Histochemical studies on the mechanism of macromolecule leakage across the glomerular capillary wall. Barrier effect of the anionic groups of the capillary wall against the serum protein leakage

For the purpose of revealing the barrier effect of the anionic groups of glomerular capillary wall against the serum protein leakage, morphologic and histochemical observations were made on the rat kidney perfused in situ with three kinds of cationic macromolecules different in chemical characteristics followed by blood flow restoration. The polyethyleneimine perfusion resulted in the complete disapperance of ionized anionic groups of glomerular capillary and the massive protein leakage through glomeruli by blood flow restoration. Cationic ferric colloid perfusion induced moderate protein leakage, and avidin perfusion was less in neutralization effect of anionic groups and the protein leakage was of least. The protein leakage from glomeruli, however, was stopped or markedly suppressed soon after the blood flow restoration by the newly formed functioning anionic barrier probably by some particular serum protein deposition. The findings indicate that the deionization of the glomerular capillary wall will not be responsible for the persistent albuminuria.     

Localization and distribution of anionic charges in the glomerular mesangium of normal and nephrotic rats

Sulfated glycosaminoglycans and sialoglycoproteins are thought to play a pivotal role in the glomerular capillary wall barrier to filtration since these anionic charged elements are important in the maintenance of capillary wall integrity and constitute a charge-selective filter. The development of proteinuria in puromycin aminonucleoside (PAN) nephrosis is associated with polyanion loss from the glomerular capillary wall structures. Since in PAN nephrosis the permeability of the mesangial area to plasma proteins and tracer substances has also been shown to be increased, the purpose of this study was to analyse the localization and distribution of anionic charges in the glomerular mesangium in this experimental model. Glycosaminoglycans were labeled by perfusion of the kidneys with ruthenium red solution (RR). Electron microscopic examination revealed the presence of distinct small RR granules ("anionic sites") in the mesangial intercellular matrix substance and in the laminae rarae of the glomerular basement membrane (GBM). The center-to-center spacing of the granules was measured and a frequency distribution of intervals in different interval classes was constructed. In normal glomeruli the anionic sites in the mesangial matrix showed a distribution pattern identical to the GBM with a maximal interval incidence at the 31-40 nm class. In nephrotic rats anionic site distributions in matrix and GBM did not change significantly. Sialoglycoproteins were labeled with colloidal iron (CI). In PAN nephrosis a decrease of CI binding was observed at the epithelial-basement membrane junction of the glomerular capillary wall. However, CI labeling of the mesangial matrix and mesangial cell membranes did not differ from that of normal glomeruli.(ABSTRACT TRUNCATED AT 250 WORDS)     

The anionic barrier system in the mesonephric renal glomerulus of the arctic lamprey,Entosphenus japonicus (Martens) (Cyclostomata)

Summary To examine the selective permeability of the nephrons of lower vertebrates, the permeability of the glomerulus in the kidney of an arctic lamprey, Entosphenus japonicus (Martens), to native anionic ferritin or cationized ferritin was studied by observing the distribution of ionized anionic groups in renal tissues. The cationized ferritin molecules injected into the dorsal aorta penetrated rapidly into the glomerular basement membrane layer through fenestrae present in the capillary endothelium and were subsequently excreted into the urinary spaces via the interstices between foot processes of the visceral epithelial cells. Native anionic ferritin, on the other hand, passed only minimally through the capillary wall. Cytochemical staining of fixed tissue or perfusion of the kidney in situ with cationic cacodylate-iron colloid revealed that the ionized anionic groups of acid mucopolysaccharides were distributed on both the luminal and abluminal surfaces of endothelial cells, and in the thick fibrous lamina rara interna of the glomerular basement membrane; they were especially dense on the surfaces of visceral epithelial cells and their foot processes. These results suggest that the mesonephric glomerulus of the arctic lamprey possesses a functionally well developed anionic barrier system comparable to that of the mammalian metanephric glomerulus.     

Effect of theophylline on the glomerular pathway of ferritin macromolecules in rats]

The present microscopic study evaluates the quantitative variations of ferritin particules density within the glomerular ultrastructures after theophyllin perfusion in the Rat. The ferritin particules density increases 3,65 times in the glomerular basement membrane and decreases 3,28 times in the glomerular capillary lumen. So, theophyllin increases considerably the glomerular pathway of the protein macromolecules. This results confirm the increased volumic flow (Jv) and macro-solutes flow (Js') noted with clearance methods and urinary excretion studies.     

