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D W Good

Publications and source records attributed to D W Good.

At least 19 recordsLinked to original sources
PubMed1992

Effects of adenosine on ion transport in rat medullary thick ascending limb.

Previously, we demonstrated that adenosine (Ado) was released by the medullary thick ascending limb (MTAL) during hypoxia. The present experiments were designed to examine the effects of Ado and adenosine analogues on net chloride (JCl) and bicarbonate (JHCO3) absorption by the isolated, perfused MTAL of the rat. Ado, 10 nM, in the presence or absence of arginine vasopressin (AVP, 10(-10) M) reduced JCl by 50%. The inhibition of Ado was reproduced with the selective A1 agonist, N-6-phenylisopropyladenine (2 nM), and was reversed by 8-cyclopentyl-1,3-dipropylxanthine, an A1-receptor antagonist. Thus the inhibition of JCl is likely mediated through A1 receptors. In contrast, Ado had no effect on (JHCO3) either in the presence or absence of AVP. Ado also had no influence on the effect of AVP to inhibit JHCO3. The lack of effect on JHCO3 suggests that the inhibition of JCl by Ado is unlikely to be mediated through changes in cellular adenosine 3',5'-cyclic monophosphate. These results support the hypothesis that Ado released into the renal medulla during hypoxia may protect the MTAL from ischemic injury by directly inhibiting NaCl absorption and reducing transport-related oxygen consumption.

Absorption↗
PubMed1992

Effects of osmolality on bicarbonate absorption by medullary thick ascending limb of the rat.

UNLABELLED: Previously we demonstrated that arginine vasopressin (AVP) directly inhibits bicarbonate absorption (JHCO3, pmol/min per mm) in the medullary thick ascending limb (MTAL) of the rat. To determine whether changes in osmolality also may affect bicarbonate absorption, MTAL were studied in vitro with 25 mM HCO3- solutions. Control osmolality was 290 mosmol/kg H2O. In the absence of AVP, increasing osmolality to 560 in perfusate and bath by addition of 150 mM NaCl reduced JHCO3 from 13.7 to 4.5. With 2 x 10(-10) M AVP in the bath, adding 150 mM NaCl to perfusate and bath reduced JHCO3 from 6.9 to 0.6, while adding NaCl to the bath alone reduced JHCO3 from 7.1 to 0.5. Adding 150 mM NaCl to perfusate and bath caused a similar inhibition of JHCO3 in MTAL perfused with furosemide to inhibit net NaCl absorption. In the presence of AVP, adding 600 mM urea to perfusate and bath inhibited JHCO3 by 55%; adding 300 or 600 mM mannitol to perfusate and bath inhibited JHCO3 by 75%. The effects on JHCO3 were reversible and dissociable from changes in transepithelial voltage. CONCLUSIONS: (1) osmolality is a factor capable of regulating renal tubule bicarbonate absorption; (2) hypertonicity produced with NaCl, urea, or mannitol markedly inhibits bicarbonate absorption in the MTAL; (3) this inhibition occurs independent of, and is additive to, inhibition by vasopressin. Hypertonicity may shift TAL HCO3- absorption from medulla to cortex, thereby limiting delivery of bicarbonate to the medullary interstitium during antidiuresis.

Animals↗
PubMed1992

Chronic hyperkalemia impairs ammonium transport and accumulation in the inner medulla of the rat.

