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J M Sands

Publications and source records attributed to J M Sands.

At least 19 recordsLinked to original sources
PubMed1992

Characteristics of osmolarity-stimulated urea transport in rat IMCD.

Urea transport across the terminal inner medullary collecting duct (IMCD) is mediated by a urea transporter that is stimulated by vasopressin (AVP) or hyperosmolarity. To determine whether hyperosmolarity stimulates urea transport by an adenylyl cyclase-dependent or -independent mechanism, terminal IMCDs were perfused with 10 microM forskolin followed by an increase in osmolality or with increasing osmolality followed by 10 nM AVP. In both protocols, stimulating adenylyl cyclase caused an additive increase in urea permeability (Purea) to that stimulated by hyperosmolarity. Next, we investigated whether hyperosmolarity stimulates the same urea transporter as AVP by studying the inhibitor profile and IMCD subsegment response of hyperosmolarity-stimulated urea transport and comparing it to properties already demonstrated for AVP-stimulated urea transport. In terminal IMCDs, luminal phloretin (250 microM) reversibly inhibited Purea by 63%. Thiourea (100 mM) inhibited Purea by 73% at two different levels of osmolality, 690 and 290 mosmol/kgH2O. The half-maximal inhibitory concentration (K1/2) for thiourea at 690 mosmol/kgH2O was not significantly different from the K1/2 value at 290 mosmol/kgH2O, suggesting that stimulation by hyperosmolarity is related to an increase in the Vmax for the urea transporter. Finally, we found that hyperosmolarity did not stimulate Purea in the initial IMCD. In summary, the data suggests that hyperosmolarity stimulates urea transport by an adenylyl cyclase-independent mechanism. However, the inhibitor profile and the IMCD subsegment response for hyperosmolarity-stimulated and AVP-stimulated Purea are similar, suggesting that both hyperosmolarity and AVP stimulate the same urea transporter.

Adenylyl Cyclases↗
PubMed1992

Maturation of aldose reductase expression in the neonatal rat inner medulla.

Newborns are less able to concentrate urine than adults are. With development of the concentrating system and a hypertonic medullary interstitium, there is a need to generate intracellular osmolytes such as sorbitol, which is produced in a reaction catalyzed by the enzyme aldose reductase. We sought to discriminate between two possible mechanisms of aldose reductase induction during development: (a) a response to an osmotic stimulus generated by the concentrating mechanism; or (b) part of the genetic program for development of the kidney. We measured the change in aldose reductase mRNA and activity in terminal inner medullary collecting ducts (IMCDs) microdissected from Sprague-Dawley rats during the first month of life. Aldose reductase mRNA was assayed by Northern analysis of total RNA from inner medulla and by detection of the reverse transcription-polymerase chain reaction (RT-PCR) product obtained from single IMCDs using aldose reductase-specific primers. Aldose reductase activity was measured in IMCDs taken from the same rats using a fluorescent microassay. Newborn rat IMCDs had minimal aldose reductase mRNA or activity, however mRNA was readily detected in IMCDs from rats older than 3 d of age, with peak expression occurring at 1-3 wk of age before decreasing to adult levels. In contrast, the mRNA level for a housekeeping metabolic enzyme, malate dehydrogenase, did not change during maturation. Aldose reductase enzyme activity was readily detectable by 6 d of age, peaked at 20 d, then decreased to adult levels. Urine osmolality remained < 600 mosmol/kg until 16 d, then increased to > 1,100 mosmol/kg after 20 d. Thus, aldose reductase mRNA and activity increased before urinary osmolality reached 870 mosmol/kg. Because urine osmolality may not be indicative of inner medullary osmolality and because mother's milk may provide excessive free water to the pups under 3 wk of age, half of the animals in several litters were separated from their mothers for 1 d and inner medullary osmolality, in addition to urine osmolality, was measured by vapor pressure osmometry, while aldose reductase mRNA was assessed densitometrically in IMCDs after RT-PCR. Although fluid restriction resulted in a near doubling of urine osmolality and a tendency towards increased aldose reductase mRNA, there was no consistently significant increase in aldose reductase mRNA or inner medullary osmolality during the first 13 d of life compared to the suckling animals. On the other hand, 2-3-wk-old rats showed significant increases in aldose reductase mRNA, accompanied by increases in inner medullary osmolality, after fluid restriction. Thus, the dissociation between the increases in aldose reductase expression and inner medullary hyperosmolality indicates that the maturational induction of the aldose reductase gene is not a consequence of osmotic stimulation, but rather, part of the developmental program of the kidney.