Role of molecular charge in glomerular permeability. Tracer studies with cationized ferritins

Mouse kidneys were perfused with Krebs-Ringer bicarbonate buffer (KRB) containing native, anionic horse spleen ferritin or various cationized derivatives, and the glomerular localization of the probe molecules determined by electron microscopy. Ferritins cationic with respect to the medium (KRB, pH 7.45) accumulated in the subendothelial layers of the glomerular basement membrane (GBM) in amounts far exceeding those observed with anionic ferritins, the degree being greater for the more cationized derivatives. Strongly cationized ferritins, in addition permeated the full thickness of the GBM in considerable amounts, but appeared to be retarded from entry into the urinary spaces at the level of the filtration slits. Very strongly cationized derivatives adhered to glomerular endothelium and GBM and formed aggregates in the outer layers of the latter. The results suggest that intrinsic negative charges are present in the GBM and endothelium, and that the barrier function of the glomerular capillary wall may be ascribed in part to its electrophysical properties.     

Studies of the permeation properties of glomerular basement membrane: cross-linking renders glomerular basement membrane permeable to protein.

Cross-linking glomerular basement membrane (GBM) has been shown to render it more permeable to protein. Isolated pig GBM was cross-linked with dimethylmalonimidate which reacts selectively with lysine epsilon-NH2 groups or with glutaraldehyde, a less selective cross-linking agent. Studies of the ultrafiltration properties of these materials in vitro using cytochrome c, myoglobin, bovine serum albumin and immunoglobulin showed that cross-linking had markedly increased solvent and protein fluxes as compared with native membranes particularly at higher pressures. Filtration studies with serum demonstrated that the cross-linked membranes were more permeable to serum proteins. Thickness measurements under pressure indicated that cross-linked membrane was less compressed than native membrane as pressure was increased. Pore theory did not provide a suitable model for analysis of the results, but analysis of the results using the fibre-matrix hypothesis indicated that cross-linking had the effect of bundling together the fibres (type IV collagen) in the GBM matrix. The effect of cross-linking on filtration could be explained by a combination of contraction of the membrane, fibre bundling and increased rigidity compared with native membrane. Cross-linking of GBM might lead to long-term damage of the glomerular capillary wall in nephritis, so promoting proteinuria.     

The endoendothelial fibrin lining as the crucial barrier and the role of fibrin(ogenin) gels in controlling transcapillary transport

The interface between the two portions of the 'vessel-blood organ', viz., the vessel wall and the circulating blood, is considered by the author to be the endoendothelial fibrin lining (EEFL). The view that the endothelium, consisting of the endothelial cells and the interendothelial cement substance, is the primary filtration barrier in capillary permeability (CP) is no longer tenable. There is considerable evidence that the primary barrier is an endocapillary protein layer, originally postulated by Danielli in 1940. Copley considered this layer to be identical with the EEFL formed in the more or less immobile portion of the plasmatic zone in close proximity to the vessel wall. Processes of fibrin formation and fibrinolysis can occur there homeostatically, undisturbed by the flow of blood. The fibrinopeptides and plasminopeptides, freed at this site by the conversion of fibrinogen to fibrin and of plasminogen to plasmin, respectively, were reported by Copley et al in 1966 to augment CP. These peptides thus take part in the steadily occurring normal physiological CP. This is facilitated by the porosity of the EEFL due to the network or gel structure of fibrin strands. The author's concept that the EEFL acts as the primary barrier, controlling transendothelial transport and transport across the basement membrane (BM), is discussed on the basis of older and recent findings by several investigators. In particular, the BM is dealt with in some detail as a barrier. Emphasis is placed on the existence of fibrin as a main constituent of the BM, hitherto not generally known. This was demonstrated by direct evidence in the production of (non-thrombocytopenic) vascular purpura with fibrin antiserum. Numerous tiny foci of fibrin(ogenin) gels are expected to stud the BM. Augmented capillary fragility (CF) due to increased fibrinolysis of many of these focal fibrin gels result in petechial hemorrhages. CF and CP are physical properties of the blood capillary wall which behave antagonistically and are controlled by fibrin formation and fibrinolysis, steadily occurring in the vascular layers including the BM. This barrier secures the integrity of the capillary wall by preventing extravasation of blood or hemorrhages. New experimental approaches to verify the detection of fibrin in the microstructure of the capillary wall are proposed. Moreover, hemorheological experimentation, models and treatments are needed to establish whether or not the EEFL is the crucial, critical barrier in CP, as proposed.     