Previously we demonstrated in rats that chronic hyperkalemia had no effect on ammonium secretion by the proximal tubule in vivo but that high K+ concentrations inhibited ammonium absorption by the medullary thick ascending limb in vitro. These observations suggested that chronic hyperkalemia may reduce urinary ammonium excretion through effects on medullary transport events. To examine directly the effects of chronic hyperkalemia on medullary ammonium accumulation and collecting duct ammonium secretion, micropuncture experiments were performed in the inner medulla of Munich-Wistar rats pair fed a control or high-K+ diet for 7-13 d. In situ pH and total ammonia concentrations were measured to calculate NH3 concentrations for base and tip collecting duct and vasa recta. Chronic K+ loading was associated with significant systemic metabolic acidosis and a 40% decrease in urinary ammonium excretion. In control rats, 15% of excreted ammonium was secreted between base and tip collecting duct sites. In contrast, no net transport of ammonium was detected along the collecting duct in high-K+ rats. The decrease in collecting duct ammonium secretion in hyperkalemia was associated with a decrease in the NH3 concentration difference between vasa recta and collecting duct. The fall in the NH3 concentration difference across the collecting duct in high-K+ rats was due entirely to a decrease in [NH3] in the medullary interstitial fluid, with no change in [NH3] in the collecting duct. These results indicate that impaired accumulation of ammonium in the medullary interstitium, secondary to inhibition of ammonium absorption in the medullary thick ascending limb, may play an important role in reducing collecting duct ammonium secretion and urinary ammonium excretion during chronic hyperkalemia.

Ammonia↗
PubMed1991

Effects of graded oxygen tension on adenosine release by renal medullary and thick ascending limb suspensions.

Adenosine is released from renal cells, and extracellular adenosine may influence the effects of ischemia on medullary tubule segments by altering ion transport or renal hemodynamics. While adenosine release and excretion are enhanced during renal ischemia, the specific sites of renal adenosine production have not been completely elucidated. In the present study, extracellular adenosine concentrations in suspensions of renal outer medulla and thick ascending limb segments were quantitated by reversed-phase high performance liquid chromatography. Media from other medullary (OM) suspensions incubated for 8 and 15 minutes at 0% oxygen contained significantly greater amounts of adenosine (1.404 +/- 0.21 and 2.034 +/- 0.27 ng/micrograms protein, respectively), when compared to values obtained from media of suspensions incubated for equivalent periods under non-hypoxic conditions (8, 20, and 95% oxygen), 0.78 +/- 0.05 (8 min) and 1.37 +/- 0.21 ng/micrograms protein (15 min). Similarly, adenosine release was greater in medullary thick ascending limb (mTAL) suspensions incubated for 8 minutes at 0% versus 8% oxygen (0.81 +/- 0.17 vs. 0.20 +/- 0.12 ng/micrograms protein, respectively). Moreover, the observed increase in adenosine release by thick ascending limbs at 0% oxygen could be inhibited completely by either furosemide or ouabain. These studies demonstrate that: 1) the renal medulla and medullary thick ascending limb are sites of adenosine release; 2) adenosine release by the mTAL is enhanced significantly during hypoxic conditions; and 3) the increased release of adenosine during hypoxia appears to be related to ion transport and oxidative metabolism, as the increased release was prevented by two disparate inhibitors of transport in this segment.

Adenosine↗
PubMed1991

Effects of chronic hyperkalemia on renal production and proximal tubule transport of ammonium in rats.

Free-flow micropuncture experiments were performed to examine directly the effects of chronic hyperkalemia on renal ammonium production, urinary ammonium excretion, and proximal convoluted tubule ammonium transport in the rat in vivo. Munich-Wistar rats were pair-fed either a control or a high-K+ diet for 6-11 days. Chronic K+ loading was associated with an increase in plasma K+ concentration and significant systemic metabolic acidosis. Renal blood flow did not differ in control and high-K+ rats. In the hyperkalemic rats, urinary ammonium excretion was reduced by 40% and whole kidney ammonium production was reduced by 50% compared with controls. In contrast, chronic hyperkalemia had no significant effect on net ammonium transport by either the early or late segment of the proximal convoluted tubule. Chronic hyperkalemia also had no effect on the absolute rate of ammonium delivery to early or late proximal convoluted tubule sites. These results indicate that a change in renal ammonium production does not necessarily correlate with a change in proximal tubule ammonium transport and that reduced urinary ammonium excretion in chronic hyperkalemia is not due to impaired secretion of ammonium by the proximal convoluted tubule. Chronic hyperkalemia may reduce ammonium excretion by decreasing transfer of ammonium from proximal tubules to collecting ducts in the renal medulla.

