PubMed Health⌕ Search

Biomedical subjects

J M Ledingham

Publications and source records attributed to J M Ledingham.

At least 37 records · Page 2Linked to original sources
PubMed1990

Salt appetite, body sodium, handling of a NaCl load, renin, and aldosterone in genetically and spontaneously hypertensive rats.

Salt appetite, body sodium, handling of a NaCl load, plasma renin activity (PRA), and plasma aldosterone concentration (PAC) were compared in New Zealand genetically hypertensive (GH) and Japanese spontaneously hypertensive rats (SHRs) and their respective normotensive controls [normal Wistar (N) and Wistar-Kyoto (WKY) rats]. Salt appetite was increased in SHRs compared with GH, N, and WKY rats when rats were on salt-free chow and given a choice of distilled water and NaCl solution. Body sodium, measured by whole body counting, was higher in SHRs than in the other strains but did not differ among GH, N, and WKY rats. The rate of excretion of a NaCl load was not increased in GH rats and was slightly increased in SHRs only when on a very low NaCl intake. PRA and PAC (radioimmunoassay) were lower in SHRs than in GH, N, and WKY rats. PAC had a significant negative correlation with body sodium across the four strains. There is no evidence of any abnormality in sodium regulation in GH rats. However, the SHRs have an increased salt appetite and an increased body sodium even when sodium intake is limited; PRA and PAC appear to have responded appropriately to the increased body sodium.

Aldosterone↗
PubMed1989

Effect of enalapril on handling of a sodium chloride load by genetically hypertensive and normotensive rats.

1. Enalapril was given in the drinking water (300 mg/L) for 4.5 days to normotensive (N) and genetically hypertensive (GH) rats on zero sodium intake. An intraperitoneal NaCl load was given 12 h after enalapril was started. 2. Enalapril did not increase the maximum rate of sodium excretion, but caused the rats to excrete more than the load in the first 24 h and then to have a slow fall in body sodium while on a sodium-free diet. 3. In terms of the Strauss et al. (1958) concept of body sodium, enalapril appears to lower the basal level. However, in addition it causes a slow leak of sodium which becomes apparent when sodium intake is very low.

Animals↗
PubMed1989

Autoregulation in hypertension: a review.

The hypothesis examined here is that autoregulation of peripheral flow is the dominant factor in initiating and maintaining the rise in peripheral resistance in hypertension. Vascular smooth muscle possesses myogenic activity, which is dependent upon wall tension and thus upon intravascular pressure, but the activity is modulated by metabolic factors which are flow-dependent. Autoregulation of flow by the microvessels is considered to be a reflection of the wider concept of autoregulation of tissue or cellular oxygen tension through the control of oxygen delivery and extraction in relation to oxygen consumption. Indirect evidence for the hypothesis, involving the measurement of oxygen delivery and consumption both in the whole body and in defined regions in various forms of hypertension, is discussed. Individual and species differences in the type of response of the microvessels to changes in oxygen tension and in the dependence/independence of oxygen consumption on flow may account for some of the discrepant observations. Specific criticisms of the hypothesis are discussed and it is concluded that the balance of indirect evidence supports the hypothesis. Lastly, if autoregulation is indeed involved in development of hypertension, it constitutes only a part of a complex pathogenic mechanism, whose major role is to maintain sodium and water balance in the body.

Animals↗
PubMed1987

Handling of a sodium load by rats on a low sodium intake and frusemide.

1. Groups of rats (n = 9-10 per group) were given a medium sodium (Na) diet or a low Na diet or a low Na diet plus low or high dose frusemide in order to have their body Na in a state of surplus or deficit or neither. 2. Body Na was measured by a 22Na whole body counting method involving Na-free chow and the drinking fluid as the only source of Na (22Na-labelled NaCl). Intraperitoneal NaCl (same specific activity) loads were given and their excretion was measured by repeated measurements of body Na over the next 48 h. 3. Rats in surplus excreted more than the load; those in neither surplus nor deficit excreted more or less exactly the load (allowing for growth); those with a small deficit retained enough Na to make up most of the deficit; those with a deficit that was larger than the load retained approximately the whole load. 4. The results support the Strauss-Hollenberg concept that there is a basal body Na above which Na is excreted and below which any available Na is retained.

