bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in the Renin-Angiotensin-Aldosterone System and in Sodium and Potassium Balance during Development of Renal Hypertension in Rats
Authors: Leenen F. H. H. , Scheeren J. W. , Omylanowski D. , Elema J. D. , Van Der Wal B. , De Jong W.
Published: August 2015

1. The relationships between the renin-angiotensin-aldosterone system, sodium and potassium balance and systolic blood pressure were studied during development of moderate (160–180 mmHg; clip i.d. 0.25 mm) and severe (200–230 mmHg; clip i.d. 0.20 mm) renal hypertension in rats with an undisturbed contralateral kidney.

2. In severely hypertensive rats renin activity in the peripheral plasma increased from day 9, by which time the systolic blood pressure was elevated to 160–180 mmHg. The rate of total corticosteroid and aldosterone production in vitro increased from day 14 and plasma renin substrate concentration increased from day 24. In moderately hypertensive rats, none of these changes occurred.

3. During the first 10 days after the application of 0.25 and 0.20 mm clips, sodium and potassium retention/g gain in body weight were higher than in sham-operated controls. During the next 10 days, the positive balance stabilized in animals with a 0.25 mm clip whereas, in animals with a 0.20 mm clip, sodium and potassium balance returned to the level of the sham-operated controls through increased renal losses. Despite these changes the systolic pressure rose further in animals with a 0.20 mm clip.

4. The initial sodium retention could be a factor in the early rise of blood pressure and could account for the delay in the rise of peripheral plasma renin activity. The subsequent loss of the retained sodium and potassium during the development of severe hypertension could have facilitated the rise in peripheral plasma renin activity, but did not initiate this rise.
The Distribution of Ammonia between Extracellular and Intracellular Compartments of the Rat Brain
Authors: Hindfelt B.
Published: August 2015

1. The distribution of ammonia between extra- and intra-cellular compartments of the brain was evaluated in anaesthetized rats exposed to sustained hyperammonaemia and superimposed acute hypo- or hyper-capnia.

2. It is concluded that the concentration gradient for ammonia between arterial plasma and cerebrospinal fluid (CSF) cannot be explained by pH-dependent non-ionic diffusion of ammonia. A continuous uptake by the brain tissue of ammonia from the CSF is postulated and possible mechanisms are discussed.
Evidence for a Significant Contribution from Central Effects of Angiotensin in the Development of Acute Renal Hypertension in the Greyhound
Authors: Scroop G. C. , Katic F. P. , Brown M. J. , Cain M. D. , Zeegers P. J.
Published: August 2015

1. The importance of central vasomotor effects of endogenously generated angiotensin in the acute hypertensive response to renal artery constriction has been investigated in the anaesthetized greyhound.

2. When the central cardiovascular action of angiotensin was abolished by thermocoagulation of the areas postrema, the hypertensive response to renal artery constriction was reduced by half while the increase in plasma renin activity was unchanged.

3. It is concluded that central vasomotor effects of angiotensin play a significant role in renin-dependent hypertension.
The response of the Renin-Angiotensin System in Rats to the Injection of Angiotensin II Antibodies
Authors: Hackenthal E. , Bauknecht H. , Oster P.
Published: August 2015

1. Antibodies against angiotensin II were purified by affinity chromatography.

2. When injected intravenously into rats, the antibody distributed in the extracellular space with a half-time of 11 h and a distribution volume of about 10 ml/100 g body weight. The antibody was eliminated with a half-time of 7 days.

3. Plasma angiotensin II concentrations increased about 100-fold the control values 7 min after antibody injection and declined in parallel with the antibody concentration. It was calculated that only about 1–4% of the binding capacity of the antibody was occupied by angiotensin throughout the experiment.

4. Since the plasma renin concentration was normal, except during the short initial phase of stimulation, it is concluded that upon antibody injection the renin-angiotensin system rapidly, reached an equilibrium, with concentrations of free angiotensin close to or identical with normal concentrations.
Variation in the Proportions of Individual Pepsins Secreted by the Cat in Response to Vagal Stimulation and Hypoglycaemia
Authors: Wright Christine L. , Shaw B. , Sanders D. J. , Reed J. D.
Published: August 2015

1. Gastric juice was collected at regular intervals during electrical stimulation of the vagus in anaesthetized cats and during insulin hypoglycaemia in both anaesthetized and conscious cats. The total amounts of acid and pepsin secreted were similar in the three groups.

2. Pepsins were examined by agar-gel electrophoresis. Resting juice contained two pepsins, and up to nine pepsins could be detected after stimulation. Three patterns of pepsin secretion were found.

3. The most noticeable feature was the variation in the proportion of total pepsin attributable to the pepsin which migrated most rapidly during electrophoresis (pepsin 1). In response to insulin hypoglycaemia, anaesthetized cats secreted only a small proportion of total pepsin as pepsin 1 and conscious cats secreted a large proportion as pepsin 1. During direct electrical stimulation of the vagus, the proportion of pepsin 1 rose.

4. The possibility of a dependence of pepsin 1 secretion on vagal stimulation is discussed and the relevance of this to peptic ulcer and to vagotomy is considered.
Blockade of Renin Release by Lanthanum
Authors: Logan A. G. , Tenyi I. , Quesada T. , Peart W. S. , Breathnach A. S. , Martin B. G. H.
Published: August 2015

1. The effects of lanthanum on renin release and renal vasoconstriction were studied in the isolated perfused rat kidney.

