Kinetics of the glomerular ultrafiltration in the rat kidney. A theoretical study.

The glomerular filtration process was evaluated theoretically from micropuncture data obtained from Sprague-Dawley rats. The hydrostatic pressures in the glomerular capillaries and Bowman's space minus the oncotic pressure in systemic plasma gave the net driving force at the proximal end of the glomerular capillary. From the single nephron filtration fraction the mean net driving force over the glomerular membrane was calculated to be 20 mm Hg during normotension, decreasing to 12 mm Hg during a perfusion pressure of 80 mm Hg. The hydraulic permeability for one glomerulus was 0.7-0.8 nl/min-100 g b.wt. mmHg. The pressures at the distal end of the glomerular capillaries were 13 and 6 mm Hg under the above two conditions, indicating non-equilibrium of the filtration process at the end of the glomerular capillary. It was shown that the glomerular filtration rate is mainly influenced by the driving pressures. During hypotension an increased plasma flow dependency was evident. Brenner et al. found a filtration equilibrium and a plasma flow dependent glomerular filtration rate in a mutant Wistar rat strain. The discrepancy between their results and ours is due to the low glomerular plasma flow and hydrostatic pressures in the Wistar rats. It is concluded from our results that both pre- and postglomerular resistances may influence the glomerular filtration rate and glomerular plasma flow independently.     

Modulation of proximal tubular hydraulic conductivity by peritubular capillary oncotic pressure

Fluid absorption from the proximal tubular lumen is probably a multifactorial process. Earlier studies from our laboratory have indicated that a transepithelial hydrostatic and oncotic pressure difference may be the driving force for as much as 30% of the reabsorbed fluid. During saline volume expansion proximal tubular reabsorption declines and the present experiments were undertaken to investigate whether this reduction could be caused by changes in the passively driven flux component. The hydraulic conductivity was therefore determined from the reabsorptive rate in split oil droplets with normal and high hydrostatic pressure gradients across the wall, at the same time as the peritubular capillary net-work was perfused with solutions containing a colloid of high or low concentration. In the reabsorption experiments the split oil droplet radius was measured and in a separate series of experiments the relationship between droplet radius and pressure was determined; this was found to be 7.3 mmHg pressure increase per 1 μm increase in radius. The increase in the rate of reabsorption from the droplets due to increased intraluminal hydrostatic pressure was 1.02±0.13 nl/min/mm tubular length when a solution with a high colloid concentration was perfused through the capillary net-work, compared with 0.41=0.11 nl/min/mm tubular length when a low colloid containing solution was used for perfusion. The hydraulic conductance in the proximal tubular wall at high colloid perfusion was calculated to be 0.54 nl/min mm mmHg while at a low capillary colloid oncotic pressure it was significantly lower 0.025 nl/min mm mmHg. This drop in hydraulic conductance might be one factor responsible for the decline in fluid absorption in animals exposed to saline volume expansion.     

Kinetics of the Glomerular Ultrafiltration in the Rat Kidney. A Theoretical Study

The glomerular filtration process was evaluated theoretically from micropuncture data obtained from Sprague-Dawley rats. The hydrostatic pressures in the glomerular capillaries and Bowman's space minus the oncotic pressure in systemic plasma gave the net driving force at the proximal end of the glomerular capillary. From the single nephron filtration fraction the mean net driving force over the glomerular membrane was calculated to be 20 mm Hg during normotension, decreasing to 12 mm Hg during a perfusion pressure of 80 mm Hg. The hydraulic permeability for one glomerulus was 0.7-0.8 nl/min. 100g b. wt. mmHg. The pressures at the distal end of the glomerular capillaries were 13 and 6 mm Hg under the above two conditions, indicating non-equilibrium of the filtration process at the end of the glomerular capillary. It was shown that the glomerular filtration rate is mainly influenced by the driving pressures. During hypotension an increased plasma flow dependency was evident. Brenner et al. found a filtration equilibrium and a plasma flow dependent glomerular filtration rate in a mutant Wistar rat strain. The discrepancy between their results and ours is due to the low glomerular plasma flow and hydrostatic pressures in the Wistar rats. It is concluded from our results that both pre- and postglomerular resistances may influence the glomerular filtration rate and glomerular plasma flow independently.     

Determinants of peritubular capillary fluid uptake in hydropenia and saline and plasma expansion.