Animals↗
PubMed1986

Body sodium in rats: response to DOCA, adrenalectomy, changes in salt intake, and a salt load.

Body Na was studied by an isotope method in rats on Na-free diet plus a choice of H2O and 0.5% or 0.1% NaCl. Two groups (1 on 0.5%, 1 on 0.1% NaCl) had Silastic deoxycorticosterone acetate (DOCA) implants, two similar groups were sham operated, and a fifth group (on 0.5% NaCl) underwent adrenalectomy (ADX). Saline consumption increased in DOCA-treated and ADX rats. Body Na was increased by DOCA and by drinking 0.5% NaCl compared with 0.1% NaCl. Body Na after intraperitoneal NaCl loading (which raised body Na 8-10%) and withdrawal of NaCl drinking fluids was analyzed by use of the model y = Ae-a(t-d) + Be-bt, where y is body Na at time t and d is delay before fast rate constant a is established; d was greater on the lower Na intake. Rate constant a was not reduced by chronic DOCA treatment. Coefficient B of the slow exponential, representing the basal level to which body Na falls on zero Na intake, and equivalent to Hollenberg's "set-point," was higher in DOCA-treated rats. This analysis makes use of Hollenberg's set-point concept, but the findings suggest that the set-point is related to mineralocorticoid activity and is thus presumably variable.

Adrenalectomy↗
PubMed1985

Jan Brod.

Explore the source record for details and available documents.

Czechoslovakia↗
PubMed1985

Effects of DOCA and salt intake on body sodium, fluid intake, blood pressure and excretion of a sodium load in rats.

Body sodium was measured repeatedly by a whole-body counting method (22Na) in control and deoxycorticosterone acetate (DOCA)-treated Wistar rats taking a sodium-free pelleted diet and drinking a choice of H2O and either 0.5% NaCl or 0.1% NaCl (n = 11 per group, four groups). Body sodium was higher in DOCA-treated than in control rats and higher in rats on 0.5% NaCl than in those on 0.1% NaCl. These differences persisted even when all sodium intake was stopped. An intraperitoneal NaCl load was excreted at least as rapidly by the DOCA-treated as by the control rats. Commencement of excretion was slower in the rats on 0.1% NaCl than in those on 0.5% NaCl. It is concluded that DOCA raises the basal level of body sodium but does not slow down the excretion of sodium in the body in excess of the basal level.

Animals↗
PubMed1984

The relationship between oxygen delivery and consumption in the conscious rat before and after expansion of body fluid volumes.

Oxygen consumption and delivery (defined as the product of cardiac output, haemoglobin concentration and arterial oxygen saturation) and haemodynamic variables were examined in the conscious resting rat throughout the day and after the expansion of body fluid volumes. Cardiac output was measured in arbitrary units by electromagnetic flowmetry and oxygen consumption by respirometry. The variability of blood pressure in the basal state was significantly less than that of cardiac output. Oxygen consumption was significantly correlated with cardiac output and oxygen delivery. In studies undertaken throughout the day, both oxygen consumption and delivery fell in the afternoon and there was evidence that the relationship between these two variables was curvi- rather than recti-linear. During oral sodium chloride administration for 7 days, blood pressure rose and some evidence was found for an alteration in the relationship between oxygen consumption and delivery, with an excess of delivery relative to consumption, particularly on the first day of salt loading. Intravenous injection of sodium chloride solution (0.171 mol/l) did not alter the relationship between oxygen consumption and delivery. Expansion of blood volume, while the packed cell volume was maintained nearly constant, raised oxygen delivery transiently and evidence was obtained that the relationship between oxygen consumption and delivery was altered, with oxygen delivery rising relatively more than oxygen consumption. The findings are discussed in relation to the autoregulatory hypothesis of circulatory control and for the role of autoregulation in hypertensive states. The importance of relating oxygen delivery to metabolic requirements in studies of the role of autoregulation is emphasized.

