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D A Maddox

Publications and source records attributed to D A Maddox.

31 records · Page 2Linked to original sources
PubMed1982

PCO2 measurements in surface proximal tubules and peritubular capillaries of the rat kidney.

PCO2 was measured in surface proximal tubules and peritubular capillaries in the rat under normal acid-base conditions and in three settings with decreased HCO3(-) reabsorption: benzolamide administration, respiratory alkalosis, and metabolic acidosis. Under normal conditions, PCO2 in the early proximal tubule (EP) was 10.5 mmHg higher than PaCO2 (P less than 0.001) and 3-4 mmHg higher than late proximal (LP) and peritubular capillary (PC) PCO2 (P less than 0.001). PCO2 in LP and PC was 7 mmHg higher than PaCO2 (P less than 0.001). Benzolamide (3 mg/kg) had no effect on the difference between PC and arterial PCO2 or between EP and PC PCO2. Increasing benzolamide to 8 mg/kg increased PCO2 in the surface structures relative to arterial PCO2 by 3-5 mmHg (P less than 0.01). Metabolic acidosis did not alter the relationships between cortical and arterial PCO2. By contrast, respiratory alkalosis decreased cortical PCO2 relative to PaCO2 by over 50%. Nonetheless, EP PCO2 was still higher than LP or PC PCO2 (P less than 0.01). Thus, reducing HCO3(-) reabsorption does not obliterate the difference between EP and LP or PC PCO2 nor does it invariably reduce PCO2 in the surface structures of the kidney relative to arterial PCO2.

Animals↗
PubMed1979

Maturational development of glomerular ultrafiltration in the rat.

To ascertain the cause of low glomerular filtration rate in newborn and immature mammals, we measured glomerular pressures and flows directly in immature (30- to 45-day-old) euvolemic Munich-Wistar rats with surface glomeruli. As with total kidney GFR, single nephron (SN)GFR was found to be significantly lower than in adult rats, on average by 40% when corrected for kidney weight. Equality between efferent oncotic pressure and transglomeruler hydraulic pressure difference (deltaP) was usually achieved in immature rats, indicating that the glomerular capillary ultrafiltration coefficient is not a factor limiting SNGFR and GFR in immature rats. Although the average values for deltaP in immature rats were slightly, albeit significantly, lower than in adults, markedly lower values (79 +/- 5 vs. 136 +/- 10 nl/min per g kidney wt) for glomerular plasma flow rate (QA) proved to be the primary factor responsible for the lower SNGFR and GFR values in immature rats. Considerably higher values for afferent and efferent arteriolar resistances contributed to this low QA state in immature rats.

Aging↗
PubMed1979

Control of proximal bicarbonate reabsorption in normal and acidotic rats.

This free-flow micropuncture study examined the dependence of bicarbonate reabsorption in the rat superficial proximal convoluted tubule to changes in filtered bicarbonate load, and thereby the contribution of the proximal tubule to the whole kidney's response to such changes. The independent effects of extracellular fluid (ECF) volume expansion and of acidosis on proximal bicarbonate reabsorption were also examined. When the plasma volume contraction incurred by the micropuncture preparatory surgery was corrected by isoncotic plasma infusion ( congruent with1.3% body wt), single nephron glomerular filtration rate (SNGFR), and the filtered total CO(2) load increased by 50%. Absolute proximal reabsorption of total CO(2) (measured by microcalorimetry) increased by 30%, from 808+/-47 during volume contraction to 1,081+/-57 pmol/min.g kidney wt after plasma repletion, as fractional total CO(2) reabsorption decreased from 0.90 to 0.77. Aortic constriction in these plasma-repleted rats returned the filtered load and reabsorption of total CO(2) to the previous volume contracted levels. In other animals isohydric ECF expansion with plasma (5% body wt) or Ringer's solution (10% body wt), or both, produced no further diminution in fractional proximal total CO(2) reabsorption (0.76-0.81). Metabolic acidosis was associated with very high fractional proximal total CO(2) reabsorptive rates of 0.82 to 0.91 over a wide range of SNGFR and ECF volumes. At a single level of SNGFR, end-proximal total CO(2) concentration progressively decreased from 5.6+/-0.5 to 1.6 +/-0.2 mM as arterial pH fell from 7.4 to 7.1. Expansion of ECF volume in the acidotic rats did not inhibit the ability of the proximal tubule to lower end-proximal total CO(2) concentrations to minimal levels. In conclusion, bicarbonate reabsorption in the superficial proximal convoluted tubule is highly load-dependent (75-90%) in normal and acidotic rats. No inhibitory effect of ECF volume per se on proximal bicarbonate reabsorption, independent of altering the filtered bicarbonate load, could be discerned. Acidosis enabled the end-proximal luminal bicarbonate concentration to fall below normal values and reduced distal bicarbonate delivery.

