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D J Marsh

Publications and source records attributed to D J Marsh.

At least 163 records · Page 9Linked to original sources
PubMed1980

Loop of Henle during the water-to-antidiuresis transition in Brattleboro rats.

A mathematical model of the renal medulla predicted patterns of NaCl and urea concentration and flow rate when a rat undergoing water diuresis receives antidiuretic hormone (ADH), We tested these predictions with micropuncture and clearance experiments in Brattleboro rats lacking endogenous ADH. The model successfully predicted urine flow rate, urea excretion rate, and ascending vasa recta (AVR) solute concentration patterns. A novel result the model correctly foresaw was that AVR urea concentration lagged behind NaCl, because ADH temporarily interrupted urea recycling. The model suggested that this lag would be carried over to descending limb of Henle's loop (DLH) fluid only if DLH permeabilities allowed solutes as well as water to move across the DLH wall, but not if solute movement was negligible. Experimental results showed the lag, therby suggesting significant solute entry into DLH fluid during the transition, and, by extension, in other conditions as well, As shown in a companion paper (Am. J. Physiol. 239 (Renal Fluid Electrolyte Physiol. 8): F57-F71, 1980), solute permeation across DLH limits hypertonic urine formation in the inner medulla unless thin ascending limbs perform active transport of NaCl.

Animals↗
PubMed1979

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.

Animals↗
PubMed1978

Optical spectroscopic study of the ADP-myosin interaction.

The binding of ADP to heavy meromyosin, and the separated subfragment 1 components S-1(A1) and S-1 (A2), has been observed by ultraviolet spectrophotometry. The results are compatible with the presence of spectroscopically equivalent and independent sites, one per head, at both 10 degrees C and 25 degrees C. We do not observe the heterogeneity of binding and of the spectroscopic response that has been reported. The binding has also been followed by other methods sensitive to the effect of ligand on the aromatic residues of the protein, viz. intrinsic fluorescence of heavy meromyosin and changes in the near-ultraviolet Cotton effects of myosin, and its active fragments. Within the limits of our experimental precision, the binding profiles, based on concentration of myosin heads, are the same for myosin as for subfragment 1. A perturbation in the circular dichroism is also generated by pyrophosphate, which competes with ADP. The spectra suggest that subsites for the purine ring and the diphosphate can be recognized. The sensitivity of binding profiles obtained by methods of the kind used here to cooperative or antagonistic interactions between the binding sites has been analysed. It is clear that sizeable effects of this nature could be concealed by the binding curves, even for high experimental precision.

Adenosine Diphosphate↗
PubMed1977

An investigation of heavy meromyosin-ADP binding equilibria by proton release measurements.

The interaction of magnesium-ADP with skeletal muscle heavy meromyosin has been studied by measuring the accompanying release of protons. Total pH changes of the order of 0.03 were involved, and measurements were performed with a discrimination of some ten-thousandths of a pH unit. At pH 8.0 and 25 degrees C about 0.5 mol of protons per mol of heavy meromyosin is released at saturation. A stoichiometry of binding close to 2 mol of ADP per mol of protein was found, with a binding constant, obtained from the proton release titration curve (pH 8.0, 25 degrees C), of 2 X 10(5) M-1. At 5 degrees C the release of protons per mole is slightly greater, and the binding constant is somewhat increased, reflecting a negative enthalpy of binding. Similar proton release behavior is observed in the presence of manganous ions in place of magnesium. The liberation of protons is thus unrelated to the temperature-dependent isomerization of myosin in the presence of substrate. Alkylation of a reactive thiol group (SH1) does not change the proton liberation at pH 8.0. From the pH dependence of proton release, the association constant of heavy meromyosin with magnesium-ADP at other pH values can be inferred and shows an appreciable rise as the pH increases. The pH-proton release profile also allows the pK of the ionizing groups perturbed by the ligand to be deduced. At least two groups ionizing above pH 7 and one below are involved. Their pK's in the unperturbed state are assigned as 8.5, 9.3, and about 6.6, respectively; they are displaced in the complex to about 8.0, 9.1, and 6.3. A relation to the pH-activity profile of myosin ATPase is indicated. The pH-proton release profile is somewhat changed when the SH1 group is alkylated. Measurements with potassium-ADP, in the absence of magnesium, show that at pH 8.0 there is no proton release but rather a sizeable proton absorption (about 0.5 mol of protons per mol of heavy meromyosin). The association constant derived from the titration curves (pH 8.0, 25 degrees C) is 3 X 10(4) M-1.

