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C R Robertson

Publications and source records attributed to C R Robertson.

At least 37 records · Page 2Linked to original sources

The medullary microcirculation.

Like other regional circulations, the medullary circulation supplies oxygen and other primary substrates to the medulla and removes carbon dioxide and other waste metabolites. It also acts as a countercurrent exchanger and simultaneously removes water reabsorbed from the renal tubule to preserve mass balance. Our present understanding of how the medulla serves both these functions at the same time is illustrated in Figure 3. Blood leaves the efferent arteriole with an elevated plasma protein concentration as a consequence of glomerular filtration, and flows down descending vasa recta within a vascular bundle. The increased interstitial osmotic-concentration coupled with a finite capillary reflection coefficient for small solutes causes additional water to be extracted so that at the termination of descending vasa recta, the plasma protein concentration exceeds that in the systemic circulation by approximately twofold. Solute, urea more than sodium chloride, also enters descending vasa recta. As blood flows through the interconnecting capillary plexus and up ascending vasa recta, transcapillary oncotic and osmotic pressure differences combine to cause capillary uptake of fluid. There is also simultaneous loss of urea such that the medullary trapping of urea is very effective. Countercurrent exchange of sodium chloride, however, appears to be less efficient and as a consequence, not only water but sodium chloride is removed from the medulla. Antidiuretic hormone reduces medullary blood flow, both directly by its vasoconstrictor (V1-receptor mediated) effect and indirectly by its antidiuretic (V2-receptor mediated) effects. Prostaglandins are able to enhance medullary blood flow by counteracting vasoconstrictive influences.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of atrial natriuretic peptide on vasa recta blood flow in the rat.

To determine whether synthetic atrial natriuretic peptide (ANP) increases renal medullary blood flow and if so whether the increase mediates the diuresis and natriuresis induced by ANP, inner medullary vasa recta blood flow in the exposed left renal papilla of anesthetized Munich Wistar rats weighing between 102 and 161 g was measured by fluorescence videomicroscopy. The rats were maintained in a euvolemic state by the infusion of albumin. Synthetic ANP (Auriculin B) was administered intravenously as 2.5 micrograms/kg body wt prime and as a continuous infusion of 0.2 microgram X min-1 X kg body wt-1 to the experimental group (n = 7). Within 2 min after ANP was given, urine flow and sodium excretion increased (29.4 +/- 3.8 to 50.4 +/- 5.8 microliter X min-1 X kidney wt-1, P less than 0.01, and 3.39 +/- 0.57 to 6.05 +/- 0.95 mueq X min-1 X g kidney wt-1, P less than 0.01, respectively), but vasa recta blood flow in descending (DVR) or ascending (AVR) vasa recta did not change significantly (9.5 +/- 2.3 to 10.0 +/- 2.8 nl/min in DVR and 5.3 +/- 1.0 to 6.1 +/- 1.2 nl/min in AVR). Forty-five minutes after ANP was begun, urine flow and sodium excretion increased further (77.1 +/- 11.1 microliter X min-1 X g kidney wt-1 and 12.0 +/- 2.15 mueq X min-1 X g kidney wt-1, respectively), and by this time vasa recta blood flow had increased significantly to 14.0 +/- 2.6 in DVR, P less than 0.01, and 9.8 +/- 1.2 in AVR, P less than 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of V2-receptor-mediated changes on inner medullary blood flow induced by AVP.

We have previously shown that arginine vasopressin (AVP) in physiological amounts reduces inner medullary blood flow and that the mechanism of this decrease is at least in part mediated by the vasopressor (V1-receptor) action of AVP. To determine whether the antidiuretic action of AVP (V2-receptor) also contributes to the reduction in inner medullary blood flow, we determined capillary blood flow (QVR) in individual descending vasa recta (DVR) and ascending vasa recta (AVR) using fluorescence videomicroscopy in the exposed renal papilla of the anesthetized rat. Three groups of chronically water-diuretic rats were studied in three consecutive periods: control (period 1), experimental (period 2), and recovery (period 3). Group I rats (designated the AVP group) received AVP, 45 ng X h-1 X kg body wt-1; group II (AVP + V2-inhibitor), AVP plus its specific antidiuretic antagonist d(CH2)5[D-Ile2,Thr4]AVP; and group III (V2-inhibitor), the antagonist alone, respectively, in the experimental period 2. Only group I rats concentrated their urine, urine osmolality (Uosmol) = 499 +/- 48 mosmol/kgH2O, whereas urine remained hypotonic throughout in groups II and III. In group I, QVR in DVR and AVR decreased in period 2; but in groups II and III, QVR tended to increase. These results suggest that the AVP-induced decrease in papillary vasa recta blood flow is in part mediated by its antidiuretic V2-receptor as well as by its vasopressor (V1-receptor). They also suggest that the rate of urinary flow in the medullary collecting ducts is a determinant of inner medullary blood flow.