Absorption↗
PubMed1977

Effects of surgery on plasma volume and salt and water excretion in rats.

Surgical preparation of rats for micropuncture resulted in a marked decrease in sodium excretion (UNaV) compared to awake animals. Associated with surgery, hematocrit (Hct) rose. Studies were performed to determine whether the rise in Hct resulted from reduced plasma volume (PV) or increased red cell volume (RCV) and to explore the relation of such alterations to the fall in UNaV. PV and RCV were determined in the calm awake rat using 125I-albumin and 51Cr-labeled red blood cells. Micropuncture surgery was performed and RCV, PV, and Hct again measured. After anesthesia and femoral artery catheterization, Hct was not different from Hct in awake animals (42.9 +/- 2.8%). The Hct increased following surgery to 48.2 +/- 2.8% (P less than 0.001), accompanied by a large fall in PV (-18.9 +/- 2.3%, P less than 0.001) with no change in RCV. Plasma volume repletion to awake values restored UNaV toward levels appropriate for dietary intake in animals on a high salt diet. Althouth plasma repletion slightly increased UNaV above awake values in low salt diet rats, they continued to avidly retain salt with respect to total salt load.

Anesthesia↗
PubMed1975

Determinants of glomerular filtration in experimental glomerulonephritis in the rat.

Pressures and flows were measured in surface glomerular capillaries, efferent arterioles, and proximal tubules of 22 Wistar rats in the early autologous phase of nephrotoxic serum nephritis (NSN). Linear deposits of rabbit and rat IgG and C3 component of complement were demonstrated in glomerular capillary walls by immunofluorescence microscopy. Light microscopy revealed diffuse proliferative glomerulonephritis, and proteinuria was present. Although whole kidney and single nephron glomerular filtration rate (GFR) in NSN (0.8 plus or minus 0.04 SE2 ml/min and 2 plus or minus 2 nl/min, respectively) remained unchanged from values in 16 weight-matched NORMAL HYDROPENIC control rats (0.8 plus or minus 0.08 and 28 plus or minus 2), important alterations in glomerular dynamics were noted. Mean transcapillary hydraulic pressure difference (deltaP) averaged 41 plus or minus 1 mm Hg in NSN versus 32 plus or minus 1 in controls (P LESS THAN 0.005). Oncotic pressures at the afferent (piA) end of the glomerular capillary were similar in both groups ( 16 mm /g) but increased much less by the efferent end (piE) in NSN (to 29 plus or minus 1 mm Hg) than in controls (33 plus or minus 1, P less than 0.025). Hence, equality between deltaP and piE, denoting filtration pressure equilibrium, obtained in control but not in NSN rats. While glomerular plasma flow rate was slightly higher in NSN (88 plus or minus 8 nl/min) than in controls (76 plus or minus 6, P greater than 0.2), the failure to achieve filtration equilibrium in NSN rats was primarily the consequence of a marked fall in the glomerular capillary ultrafiltration coefficient, Kf, to a mean value of 0.03 nl/(s times mm Hg), considerably lower than that found recently for the normal rat, 0.08 nl/(s times mm Hg). Thus, despite extensive glomerular injury, evidenced morphologically and by the low Kf, GFR remained normal. This maintenance of GFR resulted primarily from increases in deltaP, which tended to increase the net driving force for filtration, and thereby compensate for the reduction in Kf.

Animals↗
PubMed1975

Control of proximal tubule fluid reabsorption in experimental glomerulonephritis.