Animals↗
PubMed1984

Handling of a salt load by hypertensive and normotensive rats on normal and low intakes of sodium.

The handling of an intraperitoneal salt (NaCl) load (about 10% of body Na) was studied by means of a whole-body counting method using 22Na in four strains of rat: spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto rats (WKY), New Zealand genetically hypertensive rats (GH), and outbred normotensive rats (N). The rats had previously been equilibrated so that their body Na was of the same specific activity as the injected NaCl. The load was given first at 10 weeks of age, while the rats had a choice of water and 0.5% NaCl to drink, and again at 13 weeks when the rats had a choice of water and 0.04% NaCl. All the strains excreted the load more slowly when on the low Na intake. The SHR excreted the load most quickly and the WKY most slowly. There was no difference between the GH and N rats in this respect. The SHR differed from the other strains in having an increased appetite for salt and an increased total body sodium relative to body weight.

Animals↗
PubMed1984

Body sodium level in hypertensive and normotensive rats: effects of dietary sodium levels and sodium loads.

Rats of the genetically hypertensive (GH) strain do not have an increased body sodium content or increased natriuresis of hypertension. Spontaneously hypertensive rats (SHR), on the other hand, have an increased body sodium content and an increased rate of excretion of a sodium load. They also have an increased appetite for salt. In a study on three groups of normotensive rats with high normal, low normal, and very low sodium intakes, respectively, body sodium content was highest with the highest intake and lowest with the lowest intake. At the age of 22 weeks, after being on these intakes for 6 weeks, all three groups were put on a low sodium intake. Body sodium content of the two groups with the previous higher intakes failed to fall to the level of the group with the previous lowest intake. Thus there may be a prolonged carryover effect of salt intake in rats. The results are discussed in terms of the set point theory for sodium homeostasis.

Animals↗
PubMed1983

24-h exchangeable sodium in genetically hypertensive and normotensive rats.

Total exchangeable sodium (Nae) was measured in NZ genetically hypertensive (GH) rats, random bred normotensives (N), Japanese spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats WKY. SHR rats were found to have significantly higher Nae than any of the other 3 strains. This confirms results previously obtained using a different method for Nae measurements.

Animals↗
PubMed1981

Blood pressure and hormonal changes following alteration in dietary sodium and potassium in young men with and without a familial predisposition to hypertension.

The blood pressures (BP) of the parents of a group of students were determined and two subgroups of students were defined, one with (PHT group) and one without (PNT group) a familial predisposition to hypertension. Observations were made in both groups during three periods of modified dietary electrolyte intake: (i) no-added sodium (low Na), (ii) no added sodium with potassium supplementation (low Na/high K), and (iii) sodium supplementation (high Na). The diets were given in random order. At the start of the trial, while the students continued their customary diet, the PHT group had higher systolic and diastolic pressures and plasma noradrenaline levels than the PNT group. At the end of 4 weeks of the high Na diet, the BP levels of both groups were significantly higher than those after the low Na diet. In contrast, when the low Na diet was supplemented for 2 weeks with potassium, BPs of the PHT group fell significantly, while those of the PNT group rose slightly. BP in the PHT group was significantly lower during the low Na/high K than during the high Na diet (systolic 10.5 mm Hg +/- 2.3 SE; diastolic 11.2 +/- 2.5, the changes being significantly different from those in the PNT group. The changes in plasma renin and aldosterone were similar in both groups during the different diets. Plasma noradrenaline fell in the PHT group, but rose in the PNT group when the low Na diet was supplemented with potassium. This fall in plasma noradrenaline in the PHT group during the low Na/high K diet correlated with the falls in systolic and diastolic BP. It is concluded that whereas young adults with a familial predisposition to hypertension behave similarly to those without such a predisposition in having a pressor response to a high sodium intake, they are peculiar in showing a depressor response to a high potassium intake.

Adult↗
PubMed1981

A comparison of the effects of propranolol and oxprenolol on forearm blood flow and skin temperature.