Hydrostatic (HPc) and oncotic (phic) pressures within the peritubular capillary, tubular pressure (Pt), nephron filtration rate, and plasma flow, and proximal fractional and absolute reabsorption (APR) were measured in anesthetized rats during hydropenia and plasma and saline expansion. Net interstitial pressure (phii-HPi) was estimated from subcapsular hydrostatic and oncotic pressures during saline expansion and these data were applied to a mathematical model of peritubular capillary fluid uptake to determine the profile of effective reabsorption pressure (ERP) with distance (x*) alongthe capillary and calculate the peritubular capillary permeability coefficient (LpAr). ERPX* = (PHIC MINUS HPC)X* MINUS (PHII MINUS HPi) and APR = ERPX*LpAr.During saline expansion phii minus HPi was -12.1 plus or minus 0.8 mmHg and ERP,3.8 mm. The LpAr was 0.07 nl/s per g KW per mmHg, and this value was applied to hypropenia and plasma expansion to determine ERP and phii minus HPi. The phiiminus HPi was +6.0 and +5.0 mmHg, respectively, and ERP was 4.1 and 3.5 mmHg.Efective reabsorptive pressure remained positive along x* in all states, and phii minus HPi correlated best changes in phic and poorly with changes in efferent plasma flow. The APR did not correlate with either calculated phii minus HPi or the transepithelial driving pressure, Pt + phii minus HPi.     

Permeability of renal capillaries. III. Theoretical analysis of hydraulic conductivity, pore structure and electric properties

The functional characteristics of the capillary membranes of rat kidneys were analysed in a computer-based model utilizing previous data on the hydraulic conductivity of the membranes and transport by diffusion, hydraulic flow and ion migration of: inulin, myoglobin (negative, neutral and positive), horseradish peroxidase (negative and neutral), lactate dehydrogenase (negative, neutral and positive) and albumin. The results showed that in the peritubular capillaries the main fluid reabsorption (26.8 x 10(-8) ml nephron-1 100 g body wt-1) occurs through a set of 20 A pores with a total pore area over pore length of 30 cm x (nephron 100 g body wt)-1, whereas the plasma proteins enter the renal interstitium through a few 140 A large pores with a total pore area over pore length of 7.2 x 10(-4) cm and a fluid reabsorption of 1.2 x 10(-10) ml nephron-1 100 g body wt-1. The intramembranous concentration of negative fixed charges in the large pore system was estimated at 20 mM (range 15-22 mM). Since this was accompanied by a potential difference of 0.3 mV, a net driving electro-osmotic force, favouring reabsorption, of 4 mmHg developed. The charges and the electro-osmotic force was found to be essential for protein transport, since if the membrane was uncharged, the transport and interstitial concentration of e.g. albumin was twice as high. The glomerular capillaries seem to have a more homogeneous structure, that is in essence a one-pore system; the pore radius was 44 A, the total pore area over pore length 2.8 cm and the concentration of negative fixed charges 40 mM (range 37-43 mM).     

Variation of proximal tubular reabsorptive capacity by volume expansion and aortic constriction during constancy of peritubular capillary protein concentration in rat kidney

Summary The present study was undertaken in anesthetized rats to examine the effect of aortic constriction and volume expansion on proximal tubular sodium reabsorption during constancy of flow and fluid composition in the peritubular circulation of the kidney. Efferent arterioles and branch capillaries were perfused at 625 nl/min with an artificial perfusate containing 9 g per liter of albumin both before and during either aortic constriction or saline infusion. Results of recollection micropuncture studies in those tubules surrounded by artificially perfused capillaries were compared with results in control tubules in which the peritubular capillary flow and fluid composition were allowed to change during aortic constriction or volume expansion following saline infusion. Changes in single nephron filtration rate, fractional and absolute reabsorption induced by both aortic constriction and saline infusion were found to be qualitatively and quantitatively comparable in tubules with constant peritubular capillary microperfusion and in the control tubules with changing peritubular capillary environment due to the experimental maneuvers. Taken together, therefore, the present results indicate that with the use of the peritubular microperfusion technique no evidence is found to support a role of alteration in the peritubular environment in modulating the effect of aortic constriction or saline infusion on tubular sodium reabsorption in the rat nephron. Rather, these results provide indirect evidence in support of intraluminal factors as mediating these responses in tubular reabsorption to volume expansion and aortic constriction.Supported by the Bay Area Heart Research Committee, San Francisco, U.S.A., National Institutes of Health Grants AM 12753 and AM 05670, and the Deutsche Forschungsgemeinschaft, Bonn, Germany (Ho 347). Presented in part at the 39th Meeting of the Deutsche Physiologische Gesellschaft, Erlangen, Germany (Pflügers Arch.,332, R 32, 1972).     