Aminohippuric Acids↗

Videomicroscopic method for direct determination of blood flow to the papilla of the kidney.

We adapted the technique of videomicroscopy for direct determination of blood flow in individual capillaries of the papilla of the kidney, the ascending vasa recta (AVR) and descending vasa recta (DVR). The papilla was exposed in anesthetized rats and positioned under a video-camera-microscope and viewed under epiillumination. The intravenous infusion of fluorescein-isothiocyanate (FITC)-labeled gamma globulin was combined with fluorescence microscopy to enhance the contrast among plasma, red blood cells and capillary walls. On the television monitor, the walls were clearly outlined, enabling the measurement of capillary diameter. The velocity of red cells (Vrbc) in individual vasa recta was measured using the dual slit technique. From the videotape recorded microscopic image of a vas rectum, two photometric signals were obtained by integrating the light intensity from two electronic "windows" positioned closely together over the same capillary. Red cell velocity was calculated by dividing the distance between the two windows by the time delay between signals. The delay was determined using analog correlation tracking or digital cross correlation techniques. Single vasa recta blood flow was calculated from capillary diameter, Vrbc, and F (Fahraeus factor), which converts Vrbc to average whole blood velocity, Vblood. In quartz capillaries the same size as vasa recta, the ratio F = Vrbc/Vblood = 1.42 +/- 0.06. Total papillary blood inflow and outflow was calculated by multiplying the total number of DVR or AVR times the mean single capillary blood flow for DVR or AVR, respectively.

Animals↗

Use of digital cross-correlation for on-line determination of single-vessel blood flow in the mammalian kidney.

The empirical relationship between erythrocyte velocity (Vrbc) and mean blood velocity (Vblood) was studied in quartz capillaries by television microscopy using the dual-slit technique. A newly designed desktop digital on-line cross-correlator was combined with a computer to determine Vrbc. The accuracy of the digital correlator was tested for velocities ranging from 0 to 3 mm/sec and compared with values determined using an analog tracking correlation device. There was good agreement. Small-bore glass tubes with diameters ranging from 12 to 26 micron were perfused with suspensions of erythrocytes having hematocrits between 10 and 37%. The relationship between mean blood velocity and erythrocyte velocity in these quartz tubes was found to be Vblood = 0.88 Vrbc - 0.11, and was independent of diameter and hematocrit within the range investigated. The mean ratio for Vrbc/Vblood was 1.42 +/- 0.06.

Capillaries↗

Fluid uptake in the renal papilla by vasa recta estimated by two methods simultaneously.

Fluid uptake by vasa recta was determined by two independent methods, videomicroscopy and the micropuncture technique, in the exposed papilla of nine antidiuretic rats to reconcile differences in values previously obtained by the two techniques. Erythrocyte velocity (Vrbc) and diameter (D) in descending vasa recta (DVR) (n = 22) and ascending vasa recta (AVR) (n = 31) near the "base" of the papilla were measured. Using a conversion function determined in vitro, Vrbc was transformed into mean blood velocity (Vblood). From D and Vblood, mean blood flow (Q) in DVR and AVR was calculated. In DVR, mean Vrbc, D, and Q were 1.06 +/- 0.01 mm/s, 16.3 +/- 0.4 micron, and 10.6 +/- 1.4 nl/min, respectively. In AVR, each corresponding value differed significantly, 0.47 +/- 0.06 mm/s (P less than 0.001), 19.8 +/- 0.8 micron (P less than 0.001), and 5.65 +/- 1.3 nl/min (P less than 0.025), respectively. Blood samples from DVR and AVR were obtained by micropuncture from the same location. Plasma protein concentration (g/dl) was 5.1 +/- 0.6 in DVR, 4.0 +/- 0.4 (P less than 0.05) in AVR, and 3.6 +/- 0.3 (P less than 0.025) in the renal vein. Assuming no net transcapillary loss of protein, total plasma outflow exceeded inflow by 29%, the excess representing fluid uptake; and to reconcile the blood flow and plasma protein concentrations found, functioning AVR should outnumber functioning DVR by a ratio of 2.1-2.4 to 1, depending on local hematocrit. Given the total number of AVR + DVR = 2,944 (at the base), capillary fluid uptake was calculated to range between 1.5 and 2.6 microliter/min.