Aldehyde Reductase↗
PubMed1992

Urinary concentrating ability in patients with Jk(a-b-) blood type who lack carrier-mediated urea transport.

Water homeostasis is regulated in large part by the proper operation of the urinary concentrating mechanism. In the renal inner medulla, urea recycling from the inner medullary collecting duct to the inner medullary interstitium is thought to be essential for the production of a concentrated urine; however, it has not been possible to test this hypothesis in humans. Recently, a unique combination of genetic abnormalities has been described: absence of Kidd blood group antigens and absence of carrier-mediated urea transport in erythrocytes. Because animal studies indicate a similarity between urea transport in red blood cells and the nephron, it was postulated that patients without the Kidd antigen might lack facilitated urea transport in their kidneys. Hence, their ability to concentrate urine maximally was measured. Current models of nephron function would predict that in the complete absence of urea transport, the maximal concentrating ability would be around 800 to 900 mosM/kg H2O. Two homozygous patients had a moderate decrease in maximal concentrating ability (UosM,max = 819 mosM/kg H2O); a heterozygote also had some limitation. These studies raise the possibility that the erythrocyte urea transporter and the kidney urea transporter are encoded by a single gene (detected by the mutational loss of the Kidd antigen) and that a lack of facilitated urea transport impairs urea recycling in the kidney and, hence, maximal urinary concentrating ability.

Adolescent↗
PubMed1991

An independent effect of osmolality on urea transport in rat terminal inner medullary collecting ducts.

We have shown that urea transport across the terminal inner medullary collecting duct (terminal IMCD) is mediated by a vasopressin-stimulated, facilitated diffusion process exhibiting properties consistent with a transporter. To investigate whether hypertonic NaCl, as exists in vivo in the inner medulla, affects urea permeability, we studied isolated perfused rat terminal IMCD segments. Perfusate and bath osmolality were varied symmetrically by adding or removing NaCl or mannitol. Urea permeability rose progressively when osmolality was increased with NaCl or mannitol from 290 to 690 mOsm/kg H2O in the absence of vasopressin; there was no further increase at 890 mOsm/kg H2O. In the presence of 10(-8) M arginine vasopressin, urea permeability increased when NaCl was added to raise osmolality from 290 to 490 mOsm/kg H2O but there was no further increase at 690 mOsm/kg H2O. When 1 mM 8-bromo cyclic AMP was added to the bath, raising NaCl still increased urea permeability. These results suggest that urea transport across the rat terminal IMCD is regulated both by vasopressin and by osmolality at values present in the renal inner medulla. Osmolality seems to activate urea transport across the rat terminal IMCD by mechanisms distinct from those of vasopressin or cyclic AMP.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1991

Atrial natriuretic factor does not improve the outcome of cadaveric renal transplantation.

Atrial natriuretic factor (ANF) ameliorates renal damage in animal models of acute ischemic renal failure. Consequently, ANF could blunt acute tubular necrosis related to ischemia that occurs frequently in cadaveric renal transplants. Ten pairs of cadaveric kidneys were transplanted into 20 recipients. Paired recipients received either alpha-human ANF (hANF) or vehicle alone in a prospective, double-blind protocol. Upon revascularization of the allograft, either hANF or vehicle was administered intravenously as a 50-micrograms bolus, followed by a 4-h infusion (0.1 microgram/kg/min). Glomerular filtration rate ([125I]iothalamate clearance) was measured between 4 and 7 days posttransplant and again between 14 and 21 days posttransplant. Serum creatinine was measured daily when patients were in the hospital, then twice weekly as patients were examined in the outpatient clinic. Between the groups, there was no significant difference in age of the recipients or donors, cold ischemia time, or histocompatibility leukocyte antigen match. Infusion of hANF had no adverse effects. When subjects receiving hANF were compared with those treated with vehicle alone, there were no significant differences in serum creatinine or glomerular filtration rate. Three hANF and four vehicle recipients required dialysis postoperatively. At 1 month posttransplant, 19 of 20 patients had functioning allografts; an allograft from one hANF recipient never functioned. It was concluded that hANF, when given by the protocol of this study, had no beneficial effect on the outcome of cadaveric renal transplantation in humans.

Acute Kidney Injury↗
PubMed1991

Acute changes in intracellular ions or pH and regulation of aldose reductase activity.