2. Lanthanum reduced noradrenaline-induced renal vasoconstriction.

3. Lanthanum prevented isoprenaline-induced and glucagon-induced stimulation of renin secretion.
The Effect of Age on Deoxyribonucleic Acid Synthesis in Rat Adipose Tissue
Authors: Lewis B. M. , Hayes T. M.
Published: August 2015

1. Rats of four different age groups were injected intraperitoneally with labelled thymidine and killed 1, 7 or 12 days later.

2. The epididymal fat-pads were separated into fat-cells and stromal elements by collagenase digestion.

3. The incorporation of labelled thymidine into the deoxyribonucleic acid (DNA) of both fractions was greatest in the 6-week-old animals. Uptake was significantly decreased in 12- and 15-week-old animals and was lowest in 22-week-old rats.
Oestrogen Hypertension in Rats
Authors: Saruta T. , Nakamura R. , Saito I. , Kondo K. , Matuki S.
Published: August 2015

1. A large dose of oestrogen elevated the blood pressure in male Wistar rats.

2. Plasma renin substrate and renin activity increased significantly but plasma renin concentration was unchanged.

3. The increase in blood pressure induced by oestrogen was significantly reduced by salt loading, plasma renin concentration was suppressed and the increase in plasma renin activity was reduced.

4. The increase in plasma renin activity induced by the increase of plasma renin substrate concentration may play a role in oestrogen-induced elevation of blood pressure.
Effect of Parathyroid Extract on Renin Release in the Dog
Authors: McCredie D. A. , Powell H. R. , Rotenberg E.
Published: August 2015

1. A rapid increase in plasma renin activity occurred in dogs after intravenous administration of parathyroid extract.

2. This was not seen after injection of a purer parathormone preparation, or the solution used to dilute the parathyroid extract or calcitonin.

3. A vasoactive compound in parathyroid extract appears to provide the most likely explanation of this effect.
Treatment of Patients with Severe Hypertension by Inhibition of Angiotensin-Converting Enzyme
Authors: Johnson J. G. , Black W. D. , Vukovich R. A. , Hatch F. E. , Friedman B. I. , Blackwell C. F. , Shenouda A. N. , Share L. , Shade R. E. , Acchiardo S. R. , Muirhead E. E.
Published: August 2015

1. The results of the administration of the nonapeptide inhibitor (SQ 20,881) of the enzymatic conversion of angiotensin I into angiotensin II in twelve severe hypertensive patients are presented.

2. Administration of the compound was associated with a fall in blood pressure in ten of twelve patients.

3. Four patients had a normal plasma renin activity (PRA) with a range of 1.6–3.7 ng h−1 ml−1 and eight patients had a high PRA with a range of 5.0–74 ng h−1 ml−1. Two of the patients with normal PRA had no fall in blood pressure despite receiving 2 mg/kg of the compound. Two patients with normal PRA, however, did respond, thus indicating that a high PRA is not necessary for a response to the inhibitor compound.

4. It was found that haemodialysis or diuresis with frusemide enhanced the blood pressure response to the compound.

5. The presence of a measured low total blood volume was found to be associated with an exaggerated fall in blood pressure to a small dose of compound (0.125 mg/kg) in one patient.
The Use of Angiotensin-Converting Enzyme Inhibitor in the Diagnosis and Treatment of Hypertension
Authors: Gavras H. , Brunner H. R. , Laragh J. H. , Gavras I. , Vukovich R. A.
Published: August 2015

1. The anti-hypertensive effect of converting enzyme inhibition was evaluated in twenty-three hypertensive patients (seven renovascular, four essential, four malignant, one scleroderma, three chronic renal failure, four primary or idiopathic aldosteronism).

2. In sixteen patients a single injection (1–4 mg/kg) of the inhibitor produced an immediate anti-hypertensive effect, which lasted up to 16 h. In six patients the anti-hypertensive effect of the inhibitor was significantly improved after sodium depletion.

3. Plasma renin activities increased and plasma aldosterone concentrations decreased consistently except in idiopathic aldosteronism.

4. Converting enzyme inhibition provides a direct way of defining the degree of renin-dependency of the hypertension. Accordingly, it can be used diagnostically and for planning appropriate therapy. Therapeutically, it could be advantageous in hypertensive emergencies because of its safety, specificity and capacity to reduce aldosterone secretion.
Long-Term Propranolol Treatment of Resistant Arterial Hypertension in Haemodialysed Patients
Authors: Maggiore Q. , Biagini M. , Zoccali C. , Misefari M.
Published: August 2015

1. Propranolol was given to eight haemodialysed patients with resistant arterial hypertension for periods ranging from 6 to 16 months.

2. The treatment brought about an excellent control of blood pressure in all cases.

3. After withdrawal of propranolol plasma renin activity rose on average 40% compared with the value obtained during treatment. However, no significant relationship was found between the change in plasma renin activity and the change in the diastolic blood pressure.

4. Stopping propranolol resulted in a prompt rebound of arterial pressure toward pretreatment values. However, hypertension was always controlled on resuming drug treatment.

5. The results show that this form of hypertension can be controlled on a long-term basis with propranolol. However, the effect on blood pressure seems not to be mediated by suppression of renin secretion.
Effect of Oxprenolol on Catecholamines and Plasma Renin Activity: Acute Response to Frusemide in Hypertensive Patients
Authors: Muiesan G. , Alicandri C. , Rosei E. Agabiti , Motolese M. , Valori C.
Published: August 2015

1. Catecholamine plasma concentrations and urinary excretion were measured together with plasma renin activity in ten patients with essential hypertension and in five normal control subjects before and after a frusemide challenge.