Animals↗

Effect of arginine vasopressin on renal medullary blood flow. A videomicroscopic study in the rat.

The role of arginine vasopressin (AVP) in the regulation of renal medullary blood flow is uncertain. To determine if AVP has a direct vasoconstrictive action on vasa recta, the effect of AVP on erythrocyte velocity (VRBC), diameter, and blood flow (QVR) in descending vasa recta (DVR) and ascending vasa recta (AVR) was studied in the exposed renal papilla of four groups of chronically water diuretic rats using fluorescence videomicroscopy. There were three periods: control (period 1), experimental (period 2), and recovery (period 3). In periods 1 and 3, all groups received hypotonic saline. In period 2, group I rats (AVP) received AVP (45 ng/h per kg body wt); group II (time) received hypotonic saline alone; group III (AVP plus V1-inhibitor) received AVP plus its vascular antagonist, d(CH2)5Tyr(Me)AVP; and group IV (V1-inhibitor) received the vascular antagonist alone. Another group of rats (group V) was employed to demonstrate that the rise in blood pressure induced by a 3- or 10-ng/kg injection of AVP was virtually abolished by the prior infusion of the V1-inhibitor. The urine of group III as well as group I rats was concentrated (Uosm = 721 +/- 62 H2O vs. 670 +/- 39 mosM/kg), while urine remained dilute in groups II and IV. In period 2, VRBC and QVR in DVR and AVR decreased in group I, did not decrease in group III, and increased in groups II and IV. The vascular antagonist thus completely abolished the AVP-induced decrease in QVR in group III. These findings unequivocally establish that AVP in physiological amounts reduces medullary blood flow, at least in part, by a direct vasoconstrictive action on the medullary microcirculation. They also show that an effect of AVP on medullary blood flow is not necessary for its antidiuretic effect.

Animals↗

Prostaglandin synthesis inhibitors and vasa recta erythrocyte velocities in the rat.

Vasa recta erythrocyte velocities (VRBC) in the exposed renal papilla of anesthetized water-loaded rats were determined before and 60 min after intravenous administration of a prostaglandin synthesis inhibitor (indomethacin, meclofenamate) or the inhibitor vehicle alone. The change in VRBC of ascending and descending vasa recta for the inhibitor group [-17 +/- 5% (SE)] was different from that for controls (+12 +/- 4%, P less than 0.002). Erythrocyte velocities were also determined in vasa recta of antidiuretic rats before and 30 min after administration of indomethacin or vehicle alone. Prostaglandin synthesis inhibition was again associated with a significant decrease in VRBC compared with control (-24 +/- 4% vs. +28 +/- 20%, respectively, P less than 0.025). These findings suggest that prostaglandins play a similar role in regulating blood flow in the renal medulla in water diuresis and antidiuresis.

Animals↗

Nature of the renal injury following total renal ischemia in man.

The effects of total renal ischemia (TRI) of 15-87 min duration due to suprarenal clamping of the aorta were studied in 15 mannitol-treated patients undergoing abdominal aortic surgery. 15 patients undergoing similar surgery but requiring only infrarenal clamping served as controls. 1-2 h following TRI, GFR was reduced to only 39% of that in controls, 23 +/- 5 vs. 59 +/- 7 ml/min (P less than 0.001). This could not be ascribed to impaired renal plasma flow (RPF), which was mildly reduced to 331 +/- 71 and was not different from the value in controls, 407 +/- 66 ml/min. However, impaired PAH extraction (43 +/- 7%) and isosthenuria, not present in controls, suggest a primary role for tubular injury in lowering GFR at this time. 24 h following TRI, the GFR remained depressed below controls, 45 +/- 8 vs. 84 +/- 8 ml/min (P less than 0.005), while the transglomerular sieving of neutral dextrans was significantly enhanced (radius interval, 24-40 A). A theoretical analysis of transcapillary solute exchange revealed that these findings could be largely explained by a selective reduction of either RPF (-61%) or of transmembrane hydraulic pressure difference (-18%) below control values. Alternately, a combination of these two factors with changes of smaller magnitude could explain the findings. In contrast, a selective increase in oncotic pressure or decrease of the glomerular ultrafiltration coefficient could be excluded as a cause of hypofiltration 24 h after TRI. These observations lead us to suggest that the transient azotemia observed following TRI is due to a self-limited injury to the nephron that is identical to that seen in overt and sustained forms of acute renal failure.

