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Biomedical subjects

J G Ledingham

Publications and source records attributed to J G Ledingham.

At least 73 records · Page 4Linked to original sources
PubMed1987

Effects of aging on vasopressin secretion, water excretion, and thirst in man.

Disorders of water balance are common among elderly patients. A number of factors may contribute. Osmoreceptor-mediated release of AVP is increased, but the response to volume stimuli may be reduced. The capacity of the kidney to concentrate urine is reduced by age, but this impairment cannot be correlated with coincident loss of glomerular filtration (GFR); there may rather be a failure of cAMP response to AVP in aging kidneys. Free water clearance is reduced in the old in proportion to the loss of GFR. Thirst mechanisms are also significantly impaired in healthy as well as sick old people. This combination of factors renders old people particularly liable to develop disorders of water homeostasis during episodes of acute or chronic ill health.

Aging↗
PubMed1986

Acute renal failure in hemorrhagic hypotension: cellular energetics and renal function.

In male Wistar rats, renal adenosine triphosphate (ATP), inorganic phosphate (Pi) and intracellular pH were measured by 31phosphorus nuclear magnetic resonance (31P NMR) and correlated with renal function before, during, and for one hour after a period of 30 to 40 minutes hemorrhagic hypotension. In animals which suffered no change in these metabolites during hypotension, retransfusion immediately restored normal renal function. When metabolite changes were observed during hypotension, they occurred suddenly with severe ATP depletion, Pi accumulation, and intracellular acidosis occurring almost concurrently. Metabolic changes of this magnitude were always associated with renal dysfunction in the post-hypotensive period, which occurred even when the period of biochemical change was only 10 to 15 minutes. The abnormalities in post-hypotensive renal function resemble the pattern of change seen in human acute tubular necrosis (ATN): depressed glomerular filtration rate (GFR), urine output varying from polyuria to oliguria, decreased urine to plasma inulin ratio, increased urinary sodium concentration, increased fractional excretion of sodium, and increased fractional excretion of potassium. It is postulated that changes in renal cellular energy status during hemorrhagic hypotension distinguish pre-renal failure from early or incipient ATN.

Acute Kidney Injury↗
PubMed1986

Tubular reabsorption rates for myoglobin in the isolated perfused rat kidney.

The renal handling of myoglobin has been studied in the isolated perfused rat kidney. Myoglobin was freely filtered. Reabsorption by the renal tubules showed saturation kinetics with a relatively low maximum rate of reabsorption (Tmax) of 27-30 micrograms min-1 g-1 wet wt. at a perfusate concentration of 70-80 micrograms/ml. Myoglobin reabsorption is therefore much less than that reported for immunoglobulin light chain or lysozyme in this model. Large increases in sodium and water excretion produced by omission of oncotic agent from the perfusate did not alter the kinetics of myoglobin reabsorption. The use of bovine serum albumin as oncotic agent in the perfusate prevented the tubular reabsorption of myoglobin. Small amounts of albumin are filtered by the isolated perfused kidney and it is postulated that this albumin interferes with tubular reabsorption of myoglobin.

Absorption↗
PubMed1985

Neuropeptide Y: a novel renal peptide with vasoconstrictor and natriuretic activity.

A novel vasoconstrictor peptide, neuropeptide Y (NPY), has been identified in considerable quantities in the renal artery and kidney. Within the kidney, NPY was confined to the cortex and corticomedullary interface, the regions where the juxtaglomerular apparatus is most numerous. In the isolated perfused rat kidney, NPY caused a prompt dose-dependent increase in perfusion pressure and reduction in flow, with only a small fall in glomerular filtration rate (GFR). In spite of the reduced renal perfusion, a dose-dependent natriuresis was observed. This response contrasts to the response of this preparation to noradrenaline, which causes sodium reabsorption. The presence of a potent vasoconstrictor and natriuretic peptide within the rat renovascular system suggests that it may play a significant role in the control of renal function.