Permeability of fenestrated capillaries in the isolated pig pancreas,with effects of bradykinin and histamine,as studied by simultaneous registration of filtration and diffusion capacities

Combining an isogravimetric technique and a colorimetric ‘on-line’ method (Rippe & Stage 1978). filtration capacity (CFC) and diffusion capacity (PS) were simultaneously measured in the maximally vasodilated fenestrated capillary bed of isolated, artificially perfused pancreatic glands in 12 juvenile pigs. Both CFC and PS for Cr-EDTA were about 20 times greater than in the ‘continuous’ capillary bed of skeletal muscle. With perfusate flow rates of 250 ml/min × 100 g during isogravimetry, PS-Cr-EDTA averaged 110± 10.0 (S.E.) ml/min ±100 g, and diffusion limitation occurred first at flow rates above 300 ml/min ± 100 g. CFC was independent of flow rate and averaged 0.641+0.027 ml/minx 100 g ± mmHg. The parallel augmentation of PS-Cr-EDTA and CFC in the fenestrated capillary bed compared with continuous ones seems to reflect both a higher number of capillaries per unit tissue and an increased number of ‘small pores’ per unit capillary surface, whilst the ‘large pore system’ appears to be similar. Following bradykinin or histamine infusion, results were similar to those for continuous capillaries (e.g. Rippe, Kamiya & Folkow 1978). Thus, without further vasodilatation CFC increased 3-fold while PS-Cr-EDTA increased only some 25%, and subsequent isoprenaline infusion reversed these effects. Previous studies on continuous capillaries indicate that histamine-type agents act by opening additional ‘large pores’ in the venular exchange sections (cf. Rippe & Grega 1978, Svensjo 1978). while P-adrenergic agonists block this effect. The results further suggest that the fenestrae are not involved in these bradykinin-histamine effects, but rather function as a ‘high-density, small pore population’.     

Large capillary fluid permeability in skeletal muscle and skin of man as a basis for rapid beneficial fluid transfer between tissue and blood

Our previous studies strongly indicate that the capillary filtration coefficient (CFC) in skeletal muscle and skin of man is much larger than previously believed, or about 0.050 ml min^-1 100 ml^-1 mmHg^-1. The hypothesis that this large capillary fluid permeability is a factor of primary importance for plasma volume control was approached. Experimental hypovolaemia induced by lower body negative pressure (Lbnp of 70–95 cmH₂O) was associated with a rapid net fluid gain from the studied upper arm into the circulation of 0.17 ml min^-1 100 ml^-1 tissue. The transcapillary driving force for this fluid transfer, probably caused by adrenergic adjustment of vascular resistance, with a decline of capillary pressure, was relatively small, or 1.7 mmHg on average. CFC was instead very high during LBNP, increasing from a control value of 0.054±0.004 (SE) to no less than 0.097±0.007 ml min^-1 100 ml^-1 mmHg^-1, probably reflecting an increased number of effectively perfused capillaries. It is suggested that the large capillary fluid permeability in skeletal muscle and skin of man, with large tissue mass and fluid reservoir, may be of great functional importance for plasma volume control after blood loss and also in other (patho)physiological situations. As demonstrated, it can thus permit rapid transfer of large fluid volumes into the circulation and, perhaps of special importance, with only small transcapillary driving force (capillary pressure decline). If capillary permeability were to be more limited, reasonably rapid fluid transfer instead might have required pronounced and, for tissue nutrition, necessarily undue adjustments of vascular resistance in order to cause more marked decline in capillary pressure.     

