption. In the present study the validity of the model was examined from the transport of neutral and negative charged myoglobin as derived from their concentrations in renal venous blood. In order to determine the size of the pores, or rather meshes in the network, the venous concentration of [⁵¹Cr]EDTA was also analysed. Based on the ratio between EDTA and neutral myoglobin of 1.08±0.010 (mean±SE, n=9), the equivalent pore radius was calculated to be ～40 Å. The ratio of neutral to negative myoglobin in the two series performed was found to be 0.96±0.018 (n=8) and 0.97±0.05 (n=7), figures which were the same as ratio of 0.97 predicted on theoretical grounds. It is concluded that the experimental data support the hypotheses, although they may also be adapted to the transport in a homogeneously charged membrane; the charge density in this case was estimated at 2.3 mEq L^-1. Assuming that the membrane constitutes a network with quadratic meshes, each fibre would seem to carry binding sites ～80 Å apart and where, in between these binding sites, each fibre was calculated to carry three charges such that the mesh will thus be surrounded by 12 charges.     

Influence of the sympathetic nervous system on renal function during hypothermia

Hypothermia increases preglomerular vasoconstriction leading to decreases in renal blood flow (RBF) and glomerular filtration rate (GFR). Since plasma catecholamine concentrations are increased during hypothermia, the present study was performed to determine the role of the renal sympathetic nervous system in the cold-induced renal vasoconstriction. In Inactin® anaesthetized rats, hypothermia at 28 °C decreased GFR by 50% but failed to alter efferent renal sympathetic nerve activity (ERSNA). Since hypothermia causes shivering which could have influenced the ERSNA recording, Inactin® anaesthetized rats were treated with pethidine or rats were anaesthetized with pentobarbital sodium or Saffan® to eliminate cold-induced shivering. In these non-shivering rats, hypothermia produced a reversible decrease in ERSNA in association with a fall in GFR that was of a similar magnitude as in shivering rats. Further studies in Inactin® anaesthetized rats showed that the fall in GFR was unaltered by renal denervation, bilateral adrenalectomy or intrarenal administration of the α₁-adrenoceptor antagonist prazosin. We conclude that cold-induced renal vasoconstriction is not due to an increase in ERSNA or adrenaline/noradrenaline-mediated activation of renal α₁-adrenoceptors.     

DYNAMICS OF GLOMERULAR ULTRAFILTRATION IN THE NEONATE KIDNEY

Wolgast, M., Elinder, G. and Källskog, Ö. (Department of Physiology and Medical Biophysics, Uppsala University, Uppsala, Sweden, and Department of Paediatrics, Karolinska Institute, St. Göran's Children's Hospital, Stockholm, Sweden). Dynamics of glomerular ultrafiltration in the neonate kidney. Acta Paediatr Scand, Suppl. 305: 66–69, 1983.—In the neonate kidney the glomerular filtration rate is generally depressed both in absolute terms and when calculated per gram kidney weight. Micropuncture studies have revealed that this phenomenon is due, not to changes in the driving pressures or the hydraulic conductivity of the glomerular capillary membrane, but to a retarded glomerular blood flow. A retarded flow will thus mean a steep rise in the protein concentration in parallel to the filtration of the protein-free filtrate. The corresponding steep rise of the colloid osmotic pressure will then induce cessation of the filtration in the distal parts of the glomerular capillary. In dehydrated states this phenomenon will be even more aggravated. An extracellular volume expansion with saline induces relaxation of the two arterioies with subsequent rise in the glomerular blood flow. The rise in the colloid osmotic pressure along the capillary is then less and the filtration can proceed along the whole of the glomerulus. Accordingly the glomerular filtration rate will be increased, reaching figures typical of the mature kidney.     

The cortical and medullary blood flow at different levels of renal nerve activity

The effect of (1) renal denervation and (2) stimulation of the renal nerve on the regional renal blood flow were determined by the Rb uptake method. Under control conditions the total renal blood flow was 3.64±0.09 ml·min^-1·g^-1 tissue increasing significantly (p<0.02) to 4.39±0.28 ml·min^-1·g^-1 after denervation. Upon stimulation of the peripheral portions of the sectioned renal nerves the blood flow decreased almost linearly with the frequency of stimulation reaching 0.99±0.24 ml·min^-1·g^-1 at 10 Hz. Utilizing the relation between blood flow and stimulation frequency the control blood flow correspond to a spontaneous activity of 1.5 Hz. As expected the cortical blood flow responded in the same way as for the total renal blood flow. In the renal medulla denervation gave a much more pronounced response where e.g. the inner medullary flow increased from 0.88±0.09 to 1.30±0.16 ml·min^-1·g^-1, i.e. a 50% increase (p<0.05). Stimulation with 2 Hz produced a steep fall in the blood flow, whereafter it decreased linearly with the stimulation frequency reaching 0.11 ml·min^-1·g^-1 at 10 Hz stimulation. This demonstrates again that the renal medulla is sensitive to renal nerve activity primarily in the low level range. It should be remarked, however, that the 86-Rb uptake method reflects the effective blood flow, which might differ from the blood flow in absolute terms. It is concluded that the renal nerve activity influences the blood flow of all regions of the kidney within the entire range 0–10 Hz. The renal medullary blood flow is affected presumably to a greater extent in the low level range around the basal tone. The sympathetic nerves might then also be important with respect to the urine concentration mechanism.