Ammonia↗
PubMed1991

Ammonium transport in the kidney: new physiological concepts and their clinical implications.

This article is based on a Basic Science Symposium presented at the 23rd Annual Meeting of the American Society of Nephrology. New information on the segmental transport of ammonium by the proximal tubule, the thick ascending limb of Henle's loop, and the collecting duct is integrated into a thesis that NH4+ excretion is controlled by the rate of production, by diffusion of NH3 along gradients established by proton secretion, and by active transport of NH4+. These new concepts are applied to a novel explanation of the pathogenesis of distal renal tubular acidosis.

Acidosis, Renal Tubular↗
PubMed1990

Adaptation of HCO-3 and NH+4 transport in rat MTAL: effects of chronic metabolic acidosis and Na+ intake.

In vitro microperfusion experiments were performed to determine whether chronic metabolic acidosis or chronic alterations in sodium intake cause adaptive changes in bicarbonate or ammonium transport in the medullary thick ascending limb (MTAL) of the rat. In all experiments, MTAL were studied under standard conditions in vitro with 25 mM bicarbonate in perfusate and bath. Thus changes in transport rates reflect adaptive changes in the intrinsic transport properties of the tubule cells. Chronic metabolic acidosis (induced by oral NH4Cl loading) increased MTAL bicarbonate absorption by 53% and increased net ammonium absorption by 36%. Chronic administration of NaHCO3 (0.28 M NaHCO3 drinking H2O) increased MTAL bicarbonate absorption by 50% and increased net ammonium absorption by 54%, despite systemic metabolic alkalosis. Chronic administration of NaCl (0.28 M NaCl drinking H2O) also increased bicarbonate absorption by 50%. Thus an increase in sodium intake stimulated bicarbonate absorptive capacity to a similar extent when sodium was administered with either chloride or bicarbonate. Moderate dietary sodium restriction (0.5% NaCl) reduced bicarbonate absorption by 20% compared with pair-fed sodium-replete controls (2.2% NaCl). These results demonstrate that 1) the MTAL is a site of regulation of renal acid-base transport, 2) chronic metabolic acidosis is associated with adaptive increases in MTAL bicarbonate and ammonium absorption, changes that are appropriate to correct the acidosis, and 3) dietary sodium intake is an important determinant of MTAL bicarbonate and ammonium transport capacity. The response of the MTAL to changes in sodium intake suggests that this segment may play an important role in maintaining acid-base balance when NaCl intake is altered.

Acidosis↗
PubMed1990

Inhibition of bicarbonate absorption by peptide hormones and cyclic adenosine monophosphate in rat medullary thick ascending limb.

In vitro microperfusion experiments were performed to examine the effects of peptide hormones on bicarbonate and ammonium transport by the medullary thick ascending limb (MTAL) of the rat. Arginine vasopressin (AVP; 2.8 X 10(-10) M in the bath) reduced bicarbonate absorption by 50% (from 7.8 to 3.7 pmol/min per mm). AVP caused a similar reduction in bicarbonate absorption in tubules perfused with 10(-4) M furosemide to inhibit net NaCl absorption. Glucagon (2 X 10(-9) M in the bath) also reduced bicarbonate absorption (from 11.7 to 7.6 pmol/min per mm). The inhibition of bicarbonate absorption could be reproduced with either exogenous 8-bromo-cAMP or forskolin. With 8-bromo-cAMP (10(-3) M) in the bath, addition of vasopressin to the bath did not significantly affect bicarbonate absorption. PTH significantly inhibited bicarbonate absorption, but the extent of inhibition was less than that observed with either AVP or glucagon. Vasopressin had no effect on net ammonium absorption in MTAL perfused and bathed with 4 mM NH4Cl. These findings indicate that: (a) vasopressin, glucagon, and PTH directly inhibit bicarbonate absorption in the MTAL of the rat; (b) this inhibition occurs independent of effects on net NaCl absorption and appears to be mediated in part by cAMP; and (c) HCO3- and NH4+ absorption can be regulated independently in the MTAL.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1990

Ammonium transport by the loop of Henle.