Sorbitol production in the renal medulla increases in dehydrated rats, indicating that aldose reductase activity varies with the state of hydration. This response could be due to an increased synthesis of the enzyme (Moriyama T et al. J Biol Chem 1989:264:16810-16814) and/or a change in aldose reductase activity caused by acute changes in intracellular ionic composition, ionic strength, osmolality, or pH. Aldose reductase activity in tubules dissected from kidneys of control rats and rats undergoing water diuresis was measured, and the tubules were permeabilized so that changes in intracellular composition that would occur during dehydration could be induced experimentally. Aldose reductase activity did not change consistently as sodium, potassium, chloride, or osmolality were varied. Aldose reductase activity did increase acutely when sulfate was raised or when pH was lowered to pH 6.2 to 6.8, corresponding to the pH optimum of the enzyme. The small magnitude of change in enzyme activity suggests that the major influence of dehydration on aldose reductase activity is to increase enzyme synthesis. It was concluded that aldose reductase activity is not acutely regulated by changes in sodium, potassium, chloride, or osmolality. The stability of aldose reductase activity despite changes in ionic composition or osmolality supports the hypothesis that acute regulation of intracellular sorbitol content occurs by variation in cell sorbitol permeability and not by variation in cell sorbitol production.

Aldehyde Reductase↗
PubMed1991

Effects of moon phase and other temporal variables on absenteeism.

Previous research on the effects of lunar phase on deviant behavior has produced weak and inconsistent results and has been criticized for failing to use appropriate statistical controls. This study examined the effects of the full moon on daily absenteeism rates in a large organization while correcting for autocorrelation and controlling for the effects of the day of the week, month, and proximity to a holiday. Contrary to expectations, the full moon was associated with a significant (but very slight) decrease in absenteeism. Reasons for persistent beliefs in the effects of the full moon are discussed.

Absenteeism↗
PubMed1990

Countercurrent system.

Urinary concentration is achieved by countercurrent multiplication in the inner medulla. The single effect in the outer medulla is active NaCl absorption from the thick ascending limb. While the single effect in the inner medulla is not definitively established, the majority of experimental data favors passive NaCl absorption from the thin ascending limb. Continued experimental studies in inner medullary nephron segments will be needed to elucidate fully the process of urinary concentration.

Animals↗
PubMed1990

Hemolytic-uremic syndrome following "crack" cocaine inhalation.

The authors present a patient who experienced cocaine-related thrombotic microangiopathy and patchy renal cortical necrosis, associated with the clinical syndrome of microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure, characteristics of the Hemolytic-Uremic syndrome. The proposed pathogenetic mechanisms include: (1) cocaine-induced vasoconstriction and endothelial damage and (2) procoagulant effects of cocaine.

Administration, Inhalation↗
PubMed1990

Net acid transport by isolated perfused inner medullary collecting ducts.

The isolated perfused tubule technique was used to study net acid transport in rat terminal inner medullary collecting duct (IMCD) segments. The stop-flow luminal pH [measured fluorometrically with the acidic form of the pH-sensitive dye 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein in the lumen] fell 0.35 units below the bath pH in tubules from control rats and 0.53 units below the bath in tubules from deoxycorticosterone-treated rats. Tubules from control rats absorbed bicarbonate and secreted ammonium against concentration gradients, although at low rates. In control rats, 10(-8) M vasopressin added to the bath increased bicarbonate absorption almost threefold. Treatment of rats in vivo with deoxycorticosterone significantly increased the rate of bicarbonate absorption in vitro. In vivo NH4Cl loading also significantly increased bicarbonate absorption. Staining microdissected tubules with acridine orange confirmed that the perfused segments lacked intercalated cells. We conclude that the terminal IMCD spontaneously acidifies the lumen despite an absence of intercalated cells. Bicarbonate absorption appears to be regulated by the same factors that affect net acidification in other collecting duct segments.

Absorption↗
PubMed1990

Concentration dependence of urea and thiourea transport in rat inner medullary collecting duct.

