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W R Adam

Publications and source records attributed to W R Adam.

At least 37 records · Page 2Linked to original sources
PubMed1988

Problems in the assessment of magnesium depletion in the rat by in vivo 31P NMR.

Prior in vitro studies, utilizing 31P nuclear magnetic resonance (31P NMR) to measure the chemical shift (sigma) of beta-ATP and lengthening of the phosphocreatine spin-spin (T2) relaxation time, suggested an assessment of their efficacy in measuring magnesium depletion in vivo. Dietary magnesium depletion (Mg2+ decreases) produced markedly lower magnesium in plasma (0.44 vs 1.13 mmol/liter) and bone (130 vs 190 mumol/g) but much smaller changes in muscle (41 vs 45 mumol/g, P less than 0.01), heart (42.5 vs 44.6 mumol/g), and brain (30 vs 32 mumol/g). NMR experiments in anesthetized rats in a Bruker 7-T vertical bore magnet showed that in Mg2+ decreases rats there was a significant change in brain beta-ATP shift (16.15 vs 16.03 ppm, P less than 0.05). These chemical shifts gave a calculated free [Mg2+] of 0.71 mM (control) and 0.48 mM (Mg2+ decreases). In muscle the change in beta-ATP shift was not significant (Mg2+ decreases 15.99 ppm, controls 15.96 ppm), corresponding to a calculated free Mg2+ of 0.83 and 0.95 mM, respectively. Phosphocreatine T2 (Carr-Purcell, spin-echo pulse sequence) was no different with Mg2+ decreases in muscle in vivo (surface coil) (Mg2+ decreases 136, control 142 ms) or in isolated perfused hearts (Helmholtz coil) (control 83, Mg2+ decreases 92 ms). 31P NMR is severely limited in its ability to detect dietary magnesium depletion in vivo. Measurement of beta-ATP shift in brain may allow studies of the effects of interaction in group studies but does not allow prediction of an individual magnesium status.

Animals↗
PubMed1988

Potassium excretion in renal failure in the rat: the role of distal tubule flow and aldosterone.

1. This study examines the contribution of an increased distal tubule flow and of aldosterone to the handling of a potassium load in conscious rats with renal failure induced by subtotal nephrectomy or by gentamicin on a control of high K+ diet. 2. Glomerular filtration rate was reduced by subtotal nephrectomy to 40% and by gentamicin treatment to 60% of control. Subtotal nephrectomy induced significant hypertrophy of glomeruli and proximal and distal tubules, but gentamicin did not. Both experimental groups had a normal iothalamate space and plasma potassium after a 20 h fast. 3. Two hours after an acute KCl load rats with renal failure excreted less potassium than control rats. There was also a lesser natriuretic effect of KCl in the renal failure groups. 4. A high K+ diet, given for 5-7 days, increased excretion of an acute KCl load in control rats and rats with renal failure. 5. (UNaV + UKV) was used as an estimate of distal tubule flow. Potassium excretion, related to distal tubule flow, was similar in the renal failure and control rats when on the same diet. This is consistent with potassium excretion being strongly, but not necessarily solely, dependent on distal flow. 6. Adrenalectomy reduced, and aldosterone restored, potassium excretion in the renal failure and control groups. This suggests a role for aldosterone in excretion of an acute potassium load with this degree of renal failure.

Acute Kidney Injury↗
PubMed1988

Potassium adaptation: 39K-NMR evidence for intracellular compartmentalization of K+.

To investigate the effects of K+ uptake on the intracellular environment, both 39K-nuclear magnetic resonance (NMR) and K+-selective electrodes were used to measure K+ activity with acute K+ loading in control and K+-adapted rats. These results were then compared with tissue K+, measured by flame photometry. There was a lower NMR K+ visibility (ratio of NMR signal to tissue content) in muscle and liver in K+-adapted rats, compared with controls before and after an acute K+ load. This lower K+ visibility in K+-adapted rats was confirmed in liver homogenate with the K+-specific electrode. In liver homogenates from control and K+-adapted rats, addition of RbCl (300 mumol/g) increased the NMR K+ signal more in K+-adapted rats (19 +/- 1.1 mumol/g) than controls (11 +/- 1.0 mumol/g, P less than 0.01). This is consistent with the displacement of K+, by Rb+, from NMR-undetected sites. These results suggest that some 10-15% of intracellular K+ may be within a compartment not detectable by NMR or electrodes and that chronic K+ loading leads to an increased capacity of this compartment.