Glomerular lysozyme binding in protein-overload proteinuria

Binding of the cationic molecule lysozyme to the glomerular basement membrane and to the glomerular epithelial cell coat was investigated in the glomerulus of normal female Wistar rats and in rats in which heavy proteinuria was induced by the daily administration of 1 g of bovine serum albumin. In normal rats the binding of lysozyme to the anionic groups in the glomerular basement membrane and the cell coat had no effect on the ultrastructure of the glomerular epithelial cell, in particular the foot processes were unchanged. In the proteinuric rats the lysozyme-binding to the glomerular basement membrane and the epithelial cell coat was completely lost in the damaged glomeruli. In the apparently normal glomeruli present in these proteinuric animals binding was similar to that seen in normal rats. These results suggest that in protein-overload proteinuria there is a loss of glomerular anion and hence a reduction in the glomerular charge barrier. This may account, at least in part, for the increased glomerular leak of negatively charged serum albumin in this experimental model of proteinuria.     

Studies of the permeation properties of glomerular basement membrane: cross-linking renders glomerular basement membrane permeable to protein

Cross-linking glomerular basement membrane (GBM) has been shown to render it more permeable to protein. Isolated pig GBM was cross-linked with dimethylmalonimidate which reacts selectively with lysine ?-NH₂ groups or with glutaraldehyde, a less selective cross-linking agent. Studies of the ultrafiltration properties of these materials in vitro using cytochrome c, myoglobin, bovine serum albumin and immunoglobulin showed that cross-linking had markedly increased solvent and protein fluxes as compared with native membranes particularly at higher pressures. Filtration studies with serum demonstrated that the cross-linked membranes were more permeable to serum proteins. Thickness measurements under pressure indicated that cross-linked membrane was less compressed than native membrane as pressure was increased. Pore theory did not provide a suitable model for analysis of the results, but analysis of the results using the fibre-matrix hypothesis indicated that cross-linking had the effect of bundling together the fibres (type IV collagen) in the GBM matrix. The effect of cross-linking on filtration could be explained by a combination of contraction of the membrane, fibre bundling and increased rigidity compared with native membrane. Cross-linking of GBM might lead to long-term damage of the glomerular capillary wall in nephritis, so promoting proteinuria.     

Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging

Pericytes play a key role in the development of cerebral microcirculation. The exact role of pericytes in the neurovascular unit in the adult brain and during brain aging remains, however, elusive. Using adult viable pericyte-deficient mice, we show that pericyte loss leads to brain vascular damage by two parallel pathways: (1) reduction in brain microcirculation causing diminished brain capillary perfusion, cerebral blood flow, and cerebral blood flow responses to brain activation that ultimately mediates chronic perfusion stress and hypoxia, and (2) blood-brain barrier breakdown associated with brain accumulation of serum proteins and several vasculotoxic and/or neurotoxic macromolecules ultimately leading to secondary neuronal degenerative changes. We show that age-dependent vascular damage in pericyte-deficient mice precedes neuronal degenerative changes, learning and memory impairment, and the neuroinflammatory response. Thus, pericytes control key neurovascular functions that are necessary for proper neuronal structure and function, and pericyte loss results in a progressive age-dependent vascular-mediated neurodegeneration.     

Circulating Glycated Albumin and Glomerular Anionic Charges

Aiming to discern the mechanisms by which circulating glycated albumin alters the glomerular filtration properties that lead to glomerular dysfunction in diabetes, the authors studied the distribution and densities of anionic charges through the rat glomerular wall upon intravascular infusion of Amadori products, as well as in various conditions of increased glomerular permselectivity. Polylysine-gold was used as the probe to reveal the anionic charges. The study was carried on renal tissue sections of bovine serum albumin (BSA)- and glycated BSA–injected, normoglycemic animals. Results were generated through morphometrical evaluations of the gold labeling. Changes in glomerular anionic distribution were corroborated on renal tissue sections of short- and long-term diabetic rats and of normal newborn rats, situations known for abnormal glomerular filtration. Altered renal function in these conditions was clearly associated with changes in glomerular anionic charges. On the other hand, the infusion of glycated albumin in the circulation of normal rats, though altering glomerular filtration properties, did not modify the distribution and density of the polylysine-gold labeling through the glomerular basement membrane. Thus, anionic charges seem not to be the factor involved in the early changes of glomerular permeability induced by circulating glycated albumin.     