Absorption of ammonium by the loop of Henle provides a mechanism by which ammonium produced and secreted by proximal tubules is transferred to collecting ducts in the renal medulla. Loop ammonium absorption is largely a result of active absorption of NH4+ by the thick ascending limb. Ammonium absorption in the thick ascending limb is mediated primarily by apical membrane Na(+)-NH4(+)-2Cl- cotransport, and provides a 'single effect' for countercurrent multiplication of ammonium in the renal medulla. Countercurrent multiplication causes ammonium to accumulate to high concentrations in the medullary interstitial fluid and generates a transepithelial concentration difference for NH3 that favors secretion of ammonium into medullary collecting ducts. Changes in systemic potassium balance and chronic metabolic acidosis influence ammonium excretion by regulating ammonium absorption in the medullary thick ascending limb and altering transfer of ammonium to medullary collecting ducts.

Absorption↗
PubMed1989

Regulation of acid-base transport in the rat thick ascending limb.

The thick ascending limb of the rat influences urinary net acid excretion by reabsorbing both bicarbonate and ammonium. The bicarbonate absorption is mediated predominantly by apical membrane Na+-H+ exchange and occurs at rates that are comparable to or greater than rates measured in cortical and medullary collecting ducts. The ammonium absorption is mediated predominantly by apical membrane Na+-NH4+-2Cl- cotransport and enhances urinary ammonium excretion by promoting countercurrent multiplication of ammonium, which facilitates ammonium secretion into medullary collecting ducts. Studies with medullary thick ascending limbs (MTAL) in vitro have shown that the regulation of these transport processes involves both acute responses to changes in the luminal and peritubular environment and adaptive changes in tubule transport capacity in response to chronic systemic acid-base perturbations. In particular, an increase in potassium concentration inhibits ammonium absorption with no effect on net bicarbonate absorption whereas vasopressin inhibits bicarbonate absorption with no effect on net ammonium absorption. Chronic metabolic acidosis causes an adaptive increase in the ability of the MTAL to reabsorb both bicarbonate and ammonium. These results demonstrate that the MTAL is a site of regulation of renal acid-base transport and that ammonium and bicarbonate transport rates can vary independently in this nephron segment.

Acid-Base Equilibrium↗
PubMed1988

Active absorption of NH4+ by rat medullary thick ascending limb: inhibition by potassium.

These experiments were designed to determine the relative contributions of active NH4+ transport and voltage-driven NH4+ diffusion to direct NH4+ absorption by the medullary thick ascending limb of the rat. Medullary thick ascending limbs were perfused in vitro with solutions containing 25 mM HCO3 and 4 mM total ammonia. Under steady-state conditions, the lumen-positive transepithelial voltage (VT) was not sufficient to account for the observed decrease in lumen NH4+ concentration, consistent with active absorption of NH4+. Flux calculations based on VT and measured NH4+ permeability (6 x 10(-5) cm/s) indicate that the majority (at least 65%) of total ammonia absorption is due to active transport of NH4+. The remainder of NH4+ absorption can be accounted for by voltage-driven diffusion. Increasing the potassium concentration from 4 to 24 mM in perfusate and bath markedly inhibited total ammonia absorption but did not affect VT, NH4+ permeability, or HCO3 absorption. These results are consistent with inhibition of the active component of NH4+ absorption by potassium. The active NH4+ absorption is likely mediated by cotransport of Na+, NH4+, and Cl- across the apical cell membrane. Inhibition of active NH4+ absorption by an increase in potassium concentration may be due, in part, to competition between NH4+ and K+ for a common binding site on the Na+ -K+ -2Cl- cotransport system.

Absorption↗