Adaptation, Physiological↗
PubMed1987

Measurement of tissue potassium in vivo using 39K nuclear magnetic resonance.

39K nuclear magnetic resonance (NMR) spectra were readily obtained, in vivo, from rat muscle, kidney, and brain in 5-10 min with signal-to-noise ratios of approximately 20:1. Quantitation of the K+ signal was achieved by reference to an external standard of KCl/dysprosium nitrate as well as by reference to the proton signal from tissue water. In vitro NMR studies of isolated tissue showed a K+ visibility (NMR K+/total tissue K+) of 96%, 62 +/- 8%, 47 +/- 1.9%, 45 +/- 3.5%, and 43 +/- 2.5% for blood, brain, muscle, kidney, and liver, respectively. Absolute tissue K+ was determined by flame photometry of acid-digested tissue. Changes in tissue K+ status by chronic K+ depletion or acute K+ loading produced changes of 39K NMR signal intensity that were equal to changes of absolute tissue K+. Acidosis, alkalosis, mannitol, or RbCl infusion did not significantly change the NMR K+ signal. These results indicate that the changes in K+ detected by NMR were specifically and accurately detected. To investigate the factors that affect the 39K NMR signal, the effects of liver homogenate on 39K NMR signal intensity were studied. Addition of homogenate produced a 60% loss of signal intensity, suggesting that a large portion of cell K+ may be only 40% visible. Addition of RbCl to undiluted homogenate increased the NMR K+ signal by 11 +/- 2 mumol/g. Addition of H2O or NaCl had no effect, suggesting that Rb+ was replacing K+ in sites of low (less than 40%) NMR visibility. These results demonstrate that 39K NMR experiments can be performed using intact organs. To explain the lack of detectable K+ and changes in K+ NMR visibility, a three compartment model is proposed.

Animals↗
PubMed1987

Localization and characterization of renal calcitonin receptors by in vitro autoradiography.

Calcitonin receptor binding sites were identified in renal cortex and medulla using the radioligand 125I-salmon calcitonin. Microscopic localization of these receptors revealed binding over medullary and cortical thick ascending limb of the loop of Henle and in distal convoluted tubule. A number of receptor positive cells in the inner medulla were also identified. Characterization of the binding demonstrated a single class of high-affinity binding sites in both the medulla and the cortex with affinity constants of 0.74 +/- 0.09 x 10(9) M-1 and 0.32 +/- 0.05 x 10(9) M-1, respectively, and receptor concentrations of 205 +/- 45 fmol/mg protein and 453 +/- 54 fmol/mg protein, respectively. Competition for 125I-salmon calcitonin binding by a wide range of calcitonin analogs revealed a close correspondence between the reported biological potencies and activities in the current system. The localization of binding sites within the nephron corresponds to the reported localization of calcitonin-stimulated adenylate cyclase activity and suggests that the receptor mediated actions of calcitonin in the kidney utilize cyclic AMP as a second messenger. In addition, the microscopic identification of specific calcitonin receptors helps the delineation of direct actions of this hormone from those which are indirect.

Animals↗
PubMed1987

Water depletion, not oral sodium loading, increases levels of sodium, potassium-dependent adenosine triphosphatase inhibitors in rat plasma.

In order to define a physiological role for circulating inhibitors of sodium, potassium-dependent adenosine triphosphatase (Na+,K+-ATPase), plasma was obtained from control, water deplete, water repleted, sodium deplete and sodium loaded rats. The effect of this plasma on Na+,K+-ATPase activity, and its transport equivalent 86Rb uptake, was measured in separated guinea pig renal cortical tubules. Plasma from water deplete rats had a raised plasma osmolality and sodium concentration and a significant inhibitory effect on Na+,K+-ATPase (14%) and 86Rb uptake (24%) compared with control or water repleted rats. Inhibition of Na+,K+-ATPase and 86Rb transport was not seen with plasma from rats after dietary sodium loading (urine sodium 5.2 +/- 0.9 mmol/day) compared with low sodium diet controls (urine sodium 0.41 +/- 0.08 mmol/day). Des-amino arginine vasopressin in vivo produced no inhibition of Na+,K+-ATPase or Rb transport. These studies suggest, that in terms of common homoeostatic insults, circulating inhibitors of Na+,K+-ATPase are more responsive to water depletion than to oral sodium loading. The inhibitors may fulfil a physiological role in increasing sodium excretion to maintain osmolality after dehydration.