Arteriovenous shunting and regional blood flow in myocutaneous island flaps: an experimental study in pigs

In eight pigs, total blood flow, regional capillary blood flow distribution, and arteriovenous (AV) shunting were studied during the first 4 postoperative hours after elevation of a myocutaneous rectus abdominis island flap. Capillary blood flow and AV shunting were measured using radioactive microspheres before flap creation and 1 and 4 hours after surgery. Total blood flow, measured continuously as venous outflow, increased in the first postoperative hour (p less than 0.05). Elevation of the flap caused a slight decrease in skin capillary blood flow (p less than 0.05), whereas muscular capillary blood flow increased (p less than 0.01). AV shunting accounted for 50 percent of the total flap blood flow, whereas it was negligible in the abdominal wall prior to flap elevation. Thus stalk blood flow, skin appearance, and skin temperature may be poor indicators of nutritional capillary perfusion. However, the clinical and nutritional consequences of these findings remain to be established.     

Cationic gold staining of glomerular anionic sites in archived tissue, reprocessed from paraffin wax into LR gold resin

Summary Glomerular capillary wall anionic sites have been demonstrated by cationic gold staining of archived renal biopsy tissue (up to 10 years old), obtained from six patients, originally embedded in paraffin wax, and subsequently reprocessed into LR gold resin. The staining patterns at pH 2.5 and pH 7.0, demonstrating different glomerular basement membrane (GBM) anionic constituents, were compared in three patients from whom tissue directly processed into LR gold and reprocessed tissue was available. Ultrastructural preservation was poorer and shrinkage artefact greater in paraformaldehyde-lysine periodate (PLP) as opposed to formol saline-fixed reprocessed tissue. However, GBM anionic site expression was well preserved, or even enhanced (lamina rara externa, pH 7.0) in reprocessed tissue, using either fixative. Although it may not be possible to compare subtle changes in anionic site distribution in variously fixed and processed tissues, due to these artefacts, the technique enables retrospective study of charge status in archived material from disease groups in which there are distinct anionic site aberrations.     

Different mechanisms influencing permeation of PDGF-AA and PDGF-BB across the blood-brain barrier

Platelet-derived growth factor (PDGF) exerts neurotrophic and neuromodulatory effects on the CNS. To determine the permeability of the blood-brain barrier (BBB) to PDGF, we examined the blood-to-brain influx of radioactively labeled PDGF isoforms (PDGF-AA and PDGF-BB) by multiple-time regression analysis after intravenous (i.v.) injection and by in-situ perfusion, and also determined the physicochemical characteristics which affect their permeation across the BBB, including lipophilicity (measured by octanol:buffer partition coefficient), hydrogen bonding (measured by differences in octanol : buffer and isooctane : buffer partition coefficients), serum protein binding (measured by capillary electrophoresis), and stability of PDGF in blood 10 min after i.v. injection (measured by HPLC). After i.v. bolus injection, neither 125I-PDGF-AA nor 125I-PDGF-BB crossed the BBB, their influx rates being similar to that of the vascular marker 99mTc-albumin. 125I-PDGF-AA degraded significantly faster in blood than 125I-PDGF-BB. PDGF-BB, however, was completely bound to a large protein in serum whereas PDGF-AA showed no binding. Thus, degradation might explain the poor blood-to-brain influx of PDGF-AA, whereas protein binding could explain the poor influx of circulating PDGF-BB. Despite their lack of permeation in the intact mouse, both 125I-PDGF-AA and 125I-PDGF-BB entered the brain by perfusion in blood-free buffer, and the significantly faster rate of 125I-PDGF-AA than 125I-PDGF-BB may be explained by the lower hydrogen bonding potential of 125I-PDGF-AA. Thus, the lack of significant distribution of PDGF from blood to brain is not because of the intrinsic barrier function of the BBB but probably because of degradation and protein binding. Information from these studies could be useful in the design of analogues for delivery of PDGF as a therapeutic agent.     