2. The same procedure was repeated in the same subjects 3–4 days later after pretreatment with oxprenolol.

3. Noradrenaline plasma concentrations and urinary excretion increased significantly after frusemide in all cases, returning to normal values at 30 and 60 min. Adrenaline plasma concentrations and urinary excretion were unchanged.

4. Plasma renin activity increased significantly in seven patients with hypertension and normal renin basal values, remaining unchanged in three hypertensive patients with low-renin basal values.

5. Oxprenolol suppressed the response of noradrenaline and plasma renin activity to frusemide in all cases.
Beta-Adrenergic Receptors and Renin Release: Studies with Beta-Adrenoreceptor-Blocking Agents in the Conscious Rabbit
Authors: Weber M. A. , Oates Helen F. , Stokes G. S.
Published: August 2015

1. Plasma renin activity (PRA) and mean blood pressure were studied in conscious rabbits infused with beta-adrenoreceptor antagonists.

2. Oxprenolol and dl-propranolol each significantly reduced PRA and blood pressure, but prindolol, which had a strong blood pressure-lowering effect, increased PRA.

3. When prindolol was given to animals in which PRA and blood pressure had been reduced by dl-propranolol, PRA returned to control values but blood pressure remained low. Thus the increase in PRA caused by prindolol is not mediated by hypotension. These findings, together with the observation that compound H35/25 reduced PRA without altering blood pressure, suggest that the effects of the beta-adrenoreceptor-blocking drugs on blood pressure are unrelated to their effects on renin release.

4. Studies with d-propranolol and with blocking agents with either beta-1 or beta-2 specificity indicated that the effects of beta-adrenoreceptor blockade on renin are directly dependent upon their action on beta-adrenergic receptors, probably of the beta-2 type.
Effect of Propranolol on Blood Pressure in Normal and Hypertensive Rats
Authors: Conway J. , Darwin K. , Hilditch A. , Loveday B. , Reeves M.
Published: August 2015

1. Propranolol has been given orally in a dose sufficient to achieve beta-blockade throughout the day in normal rats, renal hypertensive animals with and without contralateral nephrectomy, spontaneously hypertensive and deoxycorticosterone (DOCA) hypertensive rats. The drug was given either after hypertension had become fully established or during the phase of rising blood pressure.

2. With this treatment, heart rate was reduced by approximately 100 beats/min in all experimental groups.

3. In established hypertension, treatment with propranolol for 7–9 days was ineffective in lowering blood pressure in any of the models of experimental hypertension. It also had no effect on blood pressure in normal animals.

4. Chronic treatment with propranolol during the phase of rising blood pressure had no effect in renal hypertensive animals. In spontaneous hypertension, the rise in blood pressure was limited to 28 mmHg with propranolol treatment as compared with 58 mmHg in control animals. Likewise, in DOCA hypertension, the rise in pressure was limited to 18 mmHg as compared with 46 mmHg in control animals.
Plasma Renin, Urinary Sodium Excretion and Vascular Disease
Authors: Doyle A. E. , Chua K. G. , Duffy S. , Louis W. J.
Published: August 2015

1. Urinary sodium excretion and plasma renin activity have been measured in a group of persons with untreated mild hypertension and in a control normotensive group.

2. Preliminary analyses of the data indicate that the daily sodium excretion was significantly higher in the hypertensive group but the plasma renin activity did not correlate significantly with the urinary excretion of sodium.

3. These findings suggest that sodium intake was significantly greater in a population with mild hypertension than in a comparable normotensive group.
Adrenergic Mechanisms in Human Hypertension and in Spontaneously Hypertensive Rats
Authors: Frohlich E. D. , Pfeffer M. A.
Published: August 2015

1. The role of adrenergic neuronal mechanisms in the development of early hypertension in man and the spontaneously hypertensive rat has been explored.

2. In both, a hyperkinetic circulatory state is associated with reduced parasympathetic and increased adrenergic cardiac influences.

3. Spontaneously hypertensive and normotensive control rats were treated with propranolol from conception until 12 weeks. Although heart rate and output remained reduced, there was no difference in growth or elaboration of pressure with respect to their untreated controls.

4. After another series of spontaneously hypertensive and control rats received cardiac autonomic blockade (atropine and timolol), they sequentially received alpha-adrenergic blockade (phenoxybenzamine), ganglionic blockade (trimethaphan) and smooth-muscle vasodilatation (hydralazine). These studies revealed only a small pressure differential between the two groups before hydralazine and still less thereafter; unlike the control rats, pressure in spontaneously hypertensive rats fell markedly after ganglionic blockade as a result of reduced output, indicating greater adrenergic control mediated through venoconstriction.

5. These findings indicate: increased cardiovascular adrenergic control in young spontaneously hypertensive rats, the hyperkinetic circulation merely reflecting one aspect of increased total cardiovascular input. Structural alterations seem to participate minimally.

6. These experimental observations closely resemble findings in early hypertensive man, and it is suggested that altered total cardiovascular adrenergic input is responsible for the elaboration, development, and maintenance of essential hypertension in man.
Central Serotonergic Neurons and Experimental Neurogenic and Renal Hypertension in the Rabbit
Authors: Chalmers J. P. , Wing L. M. H.
Published: August 2015

1. Rabbits received intracisternal injections of 5,6-dihydroxytryptamine (5,6-DHT) in order to ablate central serotonergic nerves and deplete central serotonin stores. Depletion was most marked in the spinal cord where serotonin concentration was reduced to less than 50% of that in rabbits given control injections.