Adenosine Diphosphate↗
PubMed1977

Patterns of plasma free fatty acid concentrations in fasted, resting dogs.

Free fatty acid (FFA) concentrations were determined in arterial plasma samples obtained during short or prolonged fasts from resting, conscious adult male mongrel dogs. Arterial blood was continuously collected during experiments ranging from 2.25 to 15 h, from dogs fasted 1 or 5 days. Each continuous collection stream was divided at 45 equal intervals into separate sequential samples. In 18 experiments, no consistent pattern was found in plasma FFA concentrations: the concentrations were never constant, and fluctuations were only rarely periodic. Large, spontaneous, seemingly random level changes with amplitudes of 200-600 mueq/liter were observed in 14 experiments, that took from 1 to 8 h to complete. There was no apparent relation between these fluctuations and time of day or rectal temperature, and glucose concentrations remained unchanged during the FFA fluctuations. The inconstancy of plasma FFA levels and the irregularity of their fluctuations suggests that FFA production rates may be unregulated or only loosely regulated within a wide regulation band during the first few days of starvation. No current model of FFA metabolism preducts the observed patterns of FFA levels.

Animals↗
PubMed1977

Origin of electrical PD's in hamster thin ascending limbs of Henle's loop.

Microelectrodes with 2-micronm-tip diameters arranged to record differentially between this ascending limbs (ALH) and ascending vasa recta (AVR), gave values of 1.95 +/- 0.17 mV, ALH positive, in hydropenia with mineral oil bathing the kidney. Average values remained in the range of 1-2 mV when the ALH and AVR values were obtained sequentially, when the kidney was bathed in Ringer solution, when 5-8 Momega Ling-Gerard microelectrodes were used in the ALH, or when the hamsters were in saline diuresis. These results contradict reports of earlier studies with high impedance Ling-Gerard electrodes that the PD was -9 mV, ALH negative. Perfusion of ALH in saline diuresis with solutions of various compositions provided estimates of ionic transport numbers: tNa+ = 0.33 +/- 0.01, tK+ = 0.00 +/- 0.02, tC1- = 0.67 +/- 0.02. When the perfusion solution was designed to have the same Na+, K+, and C1- concentrations as AVR plasma, the PD was 1.36 +/- .20 mV; when ouabain or furosemide were included (10(-5) M), the PD declined 1.35 +/- 0.21 mV and 1.41 +/- 0.28 mV, respectively. The results suggest that active C1- transport is mainly responsible for the PD, but that diffusion potentials can contribute.

Animals↗
PubMed1975

A model of NaCl and water flow through paracellular pathways of renal proximal tubules.

To explain how hydrostatic pressure differences between tubule lumen and interstitium modulate isotonic reabsorption rates, we developed a model of NaCl and water flow through paracellular pathways of the proximal tubule. Structural elements of the model are a tight junction membrane, an intercellular channel whose walls transport NaCl actively at a constant rate, and a basement membrane. Equations of change were derived for the channel, boundary conditions were formulated from irreversible thermodynamics, and a pressure-area relationship typical of thin-walled tubing was assumed. The boundary value problem was solved numerically. The principal conclusions are: 1) channel NaCl concentration must remain within a few mOsm of isotonic values for reabsorption rates to be modulated by transtubular pressure differences known to affect this system: 2) basement membrane and channel wall parameters determine reabsorbate tonicity; tight junction parameters affect the sensitivity of reabsorption to transmural pressure; 3) channel NaCl concentration varies inversely with transmural pressure difference; this concentration variation controls NaCl diffusion through the tight junction; 4) modulation of NaCl diffusion through the tight junction controls the rate of isotonic reabsorption; modulation of water flow can increase sensitivity to transmural pressure; 5) no pressure-induced change in permeability of the tight junction or basement membrane is needed for pressure to modulate reabsorption; and 6) system performance is indifferent to the distribution of active transport sites, to the numerical value of the compliance function, and to the relationship between lumen and cell pressures.