Vasomotion in critically perfused muscle protects adjacent tissues from capillary perfusion failure

We analyzed the incidence and interaction of arteriolar vasomotion and capillary flow motion during critical perfusion conditions in neighboring peripheral tissues using intravital fluorescence microscopy. The gracilis and semitendinosus muscles and adjacent periosteum, subcutis, and skin of the left hindlimb of Sprague-Dawley rats were isolated at the femoral vessels. Critical perfusion conditions, achieved by stepwise reduction of femoral artery blood flow, induced capillary flow motion in muscle, but not in the periosteum, subcutis, and skin. Strikingly, blood flow within individual capillaries was decreased (P < 0.05) in muscle but was not affected in the periosteum, subcutis, and skin. However, despite the flow motion-induced reduction of muscle capillary blood flow during the critical perfusion conditions, functional capillary density remained preserved in all tissues analyzed, including the skeletal muscle. Abrogation of vasomotion in the muscle arterioles by the calcium channel blocker felodipine resulted in a redistribution of blood flow within individual capillaries from cutaneous, subcutaneous, and periosteal tissues toward skeletal muscle. As a consequence, shutdown of perfusion of individual capillaries was observed that resulted in a significant reduction (P < 0.05) of capillary density not only in the neighboring tissues but also in the muscle itself. We conclude that during critical perfusion conditions, vasomotion and flow motion in skeletal muscle preserve nutritive perfusion (functional capillary density) not only in the muscle itself but also in the neighboring tissues, which are not capable of developing this protective regulatory mechanism by themselves.     

Glomerular endothelium: a porous sieve and formidable barrier

The glomerular capillary endothelium is highly specialized to support the selective filtration of massive volumes of plasma. Filtration is driven by Starling forces acting across the glomerular capillary wall, and depends on its large surface area and extremely high water permeability. Glomerular endothelial cells are extremely flat and perforated by dense arrays of trans-cellular pores, the fenestrae. This phenotype is critical for the high glomerular water permeability and depends on podocyte-derived VEGF, as well as TGF-beta. Endothelial cell-derived PDGFB, in turn, is necessary for the establishment of mesangial cells, which sculpt the glomerular loop structure that underlies the large filtration surface area. In pre-eclampsia, inhibition of the VEGF- and TGF-beta signaling pathways leads to endothelial swelling and loss of fenestrae, reducing the glomerular filtration rate. Similarly, in the thrombotic microangiopathies, glomerular endothelial cell injury coupled with inappropriate VWF activation leads to intracapillary platelet aggregation and loss of the flat, fenestrated phenotype, thus reducing the glomerular filtration rate. Normally, a remarkably small fraction of albumin and other large plasma proteins passes across the glomerular capillary wall despite the massive filtration of water and small solutes. An elaborate glycocalyx, which covers glomerular endothelial cells and their fenestrae forms an impressive barrier that, together with other components of the glomerular capillary wall, prevents loss of plasma proteins into the urine. Indeed, microalbuminuria is a marker for endothelial glycocalyx disruption, and most forms of glomerular endothelial cell injury including pre-eclampsia and thrombotic microangiopaties can cause proteinuria.     

Intermittent hypoxia modulates nitric oxide-dependent vasodilation and capillary perfusion during ischemia-reperfusion-induced damage

The microvascular function of nitric oxide (NO) during ischemia-reperfusion (I/R) in intermittent hypoxia (IH)-pretreated hamsters was analyzed using 20 mg/kg of the nonselective NO inhibitor N(omega)-nitro-l-arginine methyl ester (l-NAME) and 5 mg/kg of the preferential inducible NO inhibitor S-methylisothiourea sulphate (SMT) injected before I/R. Studies were made in the hamster cheek pouch microcirculation (intravital fluorescence microscopy). IH consisted of 6 min of 8% O(2) breathing followed by 6 min of 21% O(2) for every 8 h for 21 days. Normoxia controls (NCs) were exposed to room air for the same period. The effects were characterized in terms of systemic hemodynamics, diameter, flow, wall shear stress in arterioles, capillary perfusion, and the concentrations of thiobarbituric acid-reactive substances (TBARS) and plasma NO, assessed as nitrite/nitrate (NOx) levels. IH did not change arterial blood pressure and increased hematocrit and shear stress. IH increased NOx and TBARS levels and reduced arterial diameter, blood flow, and capillary perfusion versus the NC. Conversely, TBARS and NOx were lower during I/R in IH-pretreated hamsters, resulting in vasodilation and the increase of capillary perfusion and shear stress. After IH, capillary perfusion was reduced by 24% (2.3%) and enhanced by 115% (1.7%) after I/R (P < 0.05). Both modalities of NO blockade decreased NOx generation and increased TBARS versus IH. l-NAME and SMT induced a significant decrease in arteriolar diameter, blood flow, and capillary perfusion (P < 0.05). l-NAME enhanced TBARS more than SMT and aggravated I/R damage. In conclusion, we demonstrated that preconditioning with IH greatly reduces oxidative stress and stimulates NO-induced vasodilation during I/R injury, thus maintaining capillary perfusion.     