Structural evidence for counter-current flow in proximal tubules versus pertitubular capillaries in the rat kidney. Evaluation of the counter-current mechanism between the proximal convoluted tubules and the peritubular capillaries in the rat nephron

BACKGROUND: In spite of the very high exchange of water and solutes between the proximal tubules and the peritubular capillaries, very little is known about flow directions in these two interrelated structures. We therefore developed a morphological technique suitable for the quantitative evaluation of a counter-current system between the proximal convoluted tubules and the peritubular capillaries in rat renal cortex. METHODS: In male pentothal-anesthetized Wistar rats (body weight 200-250 g), India ink was injected into the aorta above the renal arteries, followed by instant freezing of the right kidney in isopentane at -165 degrees C, and subsequent freeze-substitution in alcohol. In microscopic slides from kidneys in which only 20-55% of the cortical peritubular capillary loops was filled with ink--representing the arterial end of the capillaries--and in which the proximal tubular segmentation could be identified in PAS-stained sections, the segments of the convoluted proximal tubules were quantitatively compared with regard to the presence of ink-stained and unstained peritubular capillaries in nephrons from the whole renal cortex. RESULTS: In the microscopic specimens of the five animals used both the loops from the first segment (P1) of the proximal convoluted tubule and those of the second segment (P2) were systematically packed closely together, the transitional segment (P1-2) being interposed between the groups. Around the loops of P1, 8%+/-2% of the capillaries was stained with India ink. In contrast, surrounding the P2 loops 67%+/-5% of the capillaries contained ink, significantly exceeding that for P1 (p<0.01). CONCLUSION: Throughout the rat renal cortex, the most proximal fraction of the peritubular capillaries surrounds the second segments of the proximal convoluted tubules, while the first tubular segments are surrounded by the more distal fraction of the peritubular capillaries. Consequently, the flows in the peritubular capillaries and in the proximal convoluted tubules in the rat renal cortex are systematically arranged as a counter-current system. This feature was previously identified only in superficial nephrons.     

Simultaneous measurements of capillary filtration and diffusion capacities during graded infusions of noradrenaline (NA) and 5-hydroxytryptamine (5-HT) into the rat hindquarter vascular bed

The relationships between capillary diffusion capacity (PS) for Cr-EDTA respective capillary filtration capacity (CFC) and vascular resistance during graded intraarterial infusions of NA and 5-HT into the artificially constant flow perfused rat hindquarter vascular bed were investigated. During maximal vasodilatation PS for Cr-EDTA was some 5.5-5.7 m//min × 100 g, CFC some 0.04 ml/min × mmHg × 100 g, while vascular resistance was 2.8 mmHg × ml^-1 × min × 100 g (PRU₁₀₀) and isogravimetric capillary pressure 12.8 mmHg on an average. Setting out from maximal vasodilatation, increasing doses of NA and 5-HT produced graded reductions in capillary surface area as reflected by progressive decreases in both PS for Cr-EDTA and CFC. These changes occurred simultaneously with progressive increases in both pre- and postcapillary resistances, causing elevations in both arterial and capillary hydrostatic pressures and hance in capillary fluid filtration at constant flow. Capillary hydrostatic pressure increased maximally to 45 mmHg (calculated for NA) and vascular resistance to some 21 mmHg × ml^-1 × min × 100 g on an average. PS for Cr-EDTA decreased maximally to some 0.7-1 ml/min × 100 g for both NA and 5-HT and, furthermore, the relationships between PS for Cr-EDTA and PRU₁₀₀ for NA respective 5-HT were almost identical. This was taken to indicate that capillary surface area for nutritional exchange is affected similarly by both drugs. However, the CFC-PRU₁₀₀ relationship was shifted towards some 30–50% higher CFC values for 5-HT than for NA at almost every level of vasoconstriction. This might suggest that 5-HT besides reducing capillary surface area also induces moderate increases in capillary permeability through increases in number and/or radius of large pores (gaps) (cf. Rippe, Kamiya& Folkow 1978). Even during NA-induced vasoconstriction, when virtually no changes in capillary permeability occurred, PS for Cr-EDTA was reduced to a relatively greater extent than CFC, the discrepancy being most pronounced during marked vasoconstriction. The significance of this finding is discussed.     

Large capillary fluid permeability in skeletal muscle and skin of man as a basis for rapid beneficial fluid transfer between tissue and blood.

