Effect of Elevated Interstitial Pressure on the Renal Cortical Hemodynamics

The influence of renal interstitial pressure on the resistance pattern within the superficial cortical vasculature has been investigated from determinations of I) the glomerular blood flow with a modified microsphere technique and 2) the intravascular hydrostatic pressures. Interstitial pressure was monitored via a 50 μm PVC-catheter placed into the subcapsular interstitial space. Two conditions were analyzed viz. a) elevation of iiretheral pressure to 20 mm Hg and b) venous stasis to 10–15 mm Hg. Both conditions produced an increase in the interstitial pressure from 1–2 mm Hg to about 5 mm Hg as well as an increased hilar lymph flow and protein flow of about the Same size. The vascular reactions were different, however. Urethcral stasis (but not the stasis of a single nephron) produced a decreased resistance in the afferent arteriolae with a concomitant increase in the pressures in the glomerular capillaries, and the peritubular capillary network. In contrast, venous stasis produced only small changes in the parameters studied but for the obvious rise in the peritubular capillary pressure. The results suggest that factors other than the interstitial pressure are governing the afferent vascular tone; the tubular wall tension might he one of these factors.     

Effect of Hematocrit on pressure-flow relations for perfused isolated lobes of the canine lung

Summary The effect of hematocrit on pressure-flow relations for the pulmonary circulation was studied by means of an isolated lung preparation. Lobes taken from mongrel dogs were perfused with autologous blood of hematocrits ranging from 23 to 75. The apparatus was of a closed circuit type, consisting of the lobe being perfused by means of a roller pump so that a series of steady flows could be obtained. Transpulmonary pressure was imposed by positive inflation. Venous pressure, fixed by the distal liquid overflow, was maintained at+10 cm H₂O while alveolar pressure was +5 cm H₂O. Thus, for most of the parenchyma conditions were consistent with Zone III as described by Westet al. The arterio-venous pressure difference was varied between 3 and 50 cm H₂O.For comparison, pressure-flow relations were obtained concurrently with a capillary viscometer capable of attaining wall shear rates of less than 1 sec^–1.In 12 alterations of hematocrit (concentrations and dilutions) with 9 lobes it was found without exception that (1) increasing the hematocrit causes a shift of the pressure-flow curve in the direction of decreased flow and (2) decreasing the hematocrit caused a shift of the curve in the direction of increased flow. Analysis showed these changes to be statistically significant. Some evidence was also found that pressure-flow curves become more non-linear as hematocrit is increased.Supported in part by financial aid from the High Authority of the European Coal and Steel Community and the Délégation Générale à la Recherche Scientifique (Grant No. 66-00-442).     

Pulmonary interstitial resistance

The mechanical properties of the perivascular interstitium surrounding large pulmonary blood vessels are defined in terms of interstitial fluid pressure, interstitial compliance, and interstitial hydraulic resistance. Interstitial pressure is one of the main forces which determine liquid filtration across the microvascular barrier. Interstitial compliance is a measure of the ability of the interstitium to swell with hydration which increases interstitial pressure and reduces the filtration rate. Interstitial pressure and compliance are functions of the elastic properties of the surrounding lung parenchyma and the vessel wall. Solid continuum mechanics are used to describe the behavior of the lung parenchyma. The transport properties of the interstitium are described in terms of a porous material whose fluid resistance is determined by a permeability constant. The dynamics of interstitial fluid are governed by the coupling of the flow with the elastic environment. An electrical analog model is developed to predict the growth of interstitial fluid cuffs during edema formation.     

Resolution of increased permeability pulmonary edema in rats.