2. In normal rabbits, intracisternal 5,6-DHT caused a transient reduction in arterial pressure, which was maximal 1 week after injection.

3. Intracisternal 5,6-DHT completely prevented the neurogenic hypertension produced by sinoaortic denervation in control animals and reversed it when given after sustained neurogenic hypertension had developed in denervated animals. These studies suggest that central serotonergic neurons participate in the baroreceptor reflex arc.

4. Intracisternal 5,6-DHT did not modify the renal hypertension that follows bilateral renal wrapping.
Renal Prostaglandin Synthesis in Experimental Renal-Clip Hypertension in the Rat
Authors: Pugsley D. , Beilin L. J. , Peto R.
Published: August 2015

1. The hypothesis that suppression of prostaglandin E synthesis by indomethacin exacerbates renal-clip hypertension in the rat was investigated in four groups of rats.

2. Indomethacin was shown to exacerbate hypertension in renal-clip animals.

3. Synthesis of prostaglandin E, determined by gas-liquid chromatography, was suppressed in medullary tissue from the hypertensive animals irrespective of indomethacin treatment.

4. The findings support the concept that prostaglandins participate in the blood pressure regulatory function of the kidney but pose a number of unsolved questions.
Relation of Intracellular K+ and Steroidogenesis in Isolated Adrenal Zona Glomerulosa and Fasciculata Cells
Authors: Mendelsohn F. A. , Mackie C.
Published: August 2015

1. Intracellular K+ content, water spaces and corticosterone output were measured in isolated zona glomerulosa and zona fasciculata-reticularis cell suspensions of rat adrenal cortex, after incubations in vitro under conditions designed to alter steroidogenesis.

2. Intracellular K+ of unpurified zona glomerulosa cells was not altered after stimulation of corticosterone output with serotonin. Similarly, with zona glomerulosa cells purified by unit gravity sedimentation, no change in intracellular K+ was detected after stimulation of steroidogenesis with serotonin or angiotensin II.

3. In high-potassium medium (final concentration 84 mmol/l), parallel increases in intracellular K+ and corticosterone output were observed with both unpurified and purified zona glomerulosa cells. However, a similar increase in intracellular K+ also occurred in high-potassium medium with zona fasciculata cells, whose steroid output is unresponsive to external potassium concentration ([K+]).

4. Ouabain at 10−5 mol/l depressed the intracellular [K+] of glomerulosa cells but did not alter basal or stimulated corticosterone output. Similar results were obtained with fasciculata cells.

5. Ouabain at 5×10−4 mol/l further depressed intracellular [K+] of glomerulosa cells and inhibited basal and stimulated corticosterone output. However, this concentration of ouabain also inhibited steroidogenesis in fasciculata cells.

6. These results demonstrate a variety of situations where changes in intracellular [K+] are dissociated from those in corticosterone output and indicate that intracellular [K+] cannot be the sole mechanism regulating steroidogenesis under these conditions.
Glucose Metabolites in Blood and Adipose Tissue of Obese Diabetic and Non-Diabetic Subjects
Authors: Page M. A. , Galton D. J.
Published: August 2015

1. Glucose 6-phosphate, fructose 6-phosphate, fructose diphosphate, glycerol phosphate and uridine diphosphate glucose have been measured in human adipose tissue and blood from obese subjects under fed and fasting conditions and in obese diabetic and non-diabetic subjects before and after an oral glucose load (100 g).

2. Adipose tissue metabolites expressed as nmol/g wet weight correlated inversely with adipocyte diameter.

3. After fasting, fructose diphosphate and glycerol phosphate in adipose tissue decreased significantly.

4. The basal concentrations of metabolites in blood and adipose tissue were maintained at similar concentrations in diabetic and non-diabetic subjects despite very different blood glucose concentrations.

5. The significant increase in adipose tissue glucose 6-phosphate after the glucose load seen in the non-diabetic but not in the diabetic subjects suggests that glucose uptake is decreased in the diabetic adipocyte.
Effect of Cellulose Phosphate on Calcium and Magnesium Homeostasis: Studies in Normal Subjects and Patients with Latent Hypoparathyroidism
Authors: Parfitt A. M.
Published: August 2015

1. The bivalent cation-binding agent, cellulose phosphate, was given for 6 days to four normal subjects and six patients with latent hypoparathyroidism (diagnosed by impaired response to EDTA infusion), all of whom were on a moderately low calcium diet.

2. In normal subjects, there was a prompt and sustained fall in urinary calcium with no change in plasma calcium, indicating increased tubular reabsorption. Plasma and urinary magnesium fell, without increase in tubular reabsorption. The urinary total hydroxyproline increased and Tm,P/ glomerular filtration rate fell after 2 days; these changes were transient and were consistent with a transient increase in parathyroid hormone secretion.

3. In the hypoparathyroid patients, urinary calcium fell more slowly and a fall in plasma calcium occurred in several subjects, the extent and duration of which corresponded with parathyroid status determined by EDTA infusion. Urinary conservation of calcium was impaired but plasma and urinary magnesium fell as in normal subjects. Urinary total hydroxyproline did not change and Tm,P/glomerular filtration rate fell more slowly than in the normal subjects.

4. The relative contributions of increased tubular reabsorption and reduced filtered load to calcium conservation in response to calcium depletion depend on the prevailing level of parathyroid function; the former is more important when parathyroid function is normal, the latter when parathyroid function is impaired.