The vasopressin-dependent urea permeability of the rat terminal inner medullary collecting duct (IMCD) is much greater than can be explained by lipid-phase permeation or paracellular diffusion, suggesting the presence of vasopressin-stimulated facilitated transport pathway. We used the isolated perfused tubule technique to test whether the urea transport pathway exhibits saturation characteristics consistent with a facilitated pathway. When the luminal urea concentration was varied between 0 and 800 mM (no urea in peritubular bath), the relationship between the urea flux and the luminal concentration was linear with a y-axis intercept that was not significantly different from zero, indicating an absence of saturation in this concentration range. Higher concentrations of urea could not be tested due to technical limitations. However, when thiourea (a urea analogue that shares the urea transport pathway with urea) was substituted for urea in similar experiments, the apparent thiourea permeability fell with increasing thiourea concentration in the range 10-200 mM, indicative of saturation of the urea-thiourea transporter. When the urea concentration was varied in both bath and lumen, the lumen-to-bath urea flux approached a limiting value at 400-500 mM urea, consistent with saturation of the transporter. However, nonspecific inhibition of urea transport by bath urea could not be ruled out in those experiments. We conclude that the urea and thiourea transport pathway in the terminal IMCD exhibits saturation characteristics. However, the urea concentration required to saturate the pathway is apparently high, at least 400-500 mM in one set of experiments and probably greater than 800 mM in another.

Animals↗
PubMed1990

Urea gradient-associated fluid absorption with sigma urea = 1 in rat terminal collecting duct.

It has been proposed that inner medullary collecting ducts (IMCDs) can absorb fluid in the absence of a transepithelial osmolality gradient if a perfusate-to-bath urea gradient is present. Such a process has been suggested to be caused by a nonunity reflection coefficient for urea (sigma urea less than 1). However, our recent measurements of sigma urea yielded values not significantly different from 1.0. The present study was done to readdress the possibility of direct coupling of water and urea transport in the rat IMCD. Isolated rat terminal IMCD segments were studied in the presence of 10(-10) M vasopressin with the osmolality of the perfusate equal to that of the peritubular bath but with a perfusate-to-bath urea gradient (bath osmolality balanced with NaCl). We measured both fluid absorption rate and urea concentration in collected fluid and calculated the osmolality of the collected fluid. We observed rapid fluid absorption associated with substantial urea absorption. The urea absorption caused a large fall in the osmolality of the collected fluid with respect to the bath. Simulations with a mathematical model of an isolated perfused tubule revealed that the transepithelial osmolality gradient generated along the length of tubule (caused by urea absorption) was large enough to account for the fluid absorption. Measurement of sigma urea with the "zero-flux" (or null point) method revealed a value of 1.00 +/- 0.02. Thus we conclude that the observed fluid absorption is the result of a transepithelial osmolality gradient generated by rapid urea absorption and does not require sigma urea less than one.

Absorption↗
PubMed1990

Coordinated response of renal medullary enzymes regulating net sorbitol production in diuresis and antidiuresis.

The renal response to changes in hydration includes variation in intracellular sorbitol, a major inner medullary osmolyte. To examine the mechanism for changes in net sorbitol production, we measured activities of enzymes regulating sorbitol production (aldose reductase) and degradation (sorbitol dehydrogenase) in untreated, water diuretic, and antidiuretic (water restriction and/or vasopressin administration) rats. Collecting duct segments dissected from collagenase-treated kidneys of Sprague-Dawley rats were divided into outer medullary and three distinct inner medullary regions. Aldose reductase activity increased during antidiuresis and decreased during diuresis. In contrast, sorbitol dehydrogenase activity was very low during antidiuresis and increased during diuresis. These changes in enzyme activity were found after 3 days, but not after 1 day, of water diuresis/antidiuresis. Enzyme activity changed only in the deepest 50% of the inner medullary collecting duct. Thus, there is coordinated regulation of aldose reductase and sorbitol dehydrogenase activities so that (a) during water diuresis, aldose reductase activity decreases while sorbitol dehydrogenase activity increases; and (b) during antidiuresis (water restriction and/or vasopressin administration), aldose reductase activity increases while sorbitol dehydrogenase activity remains low. We conclude that long-term osmoregulation in response to physiologic stimuli involves both aldose reductase and sorbitol dehydrogenase activities in rat terminal inner medullary collecting duct segments.

Aldehyde Reductase↗
PubMed1989

ANF inhibits NaCl and fluid absorption in cortical collecting duct of rat kidney.

Atrial natriuretic factor (ANF) is a peptide hormone that causes a large increase in urinary sodium chloride and water excretion when its plasma concentration rises above basal levels. As yet, there is no consensus regarding the chief site of action of ANF in the kidney. We microdissected and perfused rat cortical collecting ducts in vitro to determine whether ANF-(1-28) can directly inhibit net sodium and fluid absorption. ANF decreased both net sodium absorption and vasopressin-stimulated net fluid absorption by 50-90% when added to the peritubular bath solution. Approximately 50% inhibition of net fluid absorption occurred at 0.1 nM ANF, a level equivalent to plasma concentrations in volume-expanded rats. The action of ANF was mimicked by the addition of exogenous guanosine 3',5'-cyclic monophosphate. If ANF has a similar action on the cortical collecting duct in vivo, it could account for a substantial part of the ANF-mediated increase in urinary sodium and water excretion.