The rate and sequence of interstitial and alveolar fluid removal from the lung after the occurrence of pulmonary edema were examined. Rats were given intraperitoneal injections of 20 mg/kg alpha-naphthylthiourea (ANTU), resulting in an increased permeability edema with alveolar flooding. Animals were killed at intervals between 2 and 48 hours after ANTU for the gravimetric determination of extravascular lung water (Qwl/dQl) and histologic study of the lung. Interstitial fluid volume was quantified by a morphometric technique. The assumptions were made that edema fluid equaled the experimental Qwl/dQl minus the normal Qwl/dQl, and that the edema fluid volume equaled the sum of interstitial and alveolar fluid volume. It was found that between 2 and 4 hours after the induction of pulmonary edema, fluid was removed from the alveolar space faster than it was removed from the interstitial space. Between 4 and 48 hours after ANTU, the fluid removal rate from both compartments was much slower, and interstitial fluid was removed at a faster rate than alveolar fluid. It is hypothesized that the later phase of fluid removal from the lung is dependent on the removal of protein.     

Catecholamine-induced pulmonary edema and pleural effusion in rats--alpha- and beta-adrenergic effects

We investigated the contribution of alpha- and beta-adrenergic pathways to catecholamine-induced pulmonary edema and the role of pleural effusion in preventing alveolar edema. Female Sprague-Dawley rats received continuous intravenous infusion of norepinephrine and of separate alpha- or beta-adrenergic stimulation over 6-24 h. We performed heart catheterization in vivo and excised post mortem lung tissue for histological analysis. Interleukin (IL)-6 and total protein concentrations were determined in serum, pleural fluid (PF) and bronchoalveolar lavage fluid. alpha-Adrenergic treatment increased right ventricular systolic pressure (RVSP) and total peripheral resistance (TPR) and caused severe alveolar edema associated with IL-6 activation in serum and diffuse pulmonary inflammation. PF amounts were moderate (0.9+/-0.2 ml). beta-Adrenergic stimulation also increased RVSP but decreased TPR. Interstitial but not alveolar edema and focal inflammation without IL-6 activation developed. Large PF amounts (6.2+/-1.5 ml) occurred which were considered to prevent alveolar edema. We conclude that both alpha- and beta-adrenergic stimulation contribute to pulmonary fluid shifts in rats, but alpha-adrenergic pathways cause more acute and more severe lung injury than beta-adrenergic mechanisms.     

5‐Hydroxytryptamine‐induced microvascular pressure transients in lungs of anaesthetized rabbits

We determined lung microvascular pressure transients induced by 5‐hydroxytryptamine (5HT), by the micropuncture technique. We mechanically ventilated anaesthetized (halothane 0.8%), open‐chested rabbits, in which we recorded pulmonary artery (PA), left atrial (LA) and carotid artery pressures and cardiac output. For 4‐min periods of stopped ventilation, we constantly inflated the lung with airway pressure of 7 cmH₂O, then micropunctured the lung to determine pressures in arterioles and venules of 20–25 μm diameter. An intravenous bolus infusion of 5HT (100 μg), increased total pulmonary vascular resistance by 59%. Prior to 5HT infusion, the arterial, microvascular and venous segments comprised 30, 50 and 19% of the total pulmonary vascular pressure drop, respectively. However 14 s after 5HT infusion, the PA‐arteriole pressure difference (arterial pressure drop) increased 46%, while the venule‐LA pressure difference (venous pressure drop) increased >100%. The arteriole–venule pressure difference (microvascular pressure drop) was abolished. The increase in the arterial pressure drop was maintained for 4.8 min, whereas the increased venous pressure drop reverted to baseline in <1 min. We conclude that in the rabbit lung in situ, a 5HT bolus causes sustained arterial constriction and a strong but transient venous constriction.     

Protein composition of lung fluids in acute alloxan edema in dogs.