Our previous studies strongly indicate that the capillary filtration coefficient (CFC) in skeletal muscle and skin of man is much larger than previously believed, or about 0.050 ml min-1 100 ml-1 mmHg-1. The hypothesis that this large capillary fluid permeability is a factor of primary importance for plasma volume control was approached. Experimental hypovolaemia induced by lower body negative pressure (LBNP of 70-95 cmH2O) was associated with a rapid net fluid gain from the studied upper arm into the circulation of 0.17 ml min-1 100 ml-1 tissue. The transcapillary driving force for this fluid transfer, probably caused by adrenergic adjustment of vascular resistance, with a decline of capillary pressure, was relatively small, or 1.7 mmHg on average. CFC was instead very high during LBNP, increasing from a control value of 0.054 +/- 0.004 (SE) to no less than 0.097 +/- 0.007 ml min-1 100 ml-1 mmHg-1, probably reflecting an increased number of effectively perfused capillaries. It is suggested that the large capillary fluid permeability in skeletal muscle and skin of man, with large tissue mass and fluid reservoir, may be of great functional importance for plasma volume control after blood loss and also in other (patho)physiological situations. As demonstrated, it can thus permit rapid transfer of large fluid volumes into the circulation and, perhaps of special importance, with only small transcapillary driving force (capillary pressure decline).(ABSTRACT TRUNCATED AT 250 WORDS)     

Peritubular capillary control of proximal tubule reabsorption in the rat.

Changes in peritubular capillary hydrostatic and oncotic pressures, which probably affect net interstitial pressure and, thus, the force on fluid movement across the tubule basement membrane, can modulate absolute proximal reabsorption rate (APR). To examine the relationship between APR and net interstitial pressure, we measured peritubular capillary hydrostatic and oncotic pressure, single nephron filtration rate, APR, absolute distal reabsorption (ADR), and tubular hydrostatic pressure in hydropenic, saline-loaded, and plasma-loaded rats. Net interstitial pressure in saline loading was estimated from subcapsular hydrostatic pressure and lymph protein concentration measurements. The surface area-hydraulic conductivity product of the peritubular capillary network was estimated from these measurements with a model of capillary fluid exchange in which fluid uptake was defined to be APR plus ADR. The estimated value was assumed to remain constant in all three states, and was then used to estimate net interstitial pressure in hydropenic and plasma-loaded rats. APR and net interstitial pressure correlated strongly, a finding consistent with the hypothesized role for net interstitial pressure in regulating proximal reabsorption.     

Glomerular ultrafiltration in rabbits with superficial glomeruli

The determinants of glomerular ultrafiltration in superficial glomeruli of a strain of English cross-breed rabbits have been studied using micropuncture techniques. Mean arterial blood pressure in the anaesthetised rabbits was 70±2 mmHg. The glomerular filtration rate in the kidney prepared for micropuncture was 4.4±0.4 ml/min, the filtration fraction was 22±1% and renal blood flow was 33±3 ml/min, and these values were comparable to values in conscious rabbits. Glomerular capillary pressure (P _gc) averaged 31±1 mmHg, the single-nephron glomerular filtration rate (SNGFR) averaged 25±2 nl/min, and the mean ultrafiltration pressure (calculated using the whole-kidney filtration fraction) averaged 7±1 mmHg. A net positive pressure at the efferent end of the glomerular capillaries (4.4±0.9 mmHg) indicated that a state of filtration pressure disequilibrium existed, under the experimental conditions of this study, in rabbit glomeruli. The calculated glomerular ultrafiltration coefficient (K _f) was 0.08±0.01 nl s^–1 mmHg^–1. Thus, compared to the Munich-Wistar rat, SNGFR is lower in the rabbit. This reflects the substantially lower glomerular ultrafiltration pressure in the rabbit, although this was offset partially by a higher K_f.     

Kinetics of the glomerular ultrafiltration in the rat kidney. An experimental study.

The quantitative relation between the driving forces over the glomerular membrane and the glomerular plasma flow, on the one hand, and the single glomerular filtration rate (SNGFR), on the other, is still uncertain. Micropuncture measurements on Sprague-Dawley rats made it possible to calculate the net driving force over the glomerular membrane. The single glomerular plasma flow was determined from SNGFR and the single nephron filtration fraction (SNFF). The effective plasma flow was measured with PAH for total kidney and for superficial nephrons. The mean glomerular capillary pressure was found to be 62.6 mm Hg. The results indicate a net driving force of about 13 mm Hg at the distal end of the glomerular capillary. SNGFR was found to be 14.1 nl/min-100 g. SNFF amounted to about 0.27. The filtration fractions determined with the PAH method were in the same range. The results indicate a filtration disequilibrium, in contrast to those of Brenner et al. from measurements on a mutant Wistar rat strain. The filtration fractions seemed to be the same in all glomerular populations. It is clear that the SNGFR is pressure dependent. Our earlier findings of a nonautoregulation of the blood flow through the outer glomeruli were also confirmed.     