Animals↗
PubMed1989

Aldose reductase activities in microdissected rat renal tubule segments.

Osmoregulation in inner medullary cells depends in part on cellular accumulation of sorbitol, the production of which from glucose is catalyzed by aldose reductase. To identify nephron segments that contain aldose reductase, we developed a fluorometric ultramicroassay to measure aldose reductase activity in microdissected nephron segments from collagenase-treated kidneys of Sprague-Dawley rats. DL-Glyceraldehyde (10 mM) was used as a substrate. Substantial aldose reductase activities were found in all three inner medullary renal tubule segments: thin descending limbs, thin ascending limbs, and inner medullary collecting ducts. Activity increased with depth into the inner medulla in all three segments. When aldose reductase activities were normalized by cell volume the activities in the three inner medullary segments were similar. Little or no aldose reductase activity was measured in glomeruli or any cortical or outer medullary nephron segment. Both proximal convoluted and proximal straight tubules were found to have a substantial capacity to reduce DL-glyceraldehyde, but the finding of greater reductase activity with D-glucuronate (10 mM) than with D-xylose (10 mM) indicated that the activity was due to aldehyde reductase. Sorbitol dehydrogenase (measured by a similar ultramicroassay method) was present in substantial amounts in proximal tubules, but not in inner medullary collecting ducts. The overall pattern of enzyme activities is consistent with the proposed osmoregulatory role for sorbitol in all three inner medullary renal tubule segments.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehyde Reductase↗
PubMed1989

Independence of urea and water transport in rat inner medullary collecting duct.

Several published models of the renal concentration mechanism have assumed a reflection coefficient for urea in the inner medullary collecting duct (IMCD) that is less than unity, implying direct coupling between water and urea transport. In the present study, we used isolated perfused terminal IMCD segments and mathematical modeling of IMCD transport to determine the validity of this assumption. Mathematical simulations of IMCD transport, using recently published data on urea and water permeability, revealed that the method previously used to measure the reflection coefficient for urea underestimates the true value. The modeling results allowed us to design two new experimental protocols to determine the reflection coefficient for urea. In the first protocol, we measured the ability of a transepithelial urea gradient to induce a water flux, correcting for the dissipation of the urea gradient by rapid passive urea permeation. In the second protocol, we directly measured the solvent drag of urea resulting from an osmotically induced water flux. Both protocols yielded values for the urea reflection coefficient that were not significantly different from unity (0.92 +/- 0.04 and 1.07 +/- 0.05, respectively). Thus we find no evidence for direct coupling between urea and water transport in the rat terminal IMCD.

Animals↗
PubMed1989

Chloride and osmotic water permeabilities of isolated rabbit renal papillary surface epithelium.

The papillary surface epithelium (PSE) covers the mammalian renal papilla. It has been proposed that water or solute fluxes across the PSE might result in changes in urine or medullary interstitial fluid composition. To study osmotic water and chloride permeabilities, the PSE was dissected from underlying medullary tissue and mounted in a small Ussing chamber. Osmotic water permeability was low (14.2 +/- 3.0 microns/s) and was unaffected by 100 nM vasopressin added to the basolateral surface. In contrast, the PSE showed a substantial chloride permeability of 3.1 +/- 0.4 x 10(-5) cm/s that decreased reversibly to 2.2 +/- 0.3 x 10(-5) cm/s (P less than 0.01) with vasopressin. Vasopressin also reversibly increased the transepithelial resistance of the PSE from 87 +/- 9 to 106 +/- 13 omega.cm2 (P less than 0.02). Apical bumetanide (10(-6) M) had no significant effect on PSE chloride permeability. The apparent Na-Cl permeability ratio (0.75 +/- 0.01) calculated from dilution potential measurements was not affected significantly by vasopressin or apical bumetanide. We conclude that it is unlikely that physiologically significant osmotic water fluxes occur across the papillary surface epithelium. However, the NaCl permeability is sufficiently high that physiologically significant transepithelial NaCl fluxes could occur under conditions associated with reflux of urine backward from the papillary tip.

Animals↗