In 11 anesthetized dogs with acute alloxan-induced pulmonary edema, we measured the protein composition of 1-mul samples of plasma, free interstitial fluid, alveolar fluid, and airway fluid. We obtained plasma and airway fluid at regular intervals as edema developed. We sampled alveolar fluid by pleural micropuncture in the unfrozen, excised lung and free interstitial fluid from perivascular cuffs in the frozen, excised lung. The average (+/- 1 SD) total protein concentration of plasma was 4.9 +/- 0.6, airway fluid 4.4 +/- 0.7, free interstitial fluid 4.9 +/- 0.7, and alveolar fluid 5.2 +/- 0.8 g/100 ml. The average fractions of albumin were 0.42 +/- 0.05, 0.50 +/- 0.05, 0.49 +/- 0.06, and 0.49 +/- 0.07, respectively. By paired analysis, the protein concentration of interstitial fluid was not significantly different from alveolar fluid. The protein concentration of airway fluid was significantly less than that in interstitial and alveolar fluid. The albumin fraction of the three lung fluids was identical but significantly different from plasma. We conclude that in alloxan-induced pulmonary edema the lung fluids contain high concentrations of protein and the alveolar epithelial membrane becomes freely permeable to protein molecules.     

Evaluation of the ‘stretched pore phenomenon’ in isolated rat hindquarters

RIPPE, B., HARALDSSON, B., FOLKOW, B. 1985. Evaluation of the ‘stretched pore phenomenon’ in isolated rat hindquarters. Acta Physiol Scand 125 , 453–459. Received 5 March 1985, accepted 7 May 1985. ISSN 0001–6772. Department of Physiology, University of Göteborg, Sweden. In order to study the changes in capillary permeability occurring upon marked elevations in microvascular pressure, capillary filtration coefficient (CFC) and diffusion capacity (PS) for Cr-EDTA were repeatedly measured ‘on-line’ before and after brief periods (3 min) of large venous pressure (P_v) elevations in maximally vasodilated perfused rat hindquarters. First at P_v's ≥ 55 mmHg, increases in CFC and Ps-Cr-EDTA were observed immediately after the pressure elevations. While the CFC increases were then always pronounced (up to 4- to 5-fold), the concomitant increases in PS-Cr-EDTA were small (at most 30–40%). For P_v≥ 55 mmHg there was a rough proportionality between P_v and CFC. While PS for Cr-EDTA showed little reversibility with time upon P_v normalization, CFC was usually almost completely reversed after 10–20 min. The mentioned CFC and PS increases at P_v's ≥ 55 mmHg were quantitatively similar to those induced by histamine-type mediators in the same preparation. It is concluded that capillary hydraulic conductivity can increase markedly but reversibly upon large P_v elevations, and that this is mainly due to forceful opening of ordinarily closed ‘large pores’ in the microvascular membrane, rather than being caused by lesional rifts in the endothelium,     

Pattern of fluid accumulation in NO2-induced pulmonary edema in dogs. A morphometric study.

To ascertain whether the pattern of fluid accumulation could be altered by an agent introduced through the airways, the authors studied the physiology and morphology of 11 dogs exposed to 150-494 ppm.hr NO2 and compared them with 3 new and 5 previously reported control dogs. NO2 caused a partly reversible decrease in systemic arterial pressure and cardiac output, a fall in arterial PO2, and rapid shallow breathing, while pulmonary arterial and wedge pressures remained normal. Post mortem, lower (LL) and middle (ML) lobes were frozen, sections fixed for light microscopy by freeze-substitution, and wet weight/dry weight (W/D) ratios were measured. Alveolar edema was graded, and the distribution of interstitial edema around arteries and veins and within bronchovascular bundles was studied with morphometry: edema ratios (ER) were calculated as area of interstitium/area of vessel or airway. We found that NO2 produced an exposure-dependent increase in lung water (r = 0.73), and that both LL and ML had similar W/D ratios (7.77 and 8.39, respectively) and percent alveolar edema (30% and 34%). Morphometry of interstitial edema showed that the ER for vessels and airways of edematous LL were essentially similar to controls, while those of the ML were markedly increased. It is concluded that NO2 produces exposure-related lung edema and preferential alveolar flooding with probable secondary interstitial accumulation. The discrepancies in interstitial edema between middle and lower lobes may be due to differences in lung volume or in ventilation.     