Acute effects of C-peptide on the microvasculature of isolated perfused skeletal muscles and kidneys in rat

The C-peptide has recently been suggested to have beneficial effects in several organs and improve glycaemic control in human type I diabetes, while there were no such effects in healthy controls. The exact mechanisms behind these effects are, however, not clear. In an attempt to study the actions of C-peptide on the microvasculature in normal rats during more controlled conditions, isolated rat hindquarters and kidneys were perfused with albumin solutions in order to obtain low basal concentrations of C-peptide. In rat hindquarters, infusion of C-peptide significantly increased the capillary filtration coefficients (CFC) from 0.035±0.002 to 0.044±0.002 mL min^-1 100 g^-1 mmHg^-1 (P<0.001, n=9) and the permeability surface area product (PS) for vitamin B₁₂ from 3.48±0.29 to 4.02±0.37 mL min^-1 100 g^-1 (P<0.01, n=6). Addition of C-peptide to the perfusate during infusion of sodium nitroprusside did not induce any additional alteration of CFC or PS. The vascular resistance was slightly decreased from 2.74±0.17 to 2.64±0.17 mmHg min 100 g mL^-1 (P<0.01, n=9). These effects of C-peptide are compatible with increases in capillary surface area without alteration of the permeability per se. In isolated rat kidneys perfused at low temperature (8 °C) prepared to inhibit all metabolic processes, C-peptide induced no changes in glomerular filtration rate, total vascular resistance or fractional albumin clearance. Therefore, C-peptide causes active vasodilation of the normothermic microvasculature and hence recruitment of capillaries. These findings support the previous observations in man that C-peptide indeed has biological effects.     

Angiotensin II induced reduction of peritubular capillary diameter in the rat kidney

Summary Large peritubular capillaries were infused consecutively (20 nl · min⁻¹) in random sequence with isotonic saline and angiotensin II (20–80 ng · ml⁻¹). The diameters of the infused capillaries were measured, without knowledge of the infusate used, from colour photographs of the infused area. Angiotensin II induced a significant (p<0.001) decrease in capillary diameter (Δ=−1.2±0.2 (SE) μm and Δ=−2.1±0.2 (SE) μm with 20 ng · ml⁻¹ and 80 ng · ml⁻¹ angiotensin II infusates, respectively). This decrease was shown to be independent of external tubular compression: separate experiments in which the surrounding tubules were collapsed by injection of oil blocks yielded similar results. The possibility that the observed reduction in diameter was caused by an angiotensin II induced change in capillary permeability to the staining solution was excluded, since the angiotensin II effect was unchanged when fluorescent dextran (mol. wt. 150000) was substituted for lissamin green. These experiments indicate that peritubular capillaries contract actively when infused with angiotensin II.     

Reduced permselectivity in isolated perfused rat kidneys following small elevations of glomerular capillary pressure

A modified rat kidney preparation was used to explore how changes in hydrostatic pressure affect the permselective properties of the glomerular capillary bed. Th? maximally vasodilated kidneys of 18 rats were perfused with albumin solutions (16.7 g ^-1) at different flow rates and hence arterial pressures (P_A). One kidney in each rat was exposed to pressure elevations with the other kidney serving as a control perfused at constant P_A of about 100 mmHg. Both the vascular resistance to flow and the glomerular filtration rate (GFR 34.6 ± 2.9 ml min¹ 100 g^_1) were similar in the two kidneys at equal P_A and remained constant throughout the experiment. The ratio of albumin clearance over GFR (Θ) was initially around 0.4% at constant P_A and gradually increased during 1.5 h to reach 0.7% at the end of the experiment. A direct increase of P_A from 100 to 200 mmHg for 15 min resulted in a calculated increase of the effective glomerular filtration pressure gradient of 10–15 mmHg and in a two-fold increase ofΘ when measured at an identical P_A of 100 mmHg. Albumin clearance was almost fully normalized within 20 min similar to that observed in e.g. skeletal muscle. However, the glomerular capillary barrier seemed to be far more sensitive to elevations of hydrostatic pressure than other capillary walls which require capillary pressure increments of 60 mmHg in order to induce similar reversible changes in permeability. Therefore, we conclude that an elevated P_G:c per se induces changes of glomerular permselectivity, which may have important pathophysiological implications during conditions of proteinuria.     