1 The effects of oxprenolol 80 mg and propranolol 80 mg on resting forearm blood flow (RFBF) and skin temperature were compared in seven normotensive subjects, for 4 h after an oral dose. 2 There was a significant fall of RFBF after propranolol (mean +/- s.e. mean 0.74 +/- 0.24 ml 100 g-1 min-1) compared to a smaller non-significant reduction after oxprenolol (0.35 +/- 0.19 ml 100 g-1 min-1). Propranolol produced a greater fall in heart rate than oxprenolol at all times except at 2.5 h. Three subjects experienced falls in skin temperature of over 4 degrees C with propranolol. There were no comparable falls after oxprenolol. 3 The results suggest that at the same dose oxprenolol has less effect on RFBF and skin temperature than propranolol.

Adult↗
PubMed1981

Acute effects of propranolol on the circulation and on oxygen uptake in conscious rats.

1 The acute effect of orally administered propranolol (100 mg/kg) on blood pressure, heart rate, cardiac output, venous pressure, haemoglobin concentration and oxygen uptake was studied in conscious rats. 2 Oxygen uptake was measured in a closed circuit respirometer and cardiac output determined by the direct Fick method. Other variables were measured by means of chronically implanted cannulae. 3 Significant falls occurred in heart rate (8.9%), cardiac output (30.5%), derived stroke volume (21.3%) and oxygen uptake (12.2%). 4 There were significant rises in arterial blood pressure (12.9%), derived arterial resistance (69%), arterio-venous oxygen difference (31.5%) and arterial haemoglobin concentration (6.3%). 5 A rise in venous pressure occurred in lightly anaesthetized rats but was only of borderline significance. 6 Correlations between the different variables revealed only one significant relationship, between heart rate and oxygen uptake. 7 It is concluded that only one primary site of action of propranolol has to be postulated to account for these findings, that of the well known negative inotropic and chronotropic effect on the heart.

Animals↗
PubMed1981

The action of propranolol on factors concerned with the delivery of oxygen to the tissues.

1 In a previous study in conscious rats, orally administered propranolol acutely lowered cardiac output by 30.5% and oxygen uptake by 12.2%, while oxygen extraction rose by 31.5%. The present study is concerned with the way in which the rat meets its oxygen requirements against such a fall in perfusion. 2 The effect of known concentrations of propranolol on haemoglobin-oxygen affinity was studied in vitro. The effect of orally administered propranolol (given acutely and chronically) was then determined and this was related to the concentration of the drug in plasma and red cells. Further studies were made on the action of propranolol on the Bohr effect and on arterial oxygen carriage. 3 In vitro, high concentrations of propranolol (1 x 10(-4) M) influenced haemoglobin-oxygen affinity in a biphasic manner and this was associated with changes in haematocrit and red cell and plasma pH. No change occurred in affinity after acute or chronic oral administration of the drug due to insufficient concentration in the blood. No direct action of the Bohr effect was detected. 4 Arterial oxygen content rose acutely due to an increase in haemoglobin concentration. 5 It is concluded that increased oxygen extraction in propranolol-treated rats is not explained by the actions of the drug on haemoglobin-oxygen affinity.

Animals↗
PubMed1981

Effect of captopril on blood pressure, total body sodium and fluid consumption of genetically hypertensive (GH) and normotensive (N) rats.

Captopril was administered in the drinking fluid to normotensive rats and rats of the New Zealand genetically hypertensive (GH) strain. It lowered BP in both strains of rat, particularly in rats deprived of sodium; in these rats BP rose again when the drug was stopped even though there was no access to sodium. Thus captopril appeared to lower blood pressure not by reduction in total exchangeable sodium but by some other mechanism, presumably inhibition of vasoconstriction. Total exchangeable sodium did not change significantly in rats treated with captopril and having access to salt in the drinking fluid, though it fell in rats deprived of sodium. Captopril caused an increase in fluid intake, particularly intake of 0.5% NaCl solution and this may have compensated for any loss of body sodium. It was not clear whether the thirst for water and the desire for salt were due to effects of captopril in the CNS or were secondary to increased excretion of salt and water.

Animals↗