Basement Membrane↗
PubMed1975

Mechanism of NaCl reabsorption by hamster thin ascending limbs of Henle's loop.

Two models of ypertonic urine formation in the inner medulla were tested. The active model asserts that thin ascending limbs of Henle's loop (ALH) reasorb NaCl hypertonically by active transport; the passive model suggests the reabsorption is by diffusion down a concentration gradient. Using (Na+) in ascending vasa recta (AVR) as a measure of interstitial (Na+), we found no concentration difference between loop tubular fluid and AVR, when the comparison was made at the bend of the loop, or at an ALH sampling site 1 mm from the bend; the results were the same in antidiuresis and saline diuresis. In saline diuresis with flow of tubular fluid to the ALH slowed by simultaneous collection at the bend of the loop,ALH (Na+) fell below AVR levels, a result consistent with active transport, but not with a purely passive mechanism. Although contragradient transport was shown only with flow slowed and the corticomedullary gradient reduced, a model suggests the active component contributes almost half the observed Na+ flux in antidiuresis.

Animals↗
PubMed1975

Effects of diuretic states on collecting duct fluid flow resistance in the hamster kidney.

Hydrostatic pressures were measured in cortical tubules, long loops of Henle, terminal collecting ducts, and in vasa recta in hamsters. In hydropenia, the loops of Henle and terminal collecting ducts provided the major fluid flow resistances, as judged by the location of hydrostatic pressure drops. In mannitol or saline diuresis, hydrostatic pressures in all tubular segments increased, but pressure drops in loops of Henle disappeared, indicating dilatation of loops. The major pressure drop was in terminal collecting ducts, especially in ducts of Bellini, even though these tubular segments also dilated. At highest urine flows, cortical tubule pressures were higher with the ureter and renal pelvis intact than when they were excised, suggesting laminar flow in the ureter adds a flow resistance at high flows. The pressure drop across the medullary capillary bed was 1-2 mmHg. The summation of medullary capillary hydrostatic and colloid osmotic pressures favored fluid uptake from the interstitium, a relationship enhanced by vasa recta geometry which ensures that descending vasa recta offer 4 times the flow resistance of ascending vessels.

Animals↗
PubMed1971

Micropuncture studies of the electrochemical aspects of fluid and electrolyte transport in individual seminiferous tubules, the epididymis and the vas deferens in rats.

1. Micropuncture and micro-analytical techniques were used to study some of the electrochemical aspects of fluid and electrolyte transport in single seminiferous tubules, the epididymis and vas deferens.2. Seminiferous tubules contain a fluid that is slightly hypertonic to plasma, has a high potassium and chloride ion concentration, a lower sodium ion concentration and is slightly acidic relative to plasma.3. The lumen of the seminiferous tubule is about 5 mV negative to a Ringers bathing solution.4. Potassium and chloride ions enter the seminiferous tubule lumen against an electrochemical gradient, while the gradient for sodium ion favours its entry. This does not preclude possible active transport of sodium ion.5. Between the seminiferous tubules and the beginning of the caput epididymis spermatocrit changes indicate that about 50% of the fluid leaving the testis is reabsorbed. Chloride ion and potassium ion are reabsorbed in concentrations greater than in lumen while sodium ion is reabsorbed in a concentration equal to that in the lumen. This region is also the site of intense hydrogen ion secretion.6. The region between the seminiferous tubules and the caput is isopotential. Reabsorption of sodium and chloride ions are against electrochemical gradient. Potassium ion reabsorption is favoured by the electrochemical gradient.7. Osmolar and electrical considerations indicate the probable secretion of organic acids between the seminiferous tubules and the caput epididymis.8. Between the caput and the vas deferens 50% of the remaining fluid is reabsorbed. Sodium ion is reabsorbed in concentrations much greater than in lumen, potassium ion enters the lumen and the pH rises. Sodium reabsorption in this region is essentially independent of chloride reabsorption.9. The corpus epididymis is 20 mV negative to a Ringers bathing medium while the beginning of the vas deferens is 27 mV negative. Reabsorption of sodium ion is against an electrochemical gradient as is potassium entry. Osmolality data and the concentration of sodium in the reabsorbate require further secretion of organic compounds in this region.

Animals↗