Aged↗

Ethanol Production by Saccharomyces cerevisiae Immobilized in Hollow-Fiber Membrane Bioreactors.

Saccharomyces cerevisiae ATCC 4126 was grown within the macroporous matrix of asymmetric-walled polysulfone hollow-fiber membranes and on the exterior surfaces of isotropic-walled polypropylene hollow-fiber membranes. Nutrients were supplied and products were removed by single-pass perfusion of the fiber lumens. Growth of yeast cells within the macrovoids of the asymmetric-walled membranes attained densities of greater than 10 cells per ml and in some regions accounted for nearly 100% of the available macrovoid volume, forming a tissue-like mass. A radial distribution of cell packing existed across the fiber wall, indicating an inadequate glucose supply to cells located beyond 100 mum from the lumen surface. By comparison, yeast cell growth on the exterior surfaces of the isotropic-walled membranes resulted in an average density of 3.5 x 10 viable cells per ml. Ethanol production by reactors containing isotropic polypropylene fibers reached a maximum value of 26 g/liter-h based on the total reactor volume. Reactor performance depended on the fiber packing density and on the glucose medium flow rate and was limited by low nutrient and product transport rates. The inhibition of ethanol production and the reduction in fermentation efficiency arose primarily from the accumulation of CO(2) gas within the sealed reactor shell space.

Journal Article↗

Direct determination of vasa recta blood flow in the rat renal papilla.

Blood flow in vasa recta capillaries of the exposed renal papilla of young antidiuretic rats (n = 18) was determined by an adaptation of the video-photometric technique of Intaglietta. The erythrocyte velocity and capillary diameter in vasa recta (n = 97) were measured at the same location by means of fluorescence video microscopy, with fluorescein-labeled bovine gamma-globulin as a plasma marker. A factor relating erythrocyte velocity to mean cross-sectional blood velocity was determined in vitro to permit the calculation of single vasa recta blood flows from the measured indices, erythrocyte velocity and capillary diameter. Mean blood flow in descending vasa recta was 8.83 +/- 0.96 (SE) nl/min, significantly greater than that in ascending vasa recta, 4.82 +/- 0.34 nl/min. The total numbers of ascending and descending vasa recta at the base of the exposed papilla were also determined. Over 1500 vasa recta were identified as ascending vasa recta or descending vasa recta in electron micrographs of three papillas. At this level in the papilla (2 mm from the tip), there were four ascending vasa recta for each descending vas rectum. From the total numbers of ascending vasa recta and descending vas rectum, single vessel blood flows were converted to total blood flow. Total blood outflow in all ascending vasa recta, 11.3 microliter/min, substantially exceeded total blood inflow in all descending vasa recta, 5.2 microliter/min. The difference between outflow and inflow (6.1 microliter/min) represents an estimate of water by the papillary microcirculation, and is more than adequate to accommodate the known rate of water reabsorption from the collecting ducts of the exposed papilla.

Animals↗

The nature of the glomerular injury in minimal change and focal sclerosing glomerulopathies.

Glomerular barrier function was evaluated in 12 healthy human volunteers and in 16 proteinuric patients in whom the nephrotic syndrome was associated with alteration of glomerular epithelial cells alone (minimal change nephropathy [MCN]) or in combination with focal glomerular sclerosis (FGS). We determined the glomerular sieving coefficient for each of nine narrow dextran fractions (Einstein Stoke radius [ESR] = 30 to 46 A), and directly measured, or indirectly estimated, values for the determinants of glomerular ultrafiltration. These quantities were then subjected to analysis based on an hydrodynamic theory of solute transport through an isoporous membrane. The results indicate that relative to normal subjects, effective pore radius is reduced from 59 to 55 and 53 A in McN and FGS, respectively; while the ratio, pore area to pore length (a measure of pore density) is correspondingly reduced from 21.7 X 10(6) to 10.1 X 10(6) and 4.7 X 10(6) cm. respectively, We suggest that collapse of the anionic glomerular membrane matrix in these proteinuric disorders may lead to pore shrinkage and reduced pore density, but that reduced electrostatic repulsion of anionic albumin (ESR = 36 A) facilitates its permeation into Bowman's space. The qualitatively similar disorder of glomerular barrier function in MCN and FGS is consistent with a unitary pathogenesis, but may represent a nonspecific response to depletion of glomerular polyanion.

Adolescent↗