Animals↗
PubMed1985

Angiotensin II-induced thirst and vasopressin release in man.

1. The thirst and plasma vasopressin responses to single-blind controlled intravenous angiotensin II infusions (2-16 ng min-1 kg-1) were investigated in ten healthy young men. 2. Thirst and vasopressin secretion were stimulated in four out of ten subjects. These effects occurred at plasma angiotensin concentrations well above those measured under physiological conditions associated with thirst and vasopressin secretion such as water deprivation. 3. Further studies are needed to define why only certain individuals respond to intravenous angiotensin II infusions and to determine whether potentiation of angiotensin-induced thirst and vasopressin secretion by other stimuli (e.g. hypovolaemia and hypertonicity) might occur in man, in particular under pathological conditions when plasma angiotensin levels are above the physiological range.

Adult↗
PubMed1985

Osmotic thirst and vasopressin release in humans: a double-blind crossover study.

Thirst is a subjective sensation. Therefore to investigate further the nature, intensity, and specificity of osmotic thirst, we studied the effects of double-blind infusions of hypertonic (0.45 M) and isotonic (0.15 M) saline on subjective ratings and sensations of thirst, water intake, plasma vasopressin, and body fluids in seven healthy volunteer young men. Only the hypertonic saline significantly increased plasma sodium concentration, plasma osmolality, plasma vasopressin concentration, and visual analog ratings of thirst sensations. Both infusions expanded blood volume, which was greater with the hypertonic saline infusion. Neither solution significantly altered mean arterial blood pressure nor plasma angiotensin levels. Throughout a 60-min drinking period after the infusions, water intake was always significantly greater after the hypertonic saline than after the isotonic saline. The subjects described the thirst sensations as mainly due to a dry unpleasant tasting mouth, which was promptly relieved by drinking. Visual analog rating changes confirmed the subjective reports. Finally, the effects on thirst and vasopressin secretion were observed at plasma sodium concentration and osmolality changes that are well within the physiological range.

Adult↗
PubMed1985

Enalapril in the treatment of hypertension associated with impaired renal function.

This pilot study was undertaken to examine the safety and efficacy of enalapril in the treatment of hypertension associated with impaired renal function. Forty-one patients with glomerular filtration rate (GFR) < or = 50 ml/min received enalapril for up 12 weeks. Blood pressure, renal function, biochemistry and haematology were monitored weekly for 4 weeks and then monthly. Blood pressure was effectively reduced within 4 weeks; this reduction was maintained for at least 12 weeks. Renal function remained stable and there was no significant sustained alteration in any biochemical or haematological parameter. Requirement for additional antihypertensive drugs was reduced during enalapril therapy. These data suggest that enalapril may have a useful role in the management of hypertension associated with renal impairment.

Adult↗
PubMed1985

Early assessment of organ involvement in hypertension: renal assessment.

Hypertension in the malignant phase is all too commonly associated with impairment of renal function, which may be gross and dominate the clinical picture. In contrast, the vast majority of patients with essential hypertension show no evidence of impairment of renal function, despite the well recognized morbid anatomical changes of Renal haemodynamic changes can be detected in some two-thirds of hypertensive subjects with a variable decrease in renal blood flow and increase in filtration fraction. This pattern could be considered a potential mechanism for hyperfiltration damage to glomeruli, but there is no direct evidence. Estimates of renal blood flow and glomerular filtration rate are not sensitive indices of early renal damage of hypertensive origin. Much more sensitive but relatively unexplored is the measurement of micro-albuminuria in hypertensive patients. There is some evidence that the degree of micro-albuminuria may correlate inversely with the control of arterial pressure in essential hypertension. These observations and the suggestion that increased urinary N-acetyl-beta-D-glucosaminidase may be a sensitive index of renal tubular damage need further confirmation.

Acetylglucosaminidase↗
PubMed1984

Reduced thirst after water deprivation in healthy elderly men.