An ultrastructural morphometric comparison of the right and left sides and lobes of the dog lung

Regional variations of the components of lobes of the lung have been recognized to result from gravitational effects. Excised and isolated perfused lungs are frequently used as objects for studies of fluid flow. This ultrastructural study considered differences between the right and left sides and lobes of the excised lung. The lungs of three mongrel dogs were fixed by simultaneous endotracheal instillation of glutaraldehyde and immersion in fixative. Stratified random sampling, point-counting volumetry, and line intercept counts were utilized to determine the volume densities of alveolar space, endothelial vesicles, interstitial cells, fibers, and matrix. Thicknesses of the air-blood barrier, epithelial, interstitial, and endothelial compartments were measured. Values for the right side were compared to values for the left by t-test. Values for lobes were compared statistically by a two-way analysis of variance. There was no statistically significant column effect, no row effect, and no interaction between the mean measurements of the factors computed for the right and left lungs and the lobes within the lungs. It is concluded that stratified random sampling combined with endotracheal and immersion fixation as used in this study equalize regional differences in the alveolar lumen volume and air-blood barrier thickness. With these conditions there are no significant differences by sides or lobes in the volume densities of the epithelial and endothelial cells and components of the interstitium of the air-blood barrier.     

Model of interstitial pressure as a result of cyclical changes in the capillary wall fluid transport.

Reported interstitial pressures range from -8 to +6 mm Hg in different tissues and from <-20 mm Hg in burned tissue or more than +30 mm Hg in tumors. We have tried to link interstitial pressure to the here proposed cyclical changes in the fluid transport across the capillary wall.In the presented model interstitial pressure is considered as an average of pressures in numerous pericapillary spaces. A single pericapillary pressure is a dynamic difference between the net outward (hydraulic pressure+interstitial colloid osmotic pressure) and inward (plasma colloid oncotic pressure) forces. Hence, dominating net outward forces would result in a positive pericapillary interstitial pressure, while stronger inward forces would produce negative pressures in the pericapillary space. All interruptions of blood flow leave some blood in capillaries with a normal oncotic pressure and no hydrostatic pressure that might act as a strong absorber of interstitial fluid until the blood flow is reestablished.Model assumptions for the systemic circulation capillaries include (a) precapillary sphincters can almost entirely stop the capillary flow, (b) only a minority of sphincters are normally open in the tissue, and (c) hydrostatic pressures in unperfused capillaries are similar to the pressures at their venous ends.The key proposal is that capillaries with closed precapillary sphincters along their entire length have low hydrostatic pressure of 10 to 15 mm Hg. This pressure cannot force filtration, so these capillaries reabsorb interstitial fluid from the pericapillary space along their entire length. In the open capillaries, hydrostatic pressure filtrates fluid to the pericapillary space along most of their length. Fluid enters, moves some 20 or 30 micrometers away and back to be reabsorbed at the same point. Closed periods are periods of intense fluid reabsorption, while the short open periods refill the space with fresh fluid. It can be calculated that subcutaneous tissue interstitial pressure values might develop if the closed periods are 1.14 to 2.66 times longer than the open periods. Positive interstitial pressures observed in some organs might develop if open periods are longer than the closed periods.High interstitial colloid pressure in lungs makes both perfused and unperfused capillaries absorptive, resulting in more negative values of lung interstitial pressure. The same model is used to explain interstitial pressure values in tumors, burned tissue and intestinal villi.     