5. In the detection of reduced parathyroid reserve, the assessment based on the plasma calcium response to cellulose phosphate agrees closely with the assessment based on the degree of recovery from EDTA-induced hypocalcaemia.
Effect of Cellulose Phosphate and Dietary Calcium Restriction in Primary Hyperparathyroidism
Authors: Parfitt A. M.
Published: August 2015

1. The bivalent cation-binding agent, cellulose phosphate, together with a low calcium diet was given for 6 days to nine patients with primary hyperparathyroidism subsequently verified at surgery.

2. Urinary calcium fell promptly by 8·4 mmol/24 h, and by 70%, and reached amounts below 4·0 mmol/24 h in five of the nine patients. The magnitude of fall may have been related to increased synthesis of vitamin D by the skin in a sub-tropical environment. Plasma magnesium fell steadily and urinary magnesium fell by 80%.

3. The plasma calcium showed two types of response. In five patients there was no significant change because a reduction in calcium load was offset by a further increase in the already high tubular reabsorption of calcium. In the remaining four patients, the tubular reabsorption of calcium was at a higher level initially and failed to increase further on the experimental regime, with a corresponding fall in plasma calcium.

4. The hypercalcaemia of primary hyperparathyroidism can be explained by increased gastrointestinal absorption and increased renal tubular reabsorption of calcium; net bone resorption makes only a small contribution but an additional factor dependent on the blood-bone equilibrium is not ruled out.

5. Comparison with other published data suggests that the fall in urinary calcium in response to a calcium-depleting regimen is prevented by concurrent depletion of inorganic phosphate and may be enhanced by concurrent depletion of magnesium.

6. Persistence of hypercalcaemia combined with an increase in tubular reabsorption of calcium in response to cellulose phosphate may be of diagnostic value in suspected primary hyperparathyroidism.

7. Cellulose phosphate may be of value in stone prevention in patients with primary hyperparathyroidism who are unsuitable for surgical treatment.
Determination of Platelet and Fibrinogen Half-Life with [75Se]Selenomethionine: Studies in Normal and in Diabetic Subjects
Authors: Ferguson J. C. , Mackay N. , Philip J. A. D. , Sumner D. J.
Published: August 2015

1. Simultaneous platelet and fibrinogen survival studies were carried out on a group of seven normal persons and eleven diabetic patients.

2. Survival time was calculated: (a) by measuring the interval between 50% of the maximum radioactivity in the anabolic phase and 50% of the maximum radioactivity in the catabolic phase, and (b) by fitting an exponential function to the decay phase of the curve.

3. With the first method, the normal group had a mean platelet survival which did not differ significantly from that in the diabetic group. With the second method, however, the platelet half-life in the diabetic patients was significantly shorter than in the normal subjects.

4. Fibrinogen survival was significantly shorter in the diabetic group with either method.

5. It is concluded that there is an increased utilization of platelets and fibrinogen in diabetic subjects.
Adrenal Weight and Catecholamine Content in Renal and Calciferol-Induced Hypertension in Rabbits
Authors: Angell-James Jennifer E. , Powis D. A.
Published: August 2015

1. Hypertension was produced in rabbits by unilateral renal encapsulation combined with contralateral nephrectomy or by the administration of calciferol and calcium lactate.

2. Weighed post mortem, the adrenal glands from the two hypertensive groups were significantly heavier than those from normotensive animals of similar weight. There was a direct correlation between the adrenal gland weight and the mean arterial blood pressure measured at the time of the terminal experiment.

3. The catecholamine content of the adrenal glands from the two groups of hypertensive animals was similar to that of the normotensive animals.

4. There was histological evidence of adrenal cortical hypertrophy in the glands of the hypertensive groups of animals.
Cardiac Effects of Lead in Drinking Water of Rats
Authors: Moore M. R. , Meredith P. A. , Goldberg A. , Carr K. E. , Toner P. G. , Lawrie T. D. V.
Published: August 2015

1. There is no known cause for the increased mortality due to ischaemic heart disease in soft water areas. Since the lead concentration of soft water is elevated in houses with lead plumbing, studies have been carried out to determine the effects of lead on the heart of rats.

2. Rats were given drinking water containing lead for 1 year at concentrations similar to those found previously in Glasgow, which has a soft water supply.

3. There was increasing deposition of lead in the heart and a fall in the cardiac levels of the enzymes ferrochelatase and δ-aminolaevulinic acid dehydratase. These changes are maximal after 6 months, when there were marked electron-microscopic changes in the myocardium and myocardial mitochondria.

4. Further studies are needed to determine whether lead is a cause of the increased mortality from ischaemic heart disease in soft water areas.
Effect of Phenylalanine and Its Metabolites on the Metabolism of Leucocytes and Lymphocytes
Authors: Bradley D. M. , Mahler R. F.
Published: August 2015

1. The pathogenesis of the mental retardation in phenylketonuria remains obscure. Leucocytes have proved of value in the study of other inborn errors of metabolism. The lymphocyte is a suitable model cell for the study of mammalian metabolism, because of its ability to divide in vitro in response to various stimuli.

2. We have examined the effects of phenylalanine, phenylpyruvate, phenyl-lactate and phenylacetate on the human leucocyte and the resting and phyto-haemagglutinin-stimulated rabbit lymphocyte.

3. Phenylpyruvate and phenyl-lactate reduced acetate incorporation into leucocyte lipid by 38% and 48% respectively. Only phenyl-lactate reduced acetate incorporation into the resting and stimulated lymphocyte, by 20% and 34% respectively.

4. Glucose incorporation into leucocyte lipid was unaffected by phenylalanine, phenylpyruvate and phenyl-lactate. Only phenyl-lactate inhibited (46%) the production of CO2 from glucose.