Ultrastructure of the developing vascular system in the puppy kidney

The present study defined the ultrastructural features of peritubular capillary development. Two-day-old beagle puppies and adult dogs were perfused with 2.5% glutaraldehyde and routinely prepared for light and transmission electron microscopy. Some of the fixed tissue was subsequently used to make freeze-fracture replicas. The outer cortex of the puppy kidney possessed large, thick-walled vessels best termed sinusoidal capillaries instead of the small caliber vessels (peritubular capillaries) noted in the adult. These sinusoidal vessels showed extensive overlapping of the endothelium with isolated patches of fenestrae. Their luminal surfaces were irregular, owing to prominent ridges and sporadic bulges of endothelium. The basement membrane of most vessels was not present. Interstitial spaces were filled with mesenchymal cells and cells closely resembling pericytes. The diameter of the fenestrae of vessels throughout the cortex was similar; however, the number of fenestrae per micrometer of endothelium increased significantly from outer to inner cortex. Vessels of the inner cortex were also immature when compared to the adult. From these morphological findings, it was apparent that a true peritubular capillary system does not exist in the two-day-old puppy. Ultrastructural features of these vessels suggested reduced permeability characteristics.     

Influence of parathyroid hormone on glomerular ultrafiltration in the rat

Experiments were performed on 22 plasma-expanded Munich-Wistar rats to investigated the effects of parathyroid hormone (PTH) on the determinants of glomerular ultrafiltration. Mean values for single nephron filtration rate (SNGFR), glomerular plasma flow rate (QA), systemic oncotic pressure, and transglomerular hydraulic pressure difference (deltaP) were similar in acutely thyroparathyroidectomized (TPTX) rats and non-TPTX rats. Nevertheless, the glomerular capillary ultrafiltration coefficient (Kf) was uniformly higher in TPTX rats (greater than 0.113 +/- 0.005 (SE) nl/(s.mmHg)] than in non-TPTX controls (0.088 +/- 0.005). In TPTX rats, infusion of a submaximal dose (1 U/kg per min) of PTH resulted in significant decreases in SNGFR at constant QA and deltaP, due primarily to return of Kf to non-TPTX levels. Infusion of 10 U/kg per min of PTH to non-TPTX rats further reduced Kf, on average to 0.042 +/- 0.001 nl/(s.mmHg), leading to further reduction in SNGFR, whereas QA and deltaP again remained constant. These findings suggest that PTH may play an important role in modulating Kf, and consequently, SNGFR.     

Effects of lysine on bicarbonate and fluid absorption in the rat proximal tubule

The effects of lysine on bicarbonate and fluid reabsorption in the rat proximal tubule were studied by luminal and capillary perfusion in situ. The proximal tubule and peritubular capillaries were perfused with bicarbonate Ringer solution containing [14C]inulin. The rate of bicarbonate reabsorption (JHCO3) was estimated to be 124 +/- 9.5 peq.min-1.mm-1 using a pH membrane glass electrode. The rate of net fluid reabsorption (Jv) was 2.6 +/- 0.21 nl.min-1.mm-1. When 10 mM L-lysine was added to the luminal perfusate, a 35% reduction in JHCO3 and no change in Jv were observed. Increase of L-lysine concentration in the luminal perfusate to 20 mM did not reduce JHCO3 further nor did it influence Jv.l When 10 mM L-lysine was added to the capillary perfusate, a 13% reduction in JHCO3 was observed (NS). Increase of lysine concentration in the capillary perfusate to 20 mM significantly reduced JHCO3 by 26% (P less than 0.01). There was no significant change in Jv under both conditions. The effect of L-lysine in the lumen was related to its reabsorption kinetics, D-Lysine, which was not reabsorbed significantly, did not affect bicarbonate reabsorption in the proximal tubule. These results indicate that the inhibitory effect of L-lysine is related to the entry of lysine into the cell from the lumen.