Effect of molecular charge on choroid-plexus permeability: Tracer studies with cationized ferritins

Summary The permeability of the choroid plexus and renal glomerulus to intravenously injected native, anionic ferritin and various cationic ferritin derivatives was studied in normal rats by electron microscopy. In both structures, anionic, native ferritin was largely confined to the circulatory compartment while the cationic forms penetrated and accumulated within the filtration barriers. In the choroid plexus, cationic ferritin concentrated in relationship to the endothelial fenestrations and the subendothelial basal lamina region. In the glomerulus, there was also an inner concentration of cationic tracer and, in addition, an aggregation of tracer along the outer, subepithelial portion of the basal lamina. The results indicate that the localization of tracer within the filtration barrier of both the choroid plexus and renal glomerulus is directly related to the tracer's isoelectric point. The findings suggest that the choroid plexus, like the glomerulus, contains fixed anionic groups within the capillary wall which influence its permeability.     

Hemodynamic changes in the kidney in a pediatric rat model of sepsis-induced acute kidney injury

Sepsis is a leading cause of acute kidney injury (AKI) and mortality in children. Understanding the development of pediatric sepsis and its effects on the kidney are critical in uncovering new therapies. The goal of this study was to characterize the development of sepsis-induced AKI in the clinically relevant cecal ligation and puncture (CLP) model of peritonitis in rat pups 17-18 days old. CLP produced severe sepsis demonstrated by time-dependent increase in serum cytokines, NO, markers of multiorgan injury, and renal microcirculatory hypoperfusion. Although blood pressure and heart rate remained unchanged after CLP, renal blood flow (RBF) was decreased 61% by 6 h. Renal microcirculatory analysis showed the number of continuously flowing cortical capillaries decreased significantly from 69 to 48% by 6 h with a 66% decrease in red blood cell velocity and a 57% decline in volumetric flow. The progression of renal microcirculatory hypoperfusion was associated with peritubular capillary leakage and reactive nitrogen species generation. Sham adults had higher mean arterial pressure (118 vs. 69 mmHg), RBF (4.2 vs. 1.1 ml·min(-1)·g(-1)), and peritubular capillary velocity (78% continuous flowing capillaries vs. 69%) compared with pups. CLP produced a greater decrease in renal microcirculation in pups, supporting the notion that adult models may not be the most appropriate for studying pediatric sepsis-induced AKI. Lower RBF and reduced peritubular capillary perfusion in the pup suggest the pediatric kidney may be more susceptible to AKI than would be predicted using adults models.     

Cardiac edema in dogs: distribution of renal blood flow and glomerular filtrate.

The injection of Freund's adjuvant into the pericardial sac of 29 dogs resulted in chronic pericardial tamponade with persistent sodium retention. Micropuncture, clearance, and radioactive microsphere experiments were initiated 6--13 days after pericardial injection and 60 min after pericardiocentesis. Pericardiocentesis increased sodium excretion (from 12.2 to 41.3 microequiv./min) and mean arterial pressure (+ 20 mmHg (1 mmHg = 133.322 Pa)). Central venous pressure decreased 6.5 mmHg, as did hematocrit (from 45.7 to 39.8%) and plasma protein concentration (from 5.88 to 5.15 g%). Pericardiocentesis had no significant effect on renal blood flow (RBF), nor plasma flow. Redistribution of glomerular filtrate was suggested by the observation that superficial nephron glomerular filtration rate increased (from 91 to 108 nL/min) while glomerular filtration rate remained unaltered. Determination of intrarenal distribution of RBF revealed that cortical blood flow also distributed superficially. A significant increase in the fraction of RBF perfusing zone 1 (outer cortex) and a decrease in fractional perfusion of zones 2, 3 and 4 (juxtamedullary cortex) were observed in each experiment following pericardiocentesis. RBF distribution examined in a series of six animals prior to and during the development of pericardial tamponade showed the opposite effect. These results indicate that pericardiocentesis causes redistribution of both glomerular filtrate and RBF to superficial nephrons. The development of pericardial tamponade was associated with increased fractional juxtamedullary blood flow. These changes may have been the result of altered blood pressure, hematocrit, plasma protein concentration, or altered renal resistance.