5. Phenylalanine and leucine incorporation into trichloroacetic acid-insoluble material of resting and stimulated lymphocytes was inhibited by phenyl-lactate (10–42%), phenylpyruvate (27–57%) and phenylacetate (19–39%).

6. Uridine incorporation into resting and stimulated cells was inhibited by phenyl-lactate (22–26%), phenylpyruvate (42–52%) and phenylacetate (20%).

7. Thymidine incorporation into resting lymphocytes was reduced by phenyl-lactate, phenylpyruvate, phenylacetate and phenylalanine by 12–26%. Incorporation into the stimulated cell was inhibited by phenylpyruvate and phenyl-lactate (90%) and phenylacetate (66%).

8. Phenylalanine inhibited lymphocyte pyruvate kinase and phenylpyruvate inhibited citrate synthetase.

9. These results are compared with published data relating to experimental hyperphenylalaninaemia and the effects of these metabolites on nervous tissue in vitro.
The Effects of a Diphosphonate and Dietary Calcium on the Metabolism of Vitamin D3 (Cholecalciferol) in the Chick
Authors: Taylor Carol M. , Mawer E. Barbara , Reeve A.
Published: August 2015

1. Vitamin D-deficient chicks, maintained on a diet adequate in calcium and treated with ethane-1-hydroxy-1,1-diphosphonate for 2 days before a single oral dose of cholecalciferol (vitamin D3), converted the vitamin into 24,25-dihydroxycholecalciferol instead of into the normal metabolite 1,25-dihydroxycholecalciferol.

2. This inhibition of the renal 1-hydroxylase disappeared on withdrawal of the diphosphonate.

3. Kidneys from chicks given diphosphonate for 12 days converted 25-hydroxycholecalciferol into 24,25-dihydroxycholecalciferol on incubation in vitro.

4. The inhibition of the 1-hydroxylase was markedly accelerated by treating the birds with cholecalciferol.

5. No inhibition of renal 1-hydroxylation was observed in birds maintained on a diet low in calcium.

6. A possible mechanism producing this effect is discussed.
A Study of Relations between the Absorption of Amino Acids, Dipeptides, Water and Electrolytes in the Normal Human Jejunum
Authors: Silk D. B. A. , Fairclough P. D. , Park Nicola J. , Lane Annette E. , Webb Joan P. W. , Clark M. L. , Dawson A. M.
Published: August 2015

1. A double-lumen perfusion technique was used to study the effect of a wide range of concentrations of the dipeptide glycyl-l-alanine and its constituent amino acids on water and electrolyte absorption from iso-osmotic solutions in the upper jejunum of normal human subjects.

2. There was no significant absorption of water and electrolytes from sodium chloride solution (150 mmol/l) but the presence of the dipeptide or its constituent amino acids stimulated water and electrolyte absorption.

3. Water absorption reached a peak at increasing amino acid and dipeptide concentrations and then tailed off. Our data suggest that the tailing off is not solely due to the diminished sodium content of the solutions.

4. During perfusion of the dipeptide-sodium chloride and amino acid-sodium chloride solutions solute and water were absorbed as an iso-osmotic solution. Analysis of the results indicates that this could occur at high dipeptide concentrations only if the majority of the dipeptide enters the cell intact.
Effects of Pent-4-Enoic Acid on Renal Free Water, Bicarbonate and Phosphate Excretion in the Dog
Authors: Kleinman J. G. , Levin M. L.
Published: August 2015

1. The effects of pent-4-enoic acid, an inhibitor of fatty acid oxidation, were studied in dogs undergoing water diuresis and acetazolamide diuresis. Free water excretion and distal solute delivery were increased when infusion of pent-4-enoic acid was superimposed on an increasing mannitol diuresis.

2. Bicarbonate excretion increased significantly when infusion of pent-4-enoic acid was superimposed on maximum acetazolamide diuresis.

3. Phosphate excretion exceeded 90% of filtered load when pent-4-enoic acid was administered under stable free water conditions and increased significantly when pent-4-enoic acid was superimposed on stable acetazolamide diuresis.

4. The results are interpreted as indicating inhibition of proximal tubular reabsorption by pent-4-enoic acid, emphasizing the importance of fatty acids as a major fuel for proximal tubular metabolism.
Respiratory Responses to Simultaneous Static and Rhythmic Exercises in Humans
Authors: Wiley R. L. , Lind A. R.
Published: August 2015

1. Six male subjects performed simultaneous static (hand-grip) and rhythmic (bicycle ergometer) exercises while their respiratory responses were measured.

2. Oxygen consumption increased with the intensity of rhythmic work load, with a modest additional oxygen consumption accompanying the addition of static effort during the rhythmic exercise.

3. Minute ventilation (V̇E) increased directly with rhythmic exercise, but increased disproportionately to the metabolic need when static effort was added. The mean increment of V̇E elicited by the static exercise influence was nearly constant at 20 1/min, regardless of the rhythmic load present.

4. Possible reflex mechanisms which result in disruption of the normally well-matched ventilation and metabolic oxygen demands whenever static effort is present are discussed.
Effects of Metiamide on the Human Stomach
Authors: Thjodleifsson B. , Wormsley K. G.
Published: August 2015

1. The effect of metiamide on gastric acidity in man has been studied. Solutions of hydrochloric acid or glucose were instilled into the stomach and the subsequent rates of gastric secretion and emptying, and the disappearance of acid within the stomach, were measured.