Analysis of regional mechanics in canine lung injury using forced oscillations and 3D image registration

Acute lung injury is characterized by heterogeneity of regional mechanical properties, which is thought to be correlated with disease severity. The feasibility of using respiratory input impedance (Z _rs) and computed tomographic (CT) image registration for assessing parenchymal mechanical heterogeneity was evaluated. In six dogs, measurements of Z _rs before and after oleic acid injury at various distending pressures were obtained, followed by whole lung CT scans. Each Z _rs spectrum was fit with a model incorporating variable distributions of regional compliances. CT image pairs at different inflation pressures were matched using an image registration algorithm, from which distributions of regional compliances from the resulting anatomic deformation fields were computed. Under baseline conditions, average model compliance decreased with increasing inflation pressure, reflecting parenchymal stiffening. After lung injury, these average compliances decreased at each pressure, indicating derecruitment, alveolar flooding, or alterations in intrinsic tissue elastance. However, average compliance did not change as inflation pressure increased, consistent with simultaneous recruitment and strain stiffening. Image registration revealed peaked distributions of regional compliances, and that small portions of the lung might undergo relative compression during inflation. The authors conclude that assessments of lung function using Z _rs combined with the structural alterations inferred from image registration provide unique but complementary information on the mechanical derangements associated with lung injury.     

Analysis of the pressure-flow characteristics of isolated perfused rat kidneys with inhibited tubular reabsorption

The renal hemodynamics were studied in an isolated perfused rat kidney model modified for investigations of the glomerular permeability characteristics. The tubular reabsorptive activity was inhibited by perfusion at low temperature (8 ^oC) in the presence of furosemide and nitroprusside resulting in a dramatic increase in the filtered load of fluid and solute reaching the tubules and hence in tubular pressure. The glomerular filtration rate (GFR), arterial pressure (P_A) aid needle pressure (intrarenal tissue pressure, P_iR) were continuously recorded and the glomerular hydrostatic pressure was estimated by an arterial occlusion technique. The pre- to postglomerular resistance ratio was calculated from the pressure vs. GFR relationships for two perfusates having differing oncotic pressures (π= 5.5 and 77 = 20 mmHg), from which estimations of glomerular hydrostatic pressures (P_GC) were concomitantly made. Thus, increases in An could be exactly counterbalanced by equally large increases in P_ac for any given GFR, the needle and Bowman's capsule pressures being dependent on GFR but not on plasma colloid oncotic pressure. The experimental interventions resulted in a pronounced elevation of P_iR as compared with in vivo conditions, while the P_GC values were in a normal range, resulting in reduced glomerular filtration pressures. Furthermore, the clearance of albumin varied with the oncotic pressure in agreement with the notion of heteroporosity.     

Pulmonary ischemia/reperfusion injury: A quantitative study of structure and function in isolated heart‐lungs of the rat

Early graft dysfunction after lung transplantation is a significant and unpredictable problem. Our study aimed at a detailed investigation of structure‐function correlations in a rat isolated heart‐lung model of ischemia/reperfusion injury. Variable degrees of injury were induced by preservation with potassium‐modified Euro‐Collins solutions, 2 hr of cold ischemia, and 40 min of reperfusion. Pulmonary artery pressure (P_pa), pulmonary vascular resistance (PVR), peak inspiratory pressure (PIP), and perfusate gases (ΔP_O2, ΔP_CO2) were recorded during reperfusion. Right lungs were used to calculate W/D‐weight ratios. Nineteen experimental and six control left lungs were fixed for light and electron microscopy by vascular perfusion. Systematic random samples were analyzed by stereology to determine absolute and relative volumes of lung structures, the amount of interstitial and intraalveolar edema, and the extent of epithelial injury. Lectin‐ and immunohistochemistry using established epithelial cell markers were performed in three animals per group to reveal sites of severe focal damage. Experimental lungs showed a wide range in severity of ischemia/reperfusion injury. Intraalveolar edema fluid amounted to 77–909 mm³ with a mean of 448±250 mm³ as compared with 22±22 mm³ in control lungs (P<0.001). Perfusate oxygenation (ΔP_O2) decreased from 30.5±15.2 to 21.7±15.2 mm Hg (P=0.05) recorded after 5 and 40 minutes of reperfusion. In experimental lungs, a surface fraction of 1% to 58% of total type I pneumocyte surface was damaged. Intraalveolar edema per gas exchange region (Vv ape,P) and ΔP_O2 were related according to ΔP_O2 = 96 − 60 × log₁₀(Vv ape,P) [mm Hg]. The extent of epithelial injury did not correlate with ΔP_O2 nor with intraalveolar edema, but increased significantly with PVR. Lectin‐ and immunohistochemistry revealed focal severe damage to the alveolar epithelium at the border of perivascular cuffs. We conclude that ischemia/reperfusion‐associated respiratory compromise is a direct function of the amount of intraalveolar edema, however, it is not determined by the actual extent of diffuse alveolar epithelial damage at the air‐blood‐barrier but by the presence of focal severe epithelial damage at the perivascular/alveolar interface. Anat Rec 255:84–99, 1999. © 1999 Wiley‐Liss, Inc.     