Animals↗
PubMed1987

In vivo estimation of changes in distal tubule flow and their role in dexamethasone-induced kaliuresis in control and potassium-adapted rats.

The aim of this study was to determine whether the kaliuresis associated with glucocorticoids is due to a direct tubular action or is secondary to effects of glucocorticoids on distal tubule flow. A whole kidney technique was used to avoid the problem, inherent in microperfusion and micropuncture studies, of deciding whether (all) the appropriate nephron segment(s) are being studied. The method used was to determine the best whole kidney measure of distal tubule flow (the independent variable) by correlating this with the dependent variable (potassium excretion, corrected for differences in plasma potassium, UkV/PIK+) in conscious intact and adrenalectomized control and potassium-adapted rats. After an intragastric potassium chloride load, the correlation of UkV/PIK+ with UkV + UNaV was better than with either UNaV or UV, as measures of distal tubule flow. From the relationship a measure of potassium excretion independent of distal tubule flow can thus be calculated as UkV/PIK+ divided by (UkV + UNaV), defined as UK#. Measurement of UK# clearly demonstrates decreases in potassium excretion with adrenalectomy and increases in potassium excretion with aldosterone and in the potassium-adapted rat, consistent with described changes in potassium secretion. In contrast, with dexamethasone treatment, whilst there was an increase in UkV and UkV/PIK+, there was no change in UK# either in the control of potassium-adapted rats. These results suggest that the kaliuretic effect of dexamethasone cannot be attributed to direct tubular effects of glucocorticoids but rather can be explained by its effect on distal tubule flow.

Adaptation, Physiological↗
PubMed1987

Aldosterone is a physiologically significant kaliuretic hormone.

To study the role of aldosterone in the short-term control of potassium excretion, rats were gavaged with a liquid diet containing 10-20% of their daily caloric and potassium intake, with a range of sodium intakes. Levels of (effective) aldosterone at the time of gavage were manipulated by administration of spironolactone, aldosterone, and adrenalectomy. Urinary sodium, potassium, and creatinine excretion were measured in conscious unrestrained rats for 2 h after the food load, and then blood was collected for measurement of plasma potassium, aldosterone, and renin activity. Potassium excretion was dependent on both dietary potassium and a minimum dietary sodium content. Potassium excretion was reduced by spironolactone and adrenalectomy and increased by acute aldosterone treatment in most dietary groups. These results strongly suggest that the ambient levels of aldosterone are important in determining potassium excretion following food ingestion. Plasma aldosterone was higher with the higher potassium and lower sodium content diets. Changes in plasma aldosterone, with variations in dietary potassium or sodium, suggest a role for aldosterone in subsequent potassium excretion.

Adrenalectomy↗
PubMed1986

A simple method for definition of incomplete suppression of aldosterone and its association with hypertension and hypokalaemia in man.

By defining a model for control of potassium homoeostasis, patients with unexplained hypokalaemia may then be described as fitting or not fitting the model. Fitting the model implies an abnormality of known control mechanisms (e.g. aldosterone); by contrast, not fitting the model suggests other unknown factors responsible for the hypokalaemia and, possibly, hypertension. In the presence of normal acid-base status, potassium excretion (UK+V) is regulated by plasma potassium (PK+), delivery of sodium to the distal tubule and aldosterone secretion. A linear relationship (correlation coefficient of 0.72) was defined by: UK + V/PK+ = 5.1 X log(UAldoV) X log(UNa+ V) + 1.4 based on a 24 h urine collection and plasma sample, in 16 normal subjects, 50 hypertensive normokalaemic subjects and 11 patients with hyperaldosteronism. The relationship was robust and held true for variations in dietary sodium and potassium intake (5-300 and 20-100 mmol/day respectively) and variations in aldosterone excretion produced by enalapril. Patients with abnormal renal potassium wasting due to known extraneous factors (n = 11) all fell outside the 95% confidence limits. Twelve patients with hypertension and hypokalaemia and renal potassium wasting all fitted within the confidence limits, being no different from 22 controls selected on the basis of age and urinary potassium excretion (30-50 mmol/day). This suggests that in these 12 patients the hypokalaemia (but not necessarily the hypertension) was not due to 'unknown' steroids but rather lack of regulation of the controlling variable, aldosterone.

Aged↗
PubMed1986

Aromatic L-amino acid decarboxylase: histochemical localization in rat kidney and lack of effect of dietary potassium or sodium loading on enzyme distribution.

