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Biomedical subjects

J D Slater

Publications and source records attributed to J D Slater.

At least 109 records · Page 6Linked to original sources
PubMed1982

Renin and aldosterone at high altitude in man.

Measurements have been made of hormonal changes relevant to salt and water balance during prolonged exposure to hypoxia to improve our understanding of the syndrome of acute mountain sickness. We have attempted to delineate the detailed inter-relationships between the renin-aldosterone and the vasopressin systems by a metabolically controlled study, involving an orthostatic stress (45 degrees head-up tilt) and an injection of a standard dose of ACTH to test adrenal responsiveness. Three Caucasian medical students underwent a 7-day equilibration at 150 m (Lima, Peru), followed by a 6-day sojourn at 4350 m (Cerro de Pasco, Peru) and a final 7 days at 150 m. Measurements were made of sodium and potassium balance, body weight and the 24-h renal excretion of vasopressin, cortisol and aldosterone 18-glucuronide. These variables showed little change, except for that of aldosterone 18-glucuronide, which fell sharply at altitude and rebounded even more sharply on return to sea level. At altitude, basal plasma levels of renin activity and aldosterone fell, and the response to orthostasis was attenuated, but the fall of plasma renin activity, as compared to plasma aldosterone, was delayed; on return to sea level this dissociation was exacerbated with the return of normal renin responsiveness lagging behind that of aldosterone. We suggest that unknown factors which dissociate the orthodox renin-aldosterone relationship, other than the activity of the angiotensin I-converting enzyme, are operative on exposure to hypoxia.

Adult↗
PubMed1981

Kinetic and isotope effect studies of maize phosphoenolpyruvate carboxylase.

Carbon isotope effects for the carbon atom arising from bicarbonate have been measured for the phosphoenolpyruvate carboxylase from maize. At pH 7.5, 25 degrees C, the isotope effect is K12/k13 = 1.0029 +/- 0.0005 in the presence of Mg2+. The isotope effect decreases with increasing pH, reaching a value of 0.9973 at pH 10.0. All these isotope effects are relative to HCO3(-) taken as the starting state. If CO2 is considered the starting state, the isotope effects are all inverse. These values suggest that the carboxylation of phosphoenolpyruvate occurs by way of a stepwise mechanism involving an enzyme-bound carboxyphosphate intermediate, with formation of the intermediate being the primary rate-determining step. Steady-state kinetics reveal that Vmax is independent of pH over the range pH 7.5-10.0 Vmax/Km (phosphoenolpyruvate) is bell shaped in the same interval. Two pKa values near 7 are observed; the first is attributed to ionization of the phosphate group of phosphoenolpyruvate and the second to an unidentified group on the enzyme. Activity of the enzyme also depends on protonation of a group on the enzyme with a pKa near 10. Several metal ions were tested as activators of phosphoenolpyruvate carboxylase. Under saturating conditions, Mg2+ and Mn2+ show equal activity but different carbon isotope effects. Co2+ has about half the activity of Mg2+ and shows an inverse carbon isotope effect.

Bicarbonates↗
PubMed1981

A radioimmunoassay for the measurement of tetrahydroaldosterone 3-glucosiduronic acid in human plasma.

A simple, reliable and specific radioimmunoassay procedure for the measurement of the principal aldosterone metabolite, tetrahydroaldosterone 3-glucosiduronic acid, in human plasma is described. The glucosiduronate is extracted from plasma (generally 200 microliter) by the use of Amberlite XAD-2 resin, eluted with acidic, aqueous ethanol, separated from unconjugated steroids by partition and estimated using a specific antibody. A disequilibrium system is used, but with a conventional charcoal separation; the advantages of such a system are discussed. Data obtained by incorporating chromatographic separations into the assay procedure is presented as evidence for the specificity of the method. Data concerning the long-term storage of plasma samples is given, together with plasma concentrations of the glucosiduronate in both normal people and in people with abnormalities of aldosterone secretion.

Aldosterone↗
PubMed1981

The diagnosis of primary hyperaldosteronism.

An aldosterone-suppression test based on a simple method of extracellular-fluid volume expansion over three days reliably discriminated between patients with aldosterone-producing adenomas, idiopathic adrenal hyperplasia, and essential benign hypertension. In patients with primary hyperaldosteronism adrenal-vein plasma aldosterone/cortisol concentration ratios successfully lateralised all 21 adenomas. In patients with an adenoma the contralateral adrenal gland was always suppressed, as indicated by a ratio which was less than that seen in the lower inferior vena cava, whereas in patients with hyperplasia the adrenal-vein aldosterone/cortisol concentration ratio from each adrenal was always greater than that seen in the lower inferior vena cava. Thus adrenal-vein sampling not only lateralises solitary adenomas but also discriminates between patients with an adenoma or hyperplasia. However, in view of the diagnostic reliability of the suppression test, it is suggested that adrenal-vein sampling is unnecessary in hyperaldosteronism due to adrenal hyperplasia.