2. Metiamide inhibited the gastric secretory response to the instilled acid and glucose solutions but did not change the overall pattern of emptying of the instilled solutions.

3. During administration of metiamide, there was a net loss of acid from within the gastric lumen. The rate of disappearance of acid from the instilled acid solution was small and not sufficient in magnitude to account for the metiamide-evoked decrease in the concentration of acid secreted in response to pentagastrin.

4. We conclude that metiamide does not inhibit gastric secretion by altering the ‘barrier’ function of the gastric mucosa.
Disturbances in Glucose Metabolism in Patients with Liver Damage Due to Paracetamol Overdose
Authors: Record C. O. , Chase R. A. , Alberti K. G. M. M. , Williams R.
Published: August 2015

1. Intravenous glucose tolerance tests were performed in fourteen patients with mild or moderate liver damage due to paracetamol overdose.

2. In patients managed conservatively there was glucose intolerance associated with a diminished early insulin response to glucose, suggesting inadequate nutrition in the period between the overdose and the glucose tolerance test.

3. Patients given intravenous glucose supplements to maintain nutrition were also glucose intolerant and, in these, insulin responses to glucose were normal. The decreased fractional disappearance rate was partly due to an increase in glucose distribution space and partly due to a decrease in absolute glucose disappearance rate.

4. Impaired gluconeogenesis was suggested by mild fasting hypoglycaemia in four patients and raised fasting blood lactate concentrations. Serum growth hormone concentrations showed a paradoxical increase after glucose.

5. All these variables had returned to normal in four patients re-tested after recovery.
Arterial Catecholamines in Hypoxic Exercise in Man
Authors: Clancy L. J. , Critchley J. A. J. H. , Leitch A. G. , Kirby B. J. , Ungar A. , Flenley D. C.
Published: August 2015

1. We measured the minute ventilation and arterial blood catecholamine concentrations in four normal men standing and at two levels of moderate treadmill exercise breathing 14% oxygen or air.

2. Minute ventilation was significantly higher during hypoxic exercise than during normoxic exercise at an oxygen uptake of 1500 ml/min.

3. Arterial plasma noradrenaline during hypoxic exercise at an oxygen uptake of 1500 ml/min was significantly greater than at rest.

4. Arterial plasma noradrenaline during normoxic exercise at an oxygen uptake of 1500 ml/min was not elevated above the resting concentration.

5. The results are compatible with the suggestion that increased concentrations of arterial plasma noradrenaline contribute to the hypoxic potentiation of the respiratory response to moderate exercise.
Potassium Depletion Induced by Vasopressin and Overhydration in the Rabbit
Authors: Barraclough M. A.
Published: August 2015

1. In order to study the effect of overhydration on body potassium, experiments were performed on pair-fed rabbits, one of which was maintained continuously on vasopressin and given extra water (60–90 ml day−1 kg−1) for 6–8 days, while the other served as control.

2. Overhydrated rabbits excreted significantly more potassium (53%) in their urine than control rabbits and accumulated a mean potassium deficit of 65·0 mmol, significantly higher than the mean value of 37·1 mmol in the control rabbits.

3. In the overhydrated rabbits, potassium fell significantly in both erythrocytes, from 266 to 173 mmol/kg of dry cells, and also in muscle, from 435 to 341 mmol/kg of fat-free dry solids. Neither changed significantly in the control animals.

4. Overhydration in the presence of vasopressin leads to potassium depletion in the rabbit and a similar phenomenon might be expected in man. Potassium depletion due to overhydration might account for the hypokalaemia and reduction in exchangeable potassium observed in some patients with the syndrome of inappropriate secretion of antidiuretic hormone.
Urinary Concentration and Dilution after Unilateral Nephrectomy in the Rat
Authors: Emmanouel D. S. , Lindheimer M. D. , Katz A. I.
Published: August 2015

1. The effects of unilateral nephrectomy on urinary concentration and dilution were studied in Sprague—Dawley rats. To exclude incomplete suppression of antidiuretic hormone, free water formation was also studied in rats with congenital diabetes insipidus (Brattleboro strain).

2. Urinary solute-free water formation was similar in Sprague—Dawley and Brattleboro rats. Unineph-rectomized animals excreted a water load promptly and diluted their urine to the same degree as control rats. Maximal values for Cwater and TCwater per kidney were higher after nephrectomy, but were similar to those of control rats at comparable rates of fluid delivery to the distal nephron. Renal tissue osmolality was similar in uninephrectomized and sham-operated animals, indicating that non-antidiuretic hormone-dependent backflux of filtrate was the same in the two groups. The only defect observed in uninephrectomized animals was a small reduction in maximal urine osmolality.

3. These results demonstrate that free water formation and reabsorption are unaffected by unilateral nephrectomy and suggest that, in the remaining kidney, filtrate reabsorption along the entire nephron increases in proportion to the increment in glomerular filtration.
The Nylon Column Dye Test: A Possible Screening Test of Phagocyte Function
Authors: Segal A. W. , Peters T. J.
Published: August 2015

1. A simple quantitative test has been developed to investigate phagocyte function.

2. This test is performed by the addition of Nitroblue Tetrazolium to whole blood, followed by the isolation of leucocytes on a column of nylon wool. Dye reduction by phagocytes is apparent as a blue coloration of the column due to the formation of formazan. The formazan can be extracted from the column and measured spectrophotometrically.

3. The formation of formazan was found to be directly related to the number of phagocytes in blood.

4. Two patients with chronic granulomatous disease gave abnormal results, suggesting that the test procedure may be of value as a screening procedure for this disease.
Plasma Squalene as an Index of Cholesterol Synthesis
Authors: Nestel P. J. , Kudchodkar B.
Published: August 2015

1. Seven subjects were studied before and after the rate of cholesterol synthesis was altered with drugs or dietary cholesterol.