Utilizing a mono-specific antiserum produced in rabbits to hog kidney aromatic L-amino acid decarboxylase (AADC), the enzyme was localized in rat kidney by immunoperoxidase staining. AADC was located predominantly in the proximal convoluted tubules; there was also weak staining in the distal convoluted tubules and collecting ducts. An increase in dietary potassium or sodium intake produced no change in density or distribution of AADC staining in kidney. An assay of AADC enzyme activity showed no difference in cortex or medulla with chronic potassium loading. A change in distribution or activity of renal AADC does not explain the postulated dopaminergic modulation of renal function that occurs with potassium or sodium loading.

Animals↗
PubMed1986

31P-NMR in vivo measurement of renal intracellular pH: effects of acidosis and K+ depletion in rats.

Renal intracellular pH (pHi) was measured in vivo from the chemical shift (sigma) of inorganic phosphate (Pi), obtained by 31P-nuclear magnetic resonance spectroscopy (NMR). pH was calculated from the difference between sigma Pi and sigma alpha-ATP. Changes of sigma Pi closely correlated with changes of sigma monophosphoesters; this supports the hypothesis that the pH determined from sigma Pi represents pHi. Renal pH in control rats was 7.39 +/- 0.04 (n = 8). This is higher than pHi of muscle and brain in vivo, suggesting that renal Na-H antiporter activity raises renal pHi. To examine the relationship between renal pH and ammoniagenesis, rats were subjected to acute (less than 24 h) and chronic (4-7 days) metabolic acidosis, acute (20 min) and chronic (6-8 days) respiratory acidosis, and dietary potassium depletion (7-21 days). Acute metabolic and respiratory acidosis produced acidification of renal pHi. Chronic metabolic acidosis (arterial blood pH, 7.26 +/- 0.02) lowered renal pHi to 7.30 +/- 0.02, but chronic respiratory acidosis (arterial blood pH, 7.30 +/- 0.05) was not associated with renal acidosis (pH, 7.40 +/- 0.04). At a similar level of blood pH, pHi was higher in chronic metabolic acidosis than in acute metabolic acidosis, suggesting an adaptive process that raises pHi. Potassium depletion (arterial blood pH, 7.44 +/- 0.05) was associated with a marked renal acidosis (renal pH, 7.17 +/- 0.02). There was a direct relationship between renal pH and cardiac K+. Rapid partial repletion with KCl (1 mmol) significantly increased renal pHi from 7.14 +/- 0.03 to 7.31 +/- 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗
PubMed1986

Local actions of angiotensin II: quantitative in vitro autoradiographic localization of angiotensin II receptor binding and angiotensin converting enzyme in target tissues.

In order to gain insight into the local actions of angiotensin II (ANG II) we have determined the distribution of a component of the effector system for the peptide, the ANG II receptor, and that of an enzyme-catalysing ANG II formation, angiotensin converting enzyme (ACE), by in vitro autoradiography in several target tissues. The superagonist ANG II analog, 125I[Sar1]ANG II, or the antagonist analog, 125I[Sar1,Ile8]ANG II, were used as specific radioligands for ANG II receptors. A derivative of the specific ACE inhibitor, lysinopril, called 125I-351A, was used to label ACE in tissues. In the adrenal, a high density of ANG II receptors occurs in the glomerulosa zone of the cortex and in the medulla. ACE is also localized in these two zones, indicating that local production of ANG II may occur close to its sites of action in the zona glomerulosa and adrenal medulla. In the kidney, a high density of ANG II receptors is associated with glomeruli in the cortex and also with vasa recta bundles in the inner stripe of the outer medulla. ACE is found in very high concentration in deep proximal convoluted tubules of the cortex, while much lower concentrations of the enzyme occur in the vascular endothelium throughout the kidney. In the central nervous system three classes of relationships between ANG II receptors and ACE are observed: In the circumventricular organs, including the subfornical organ and organum vasculosum of the lamina terminalis, a high concentration of both components occurs. Since these structures have a deficient blood-brain barrier, local conversion of circulating angiotensin I (ANG I) to ANG II may contribute to the action of ANG II at these sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗
PubMed1985

Potassium excretion by the isolated perfused kidney from the potassium-adapted rat.