Differentiation of Vasoconstrictor Sensitivity Caused by Prostaglandin E in Peripheral Vascular Beds of the Rabbit

The increase in perfusion pressure in the rabbit ear, hindleg and mesentery caused by close intra-arterial injection of noradrenaline (NA), and the contractile response to NA of the rabbit aortic strip were investigated with respect to their sensitivity to prostaglandin E₁ (PGE₁) and to the prostaglandin synthesis inhibitor indomethacin. PGEj (100–200 ng) potentiated the increases in perfusion pressure caused by NA in the perfused hindleg and mesentery, and the contractile response to NA of the aortic strip by 25–80%, but inhibited the increase in perfusion pressure by NA in the perfused ear by 35–100%. Indomethacin (3–5 10^-5 M) significantly decreased the pressor responses to NA in the hindleg (by 45%) and mesentery (by 55%). This inhibitory effect by indomethacin was completely reversed by PGE₁. The responses to NA in the aortic strip and the perfused ear were unaffected by indomethacin. It is concluded that the process of vasoconstriction in the vascular beds of the rabbit displays qualitative differences concerning its sensitivity to added PGEj. Furthermore, the decreased pressor responses to NA observed in some of the rabbit vascular beds after indomethacin indicate that the sensitivity to NA in these tissues in fact is increased by endogenous prostaglandin-like substances (PLS). The current results thus suggest that endogenous PLS may regulate, at a local level, the vasoconstrictor sensitivity in the rabbit systemic resistance vessels.     

Effect of alveolar hypoxia on segmental pulmonary vascular resistance and lung fluid balance in dogs

In a biventricular bypass preparation with constant-flow perfusion, pulmonary arterial pressure (P_pa), average pulmonary capillary pressure (P_pc), venous pressure (P_v), extravascular lung water volume (EVW_d) and capillary permeability-surface area product for urea (PS) were determined in control animals and in animals subjected to alveolar hypoxia. During hypoxia, P_pa increased in a biphasic manner, the site of hypoxic pulmonary vasoconstriction being located in the arterial upstream segment. At baseline, P_pc values were identical in control and experimental animals (3.4 ± 0.4 vs. 3.6 ± 0.2 mmHg). During 150 min of airway hypoxia, the rise in P_pc (5.1 ± 0.3mmHg) did not exceed the rise in P_pc (4.9 ± 0.5mmHg) recorded in control animals at same time interval during normoxic ventilation. EVW_d increased during hypoxia to values significantly higher than those obtained in control animals (0.559 ± 0.036 vs. 0.466 ± 0.027 mL water g^?1 lung). PS remained unchanged at baseline level throughout experiments in both groups of animals. Present data suggest that lung oedema formation during alveolar hypoxia may be caused by increased transcapillary fluid loss preferentially through transcellular hydraulic pathways in capillary endothelial cells.     