2. The rate at which plasma free cholesterol was formed from squalene during constant infusions of radioactive mevalonate increased with colestipol treatment, decreased with clofibrate treatment and decreased when cholesterol was added to the diet. The plasma squalene concentration showed corresponding changes, confirming that its measurement may qualitatively define changes in cholesterol synthesis.

3. The mean plasma squalene concentration in seven hypertriglyceridaemic, slightly overweight subjects was significantly higher than in six hypercholesterolaemic subjects, which is consistent with other evidence for increased cholesterol synthesis in hypertriglyceridaemia.
The Fate of Circulating Lactate Dehydrogenase-5 in the Rabbit
Authors: Qureshi A. R. , Wilkinson J. H.
Published: August 2015

1. In an attempt to determine the mechanism whereby enzymes are removed from the circulating plasma, purified rabbit-muscle lactate dehydrogenase-5 was labelled with 125I and injected intravenously into rabbits. During the first hour after injection enzyme activity and radioactivity disappeared from the plasma at comparable fast rates, which are attributed mainly to distribution of the enzyme throughout the extracellular fluid. This was followed by a phase lasting about 7 h during which enzyme activity disappeared at a faster rate than the radioactivity, an observation indicating either intravascular breakdown of the enzyme protein or its degradation in the tissues, followed by release of labelled fragments into the circulation. Enzyme activity then reached a constant value and the plasma radioactivity continued to decrease at a slower exponential rate; it is suggested that this is due to removal of breakdown products.

2. The radioactivity of the tissues was measured at various time-intervals after injection. After 2 h and 8 h highest concentrations were found in the spleen, liver, jejunum and duodenum. Relatively high concentrations were also found in the intestinal juices throughout the period of study, an observation which suggests that discharge via the small intestine is a major route whereby inactivated enzyme fragments are removed from the circulation.

3. About 5% of the injected radioactivity was recovered in the faeces during the first 3 days, and the urine accounted for 73% during the same period. About 35% of the urinary radioactivity was shown by silver nitrate precipitation and by chromatography to consist of free iodide and the remainder appeared to consist of radio-iodinated amino acids or peptides. Free mono- and di-iodotyrosine were identified among the products. These results suggest that further breakdown in the intestine is followed by absorption of the products, which are excreted in the urine.
Effect of Liver Failure on the Ventilatory Response to Hypoxia in Man and the Goat
Authors: Stanley N. N. , Kelsen S. G. , Cherniack N. S.
Published: August 2015

1. The ventilatory responses to transient and steady-state hypoxia were measured in ten patients with hepatic cirrhosis and in ten healthy control subjects. Successive measurements of these responses were also obtained in six goats before and after the experimental production of liver failure. Changes in the effect of steady-state hypoxia on the ventilatory response to hypercapnia were evaluated by successive studies in another goat.

2. In spite of a respiratory alkalosis during liver failure, the response to transient hypoxia was greater in the patients than in the control subjects. This response was increased after the onset of liver failure in all the goats.

3. In healthy humans and goats the responses to transient and steady-state hypoxia were similar in magnitude. During liver failure there was a disparity between the size of these responses, since the ventilatory increment evoked by steady-state hypoxia was unchanged in spite of the increase in response to transient hypoxia. Steady-state hypoxia consistently enhanced the ventilatory response to hypercapnia in a healthy goat, but frequently depressed the response to hypercapnia during liver failure.

4. The findings suggest that liver failure heightens the sensitivity of the peripheral chemoreceptors to the hypoxic stimulus, but may increase the tendency of the medullary centres to become depressed in hypoxia.
Measurement by Venous Occlusion Plethysmography of Blood Flow through Surgically Created Arteriovenous Fistulae in the Human Forearm
Authors: Wallace W. F. M. , Jamison J. P.
Published: August 2015

1. Plethysmographs containing the hand plus forearm were used to measure blood flow in patients with a surgically created arteriovenous fistula in one forearm.

2. Apparent flow rate was stable over a limited range of collecting pressures; the absolute value of these pressures varied from patient to patient.

3. After arterial occlusion, blood flow increased by a similar amount on the normal side and on the side with the fistula.

4. Occlusion of fistular flow produced no significant change in heart rate.

5. Fistular flow, estimated as the difference between flow on the two sides, averaged 525 ml/min in seventeen patients.
Plasma Renin Activity as a Function of Age in Two New Strains of Spontaneously Hypertensive and Normotensive Rats
Authors: Vincent Madeleine , Dupont Jeanne , Sassard J.
Published: August 2015

1. Strains of spontaneously hypertensive and normotensive rats were selected by repeated inbreeding.

2. Brief ether anaesthesia was shown to produce a two- to three-fold increase in plasma renin activity in both strains.

3. Plasma renin activity was significantly higher in young spontaneously hypertensive than in normotensive rats of the same age (5–7 weeks). After the ninth week plasma renin activity decreased and, at week 45, became significantly lower in hypertensive than in normotensive rats.

4. When hypertension was established a significant inverse relationship was found between plasma renin activity and systolic blood pressure in spontaneously hypertensive and in normotensive rats.

5. It seems unlikely that the renin—angiotensin system plays a major role in the maintenance of the established spontaneous hypertension in this strain. However, renin hypersecretion may be important in the early pre-hypertensive stage of genetic hypertension in rats.