Adaptation to a high potassium diet leads to an enhanced ability to excrete an acute potassium load. The aim of this study was to examine whether the enhanced kaliuretic ability is an intrinsic renal adaptation or is secondary to extrarenal mediators such as aldosterone. Kidneys from control rats and rats on a high potassium diet were isolated and perfused in a cell-free medium (glomerular filtration rate 0.5 ml/min, fractional sodium reabsorption 95%). Feeding in the 24 h prior to perfusion had a profound effect on fractional K+ excretion in rats on high K+ (fed 1.4 +/- 0.11, fasted 0.70 +/- 0.07) but not in control (fed 0.59 +/- 0.05, fasted 0.64 +/- 0.05) rats. After feeding but not fasting, rats on high K+ had a greater fractional K+ excretion than control K+ rats. Spironolactone inhibited fractional K+ excretion in fed rats on high K+ but not in control rats (high K+ 1.45 +/- 0.18, high K+ + spironolactone 0.95 +/- 0.15; control 0.59 +/- 0.05, control + spironolactone 0.46 +/- 0.02). Although these experiments do not exclude an intrinsic renal adaptation in potassium excretion, a major component of the increased potassium excretion relates to the increased potassium intake, probably mediated via aldosterone.

Adaptation, Physiological↗
PubMed1985

Production and excretion of dopamine by the isolated perfused rat kidney.

Renal catecholamine concentrations and urinary dopamine excretion from the isolated perfused kidney were measured in intact and peripherally sympathectomized rats. Urinary dopamine excretion was not diminished by sympathectomy, was increased by l-dopa (but not tyrosine or dopamine 4-O-sulphate) in the perfusate and was virtually abolished by prior treatment with the dopa decarboxylase inhibitor, carbidopa. These results confirm the importance of renal extraneuronal dopamine production, from circulating l-dopa, as a contributor to urinary dopamine excretion.

Animals↗
PubMed1985

Magnetic resonance spectroscopy for evaluation of renal function.

In summary, MRS is a powerful tool for the noninvasive measurement of tissue metabolism and pH. 31P MRS measures high-energy phosphates and pH, 1H MRS measures carbon metabolism, and 14N detects nitrogenous compounds. Studies with perfused organs in experimental animals suggests that MRS has potential for noninvasive monitoring of the human kidney in health and disease. The production of large magnet systems which accommodate human subjects raises the possibility that MRS may be used for clinical diagnosis. There are several problems concerning the application of this technology to the investigation of human renal metabolism. Nevertheless, because this field is advancing so rapidly, it can be expected that within the next few years MRS will be used to study human kidneys in health and disease. Whether or not MRS proves to be a useful diagnostic tool in clinical medicine remains to be determined.

Acute Kidney Injury↗
PubMed1984

Vasculitis and glomerulonephritis: a subgroup with an antineutrophil cytoplasmic antibody.

Four subjects whose plasma produced positive staining of neutrophil cytoplasm, on testing for antinuclear factor, have been found over eight years (and over 10,000 antinuclear factor studies). All four had evidence of diffuse systemic disease with polyarthralgia and lung involvement. Three of four (at least) had evidence of renal involvement and two of four skin biopsy evidence of vasculitis. Defining such a subgroup may help in defining etiology(s) and treatment regimes in diffuse vasculitic disease.

Antibodies, Antinuclear↗
PubMed1984

Renal potassium adaptation in the rat: role of glucocorticoids and aldosterone.

This study examines the role of adrenocortical hormones in the kaliuresis following an acute intragastric KCl load in conscious control (CK) and high potassium diet (HK) rats. Adrenalectomy, 1 day before test, reduced K+ excretion by 35% in CK and 60% in HK rats, leading to minimal differences in K excretion between CK and HK. By contrast, spironolactone inhibited K excretion by only 10%. Glucocorticoids (dexamethasone 3-10 micrograms/100 g) increased K+ excretion in adrenalectomized CK and to a greater extent in adrenalectomized HK rats. Aldosterone (3 micrograms/100 g) alone had a variable effect on urinary potassium excretion in adrenalectomized rats. A combination of dexamethasone (3 micrograms/100 g) and aldosterone (3 micrograms/100 g) in adrenalectomized rats induced potassium excretion equivalent to that in intact rats. Adrenalectomized HK rats had a greater kaliuretic response to dexamethasone and aldosterone than CK rats. These results 1) demonstrate a role for glucocorticoids in K+ excretion in HK rats and 2) illustrate the importance of the increased responsiveness to both glucocorticoids and mineralocorticoids in potassium adaptation.

Adaptation, Physiological↗