Adenoma↗
PubMed1981

Factors relating to aldosterone secretion rate, the excretions of aldosterone 18-glucuronide, and the plasma aldosterone concentration in cirrhosis.

In a group of eight patients with cirrhosis the rate of renal excretion of the 18-glucuronide metabolite of aldosterone (U Aldo V) was found to be closely related to the aldosterone secretion rate (ASR). U Aldo V was therefore used as an index of ASR in a further group of fifty patients in order to evaluate the possible importance of factors known to regulate aldosterone secretion. U Aldo V showed statistically significant relationships to both plasma renin activity (PRA) and the plasma sodium concentration (P Na), but not to the plasma potassium concentration (PK) or the renal excretion of cortisol (U Cort V), the latter sued as an index of adrencorticotrophic hormone activity. The plasma aldosterone concentration (P Aldo) was determined in fifty-eight patients and also found to show statistically significant relationships to PRA and P Na. P Aldo showed a weak, though statistically significant, relationship to PK, but not to U Cort V. These findings are in keeping with a role for the renin-angiotensin system in the control of aldosterone secretion in cirrhosis although evidence from other studies suggest other factors to be involved also. Whether P Na was another determinant of ASR, or whether aldosterone was a determinant of P Na through regulating sodium reabsorption by the proximal tubule of the nephron, is uncertain.

Adult↗
PubMed1980

The cardiovascular effect of vasopressin in relation to its plasma concentration in man and its relevance to high blood pressure.

The cardiovascular response and the changes of plasma arginine vasopressin (AVP) concentration following graded doses of AVP infused intravenously have been defined in six normal young men. The same measurements were also made during fluid deprivation in a patient with both nephrogenic diabetes insipidus and systemic hypertension. When, following AVP infusion, mean diastolic arterial pressure increased from 72 +/- 3 mmHg (SEM) to 78 +/- 2 mmHg (SEM) in the normal subject group, mean plasma AVP increased by 14.5 fmol/ml. When the patient was deprived of water, diastolic pressure increased, despite the fluid loss, from 90 to 105 mmHg, with a comparable increase of plasma AVP concentration of 15.3 fmol/ml. Further increases of plasma AVP concentration in either the normal subjects or in the patient were not associated with further increments of arterial pressure. We suggest that under pathophysiological circumstances in man plasma AVP concentrations may achieve levels which have a significant cardiovascular effect.

Adult↗
PubMed1979

Renal sodium retention in cirrhosis: relation to aldosterone and nephron site.

1. In a group of patients with cirrhosis who showed a wide range of values for the rate of renal sodium excretion, the latter was found to be inversely related to both the plasma concentration and rate of renal excretion of aldosterone. However, for a given sodium excretion the values for aldosterone were significantly lower in the patients than for a group of healthy control subjects. These findings suggest either an increased renal tubular sensitivity to aldosterone or the participation of other factors in the pathogenesis of the sodium retention. 2. Based on measurements of the rate of urine flow and the clearances of free water and inulin during a maximal water diuresis, the fractional reabsorption of sodium by the 'proximal', 'diluting segment' and 'distal' segments of the nephron was estimated. For patients retaining sodium the enhanced reabsorption occurred at both proximal and distal sites, the latter being quantitatively more important. There was no significantly enhanced sodium reabsorption in the diluting segment.

Aldosterone↗
PubMed1978

Effect of arterial pressure and inheritance on the sodium excretory capacity of normal young men.

1. In normal young adult sons of normotensive parents the rate of renal sodium excretion is highly correlated with mean arterial pressure after a large intravenous isotonic fluid load. The correlation appeared to strengthen with time and was improved when the rate of sodium excretion was corrected for variations in the rate of glomerular filtration. 2. There was no such correlation in normal, age-matched sons of hypertensive parents. 3. In eight of the 20 normotensive sons of hypertensive parents studied, the rate of renal sodium excretion per unit of mean arterial pressure was significantly higher than in the sons of normotensive parents. 4. Because the sons of hypertensive parents are much more likely to become hypertensive than those of normotensive parents, we suggest that an abnormality of renal sodium handling precedes the development of demonstrable hypertension.

Adolescent↗
PubMed1978

The inhibiton of adrenergically provoked renin release by salbutamol in man.

1 The beta-adrenoceptor agonist salbutamol is shown to have antagonist properties by its effect on adrenergically provoked renin release in normal people. 2 It significantly reduces the rate of renin secretion provoked by either endogenous (85 dregrees head-up tilt) or exogenous (isoprenaline infusion) adrenergic stimulation. 3 Because renin is relatively simple to measure, and because in acute studies its release is relatively uninfluenced by the vagaries of direct and reflex cardiovascular effects, we suggest that, in the characterization of drugs which act on adrenergic beta-receptors, an assessment of their effects on renin release would be useful.