The relationship between interstitial fluid pressure and volume in rat trachea

A change of interstitial fluid volume (IFV) will normally change the interstitial fluid pressure (P_if) so as to counteract further fluid movement across the capillaries and changes in IFV. Contrary to this, several acute inflammatory reactions in the trachea are associated with increased negativity of P_if, which will interstitial fluid balance in the trachea, interstitial compliance (ΔIFV/ΔP_if) was measured in pentobarbital anaesthetized rats. IFV was measured as the plasma equivalent extravascular distribution space of [⁵¹Cr]EDTA. P_if was measured in the same animal with sharpened glass pipettes (diameter 3–6 μm) connected to a servocontrolled counterpressure system. In dehydration (30 mL saline i.v., n=10) interstitial compliance was 0.083 mL g dry wt^-1 mmHg^-1. Since control IFV was 1.046 mL g dry wt^-1 (n=10) the interstitial compliance is 8% of IFV per mmHg. In overhydration (30 mL NaCl, n=10) and dextran anaphylaxis (1 mL dextran 70, n=10) compliance remained the same for the first 15% increase in IFV and then increased several-fold since P_if did not increase more than 2 mmHg above control level. The increased negativity of P_if by -10 mmHg associated with acute inflammation will require a reduction of IFV by 80% when interstitial compliance is 8% per mmHg. A more likely explanation is therefore that structural rearrangements are responsible for the events leading to increased negativity of P_if in acute inflammation.     

Mechanics of lung fluid balance

Recent research in pulmonary physiology, anatomy, and mechanics have clarified our general understanding of liquid and solute transport through the lung. Fluid crosses the microvascular endothelial membrane at a rate that depends on gradients in the transmembrane hydrostatic and osmotic pressures and the conductance of the permeable membrane. Under normal conditions, the filtered fluid is removed by an efficient lymphatic pump. Edema accumulates in the lung when an increased flux due to an elevated vascular pressure or to a more permeable membrane is not matched by an adequate lymph clearance rate. Initially a favorable hydrostatic pressure gradient drives the excess fluid into interstitial spaces surrounding large blood vessels and airways away from filtration sites near capillaries and thereby ensures efficient gas exchange. Further edema formation reduces the pressure gradient, eventually leading to the flooding of alveolar air spaces and impaired gas exchange. I will focus on the role of the above forces in the regulation of extravascular lung water. It will become clear that many details of the general scheme are not known, and our conceptual understanding of the relevant mechanisms involved is often rudimentary and incomplete. Some of the more important questions pertain to the interstitial pressure around capillaries, the resistance and compliance of the interstitial matrix, and the role of the lymphatics in regulating interstitial fluid volume and interstitial pressure.     

The effect of 2 hours of complete unilateral ureteral obstruction on tubuloglomerular feedback control

The mechanisms affecting renal blood flow and filtration during and after unilateral ureteral obstruction (UUO) are incompletely understood. Since ureteral obstruction leads to changes in interstitial pressure and volume, and since we have previously shown that interstitial pressure conditions can modulate the sensitivity of the tubuloglomerular feedback (TGF) control system, we sought in the present study to define the contribution of the TGF system to changes in GFR during and after UUO, and to observe associated changes in pressures in vessels, tubules and the interstitial space. Interstitial pressures and glomerular filtration rate (GFR) were measured in one group of Sprague Dawley rats. Interstitial hydraulic pressure was determined with a thin catheter placed in the subcapsular space. Interstitial oncotic pressure was estimated from the protein concentration in collected hilar lymph. In a second group of rats proximal tubule pressure (PT) and stop-flow pressure (PSF) were measured during the first three hours of UUO and after 24 h UUO. In a third group of rats PSF was measured while the loop of Henle was perfused at different rates. The sensitivity of the TGF system was determined from the maximal drop in stop-flow pressure (delta PSF) and the turning point (TP)--the tubule perfusion rate at which 50% of this maximal stop-flow pressure response was obtained. In a fourth group of rats proximal tubule flow-rate was measured after release of 2 hrs UUO. The results show that PT and PSF are both increased during the first three hours of obstruction and that they return to normal or sub-normal levels after 24 h of UUO.(ABSTRACT TRUNCATED AT 250 WORDS)