We have recently shown that in the early autologous phase of nephrotoxic serum nephritis (NSN) single nephron glomerular filtration rate is unchanged from values in normal hydropenic control rats, but that single nephron filtration fraction and efferent arteriolar oncotic pressure (piE) are reduced because of a marked reduction in the glomerular capillary ultrafiltration coefficient. The present study was undertaken to examine the influence of this decline in piE as well as the other known determinants of peritubular capillary fluid exchange on absolute proximal fluid reabsorption (APR) in NSN. The findings indicate that APR and proximal fractional reabsorption are reduced significantly in NSN, relative to values in a separate group of age and weight-matched normal hydropenic control rats studied concurrently. In addition to the measured decline in piE, efferent arteriolar plasma flow (Qe) and peritubular capillary hydraulic pressure (Pc) were found to increase significantly, while interstitial oncotic pressure, estimated from hilar lymph, was not significantly different from values in control rats. Using a mathematical model of peritubular capillary fluid uptake we found that, assuming that the capillary permeability-surface area product and interstitial hydraulic pressure are unchanged in NSN, the observed changes in piE and Pc are sufficient to offset the effect of the increase in QE, yielding a calculated reduction in APR of approximately 4 nl/min, in excellent agreement with the observed mean decline of 4.1 nl/min. These findings suggest that control of APR in NSN is mediated by the same factors that regulate APR under normal physiological conditions, namely, the imbalance of forces governing peritubular capillary uptake of isotonic reabsorbate.

Animals↗
PubMed1974

Current concepts of sodium chloride and water transport by the mammalian nephron.

The decision of the editors to solicit a review for the Medical Progress series of this journal devoted to current concepts of the renal handling of salt and water is sound in that this important topic in kidney physiology has recently been the object of a number of new, exciting and, in some instances, quite unexpected insights into the mechanisms governing sodium excretion. These developments have come about largely as a consequence of the fact that segments of nephrons previously inaccessible to direct study are now readily accessible. Many of the findings to be discussed argue for extensive revision of a number of our current widely held views concerning the renal handling of sodium chloride and water. In the opinion of the authors, the strength of this argument rests in the fact that many of these new findings were obtained under circumstances that enabled workers to gain more direct access to the nephron than has been possible heretofore. This is not to say that areas of controversy and disagreement no longer exist. Wherever possible, these have been identified. In attempting to provide a comprehensive review of this topic, it has been necessary at times to overgeneralize and to disregard minor deficiencies in some of the studies cited. Finally, we wish to emphasize that a considerable portion of the information contained herein derives from work still under active investigation. Much of this contemporary work will undoubtedly withstand the rigors of future experimental scrutiny. It is inevitable, however, as William James so aptly noted in the quotation cited below, that some of our present ideas will need to be abandoned or revised in favor of newer, more convincing evidence. Seen in this light, the present effort is intended as nothing more than a timely survey of this active and fertile topic in renal physiology.

Animals↗
PubMedDate not supplied

Cryofixation, cryosubstitution, and immunoelectron microscopy: potential role in diagnostic pathology.

In immunoelectron microscopic investigations, retention of antigenic sites is crucial. Methods for preparing samples for conventional electron microscopy involve chemical fixatives followed by dehydration in organic solvents and embedding in plastic resins, all procedures potentially detrimental to antigenicity. Cryomethods provide a physical fixation alternative for the preparation of biological samples for ultrastructural, immunocytochemical, and microanalysis studies without the use of any chemicals. This can be particularly useful in diagnostic pathology, providing an alternative to conventional fixation methods which sometimes destroy the antigen in question. The recent development of a portable cryofixation device, the PS1000 Portable Metal Mirror Ultra-Rapid Cryofixation Unit (Delaware Diamond Knives, Inc., Wilmington, DE, USA), provides an opportunity to freeze tissue immediately after procurement for use in diagnostic immunocytochemistry studies. This feasibility study examined the quality of tissue preservation with this device, in terms of both preservation of cellular ultrastructure and immunolabeling. Human tonsil and thymus tissue was slam frozen and, after cryosubstitution in Lowicryl K11M, was examined by immunoelectron microscopy. Good ultrastructural preservation was obtained and reasonable immunolabeling with antibodies to AE1/AE3 keratin filaments was also observed.

Cryopreservation↗