Adult↗
PubMed1978

Radioimmunoassay of arginine-vasopressin in human urine and its use in physiological and pathological states.

A highly specific radioimmunoassay for arginine-vasopressin (AVP) in human urine has been developed, with a detection limit of 2.2 fmol/ml. The mean recovery of added AVP was 99.5 +/- 3.1 (S.D.)% when correction was made for the fact that an inverse relationship was observed between the recovery of AVP and the osmolality of the urine. The intra- and interassay coefficients of variation were 3.5--7 and 2.5--10% respectively. Arginine-vasopressin remains stable in urine after repeated freezing and thawing after storage at 4 or 20 degrees C for up to 7 days and at -20 degrees C for more than 3 months. During unrestricted fluid intake in normal people, the mean rate of renal excretion of AVP was 95 +/- 68 (S.D.) fmol/min. An isosmotic reduction of 9% in the plasma volume increased the excretion of AVP to 259 +/- 147 (S.D.) fmol/min. At the height of water-induced diuresis the rate of excretion fell to 70 +/- 28 (S.D.) fmol/min. Fluid deprivation for 18 h produced a moderate but significant increase in mean excretion of AVP, to a value of 116 +/- 67 (S.D.) fmol/min. Patients with compulsive water drinking showed a normal relationship between urine osmolality and the rate of excretion of AVP. In pituitary diabetes insipidus, AVP was undetectable, whereas in hereditary nephrogenic diabetes insipidus a progressive increase in the rate of excretion of AVP was observed in response to dehydration. There was a wide variation in the rate of excretion of AVP (range 126--8704 fmol/min) in patients with unexplained hyponatraemia, presumed to be due to an inappropriate secretion of antidiuretic hormone. Despite this variation, the relationship between urine osmolality and the rate of excretion of AVP clearly differed from that observed in normal people.

Adult↗
PubMed1977

Development of radioimmunoassays for the measurement of aldosterone in unprocessed plasma and simple plasma extracts.

Inexpensive and rapid radioimmunoassay techniques for the measurement of aldosterone in unprocessed plasma and simple plasma extracts are described. The use of low pH (pH 5.0) and merthiolate to minimise plasma protein binding and the use of aldosterone-free plasma in the standards allows the measurement of aldosterone in 50 microliter of unprocessed plasma, which has been found useful in the diagnostic screening and classification of hyperaldosteronism. Despite quantitative recovery of added (+)-aldosterone and high specificity, the aldosterone content of unprocessed plasma is overestimated, probably by the presence of a water-soluble compound which closely resembles aldosterone. The use of a simple preliminary dichloromethane extraction procedure gives an excellent correlation with values obtained after chromatography. Values are given for chosen normal people and people with benign essential hypertension, using both assay procedures in three different physiological contexts.

Aldosterone↗
PubMed1977

The kidney and aldosterone in acclimatization at altitude.

Five climbers were studied during an ascent of a 7500 m mountain in the Hindu Kush. Representiative samples from 24-hour urines were preserved from five subjects at 5400 m and 6600 m and from two at 7000 m. Sodium and cortisol excretion was normal, but that of potassium and especially aldosterone was low, especially in two climbers who had episodes of peripheral oedema. Hypoaldosteronism is a feature of high altitude acclimatization but its cause and significance have still to be elucidated.

Acclimatization↗
PubMed1977

Vasovagal hypotension and vasopressin release.

Mild vasovagal hypotension occurred in two normal male volunteers during insertion of indwelling venous cannulae. In spite of a rapid intravenous fluid load (3.6-4.6 litres in 90 min) both subjects passed little urine for 100 min. When the experiment was repeated without vasovagal hypotension, a rapid large diuresis followed the fluid load. The prolonged oliguria after vasovagal hypotension was the result of vasopressin release. This was demonstrated by measuring vasopressin in the blood and urine and by observing the renal response to a water load. The observation in man that a mild transient hypotensive episode may reduce urine flow for 100 min has clinical significance.

Catheterization↗
PubMed1977

The effect of isoprenaline on plasma renin activity in man: a dose-response curve.

Four normal subjects on a free sodium intake received intravenous isoprenaline in doses of 2, 4, 8 and 16 microgram over 2 min. Three of the subjects received a second infusion of 8 microgram. The rate of renin release indexed by changes in plasma renin activity increased in all subjects at each dose level. The mean peak levels of plasma renin were 9%, 29% and 77% above the mean control levels at doses of 2, 4 and 8 microgram respectively. The response of 16 microgram was no different from that seen with 8 microgram. The renin response obtained at 8 microgram was highly reproducible such that the coefficient of variation for duplicate estimations of plasma renin (twelve duplicates) ranged from 1.7 to 4%.

Dose-Response Relationship, Drug↗