To determine whether responses to dehydration are altered with age, we investigated the thirst, fluid and electrolyte responses, and hormonal responses to 24 hours of water deprivation in seven healthy active elderly men (67 to 75 years old) and seven healthy young men (20 to 31 years old) who were matched for weight loss during water deprivation. After water deprivation, the older men had greater increases in plasma osmolality, sodium concentration, and vasopressin levels. However, their urinary osmolality was lower and they were less thirsty and drank less after water deprivation, so that their plasma and urine were not diluted to predeprivation levels. Regression analysis indicated increased sensitivity of vasopressin osmoreceptors in the older group, although this difference was not statistically significant. We conclude that after 24 hours of water deprivation, there is a deficit in thirst and water intake in healthy elderly men, as compared with younger men, although vasopressin osmoreceptor responsiveness is maintained or even increased. Our findings also suggest that the well-known deficit in urinary concentrating ability that occurs with age reflects renal causes and not a lack of circulating vasopressin.

Adult↗
PubMed1984

Changes in cerebral blood flow in patients with severe congestive cardiac failure before and after captopril treatment.

The intravenous 133xenon injection method was used to estimate global cerebral blood flow before and after treatment with captopril in nine patients with severe heart failure. The pretreatment mean blood pressure was 94.9 mm Hg (S.D. 13.9) and fell to 85.1 mm Hg (S.D. 18.1) after treatment with captopril for between four and 15 days. The cerebral blood flow before captopril was 61.1 ml/100 g per minute (S.D. 6.9), which was less than the value of 75.8 ml/100 g per minute found in control subjects. After treatment with captopril the cerebral blood flow increased to 73.8 ml/100 g per minute (S.D. 11.8, p less than 0.01). The fraction of carbon dioxide in the expired air was not significantly different in the two studies (4.1 +/- 0.88 versus 3.97 +/- 0.65). It is concluded that cerebral blood flow is reduced in severe heart failure and can be restored by treatment with captopril, but the reasons for the reduced flow and its improvement after converting enzyme inhibition are not known.

Adult↗
PubMed1984

Body fluid changes, thirst and drinking in man during free access to water.

To investigate whether human thirst and drinking during ad lib access to water occur in response to body fluid deficits, we obtained blood samples and visual analog scale thirst ratings from five healthy, volunteer, young men at hourly intervals and when they were thirsty during a normal working day. Although there were significant increases in ratings of thirst, pleasantness of drinking water, mouth dryness and unpleasantness of the taste in the mouth when subjects were thirsty enough to drink compared with intervening intervals, there were no concomitant changes in body fluid variables (microhematocrit, plasma osmolality and plasma sodium, potassium, protein and angiotensin II concentrations). Subjects drank mainly in association with eating and were not overhydrated as indicated by constantly hypertonic urine and significant tubular reabsorption of free water over the experimental period. The results indicate that during free access to water humans become thirsty and drink before body fluid deficits develop, perhaps in response to subtle oropharyngeal cues, and so provide evidence for anticipatory thirst and drinking in man.

Adult↗
PubMed1984

Significance of intraocular pressure measurement in systemic hypertension.

In normotensive subjects no differences were found between morning and afternoon measurements of (i) mean level of intraocular pressure (IOP), (ii) variance of IOP, and (iii) rise of IOP associated with lying down. Conversely, in subjects with untreated hypertension ( UH ) morning values of (i), (ii), and (iii) were all significantly elevated. Within each group morning and afternoon levels of systolic blood pressure (BP) remained constant but in UH the morning variance of systolic BP was elevated in proportion to the degree of hypertension. This disparate elevation resulted in highly significant correlations between levels and variance of systolic BP and IOP in the morning. These correlations were weaker or absent in the afternoon, and in normotensive persons at both times. These observations may explain the tendency of retinal vein occlusion to occur in the morning. Their relationship to the vascular changes of hypertension pose a problem for future study.

Adult↗