bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypertension Induced by Prolonged Intracoronary Administration of Dobutamine in Conscious Dogs
Authors: Liard J.-F.
Published: August 2015

1. In order to determine if a sustained increase in cardiac output can lead to hypertension, seven conscious dogs were given a continuous infusion of dobutamine, a powerful stimulant of cardiac inotropism, into the left coronary artery for a 7 day period while arterial pressure, cardiac output (electromagnetic flowmeter) and heart rate were measured.

2. The infusion technique (1·5 × 10−8 mol min−1 kg−1, intracoronary) was selected after short-term experiments showed that it increased cardiac output more effectively than intravenous infusion at the same rate.

3. The rise in cardiac output elicited by intracoronary infusion of dobutamine was largest during the first 6 h of the 7 days administration, at which time calculated peripheral resistance was decreased. Subsequently, cardiac output returned progressively toward its control value whereas mean arterial pressure remained elevated (by an average of 20–25 mmHg) and peripheral resistance increased significantly.

4. Measurements of blood and extracellular fluid volumes as well as plasma renin activity indicated that these factors were not involved in the blood pressure increase.

5. When the infusion was ended, arterial pressure fell rapidly but peripheral resistance remained elevated during the first 6 h. Cardiac output fell after 2 and 6 h to a value below that of the pre-infusion control. After 1 day and subsequently, blood pressure became normal, as did the peripheral resistance and cardiac output.

6. Both at the onset and offset transients of this model of hypertension, changes in cardiac output preceded changes in peripheral resistance. These experiments may give experimental support to the concept of cardiogenic hypertension.
An Interpretation of the Intravenous Glucose Tolerance Test in the Light of Recent Findings on the Kinetics of Glucose and Insulin in Man
Authors: Cunningham V. J. , Heath D. F.
Published: August 2015

1. A theoretical investigation of the intravenous glucose tolerance test has been carried out based on recent findings on the kinetics in man of insulin production, distribution, disposal and action, and of glucose turnover and distribution.

2. A good fit to published data on four groups of subjects required a scheme that includes two extravascular glucose spaces and separate venous, arterial and capillary volumes. The fit to the data was little affected by variations within the physiological range of venous and arterial volumes, cardiac output, glycosuria and the properties of the less-accessible glucose pool.

3. The only variables needed to account for the differences between the groups were kinsulin (a measure of the mean sensitivity of insulin-dependent tissues to insulin action) and the readily accessible glucose space.

4. Three published schemes for insulin kinetics were used. They were all consistent with the data and gave very similar relative values of kinsulin in the four groups.

5. It is shown that a rigorous interpretation of the test requires a knowledge of the hepatic response to the glucose load during the test. These effects are not well characterized in pathological states, e.g. diabetes and injury. Consequently conclusions about insulin resistance in these states drawn only from the test are doubtful.
Relationships between Cardiac Output, Heart Rate and Blood Volume in Essential Hypertension
Authors: Chau N. P. , Safar M. E. , Weiss Y. A. , London G. M. , Simon A. Ch. , Milliez P. L.
Published: August 2015

1. Cardiac haemodynamics were determined in 196 male untreated subjects, comprising 98 normotensive individuals and 98 hypertensive patients of the same age.

2. In order to study the haemodynamic change in hypertension, a new methodology was proposed. The whole population was classified by increasing diastolic pressures and divided into overlapping subgroups. From subgroup to subgroup, mean values of different haemodynamic variables were plotted against mean values of diastolic pressures. Three phases could be observed in the changes of these variables. In the first phase (for mean diastolic pressures under about 80 mmHg), the rise in pressure was associated with a decrease in blood volume and with an increase both in cardiac output and heart rate. In the second phase (for mean diastolic pressures between 80 mmHg and 95 mmHg approximately), heart rate, cardiac output and blood volume remained at the same values. In the third phase (for mean diastolic pressure above approximately 95 mmHg), heart rate remained elevated while the rise in pressure was associated with a decrease both in cardiac output and blood volume.

2. In the same subgroups, the correlations between cardiac output and heart rate and between cardiac output and blood volume were studied. The correlation between cardiac output and heart rate was significant only in normotensive ranges while the correlation between cardiac output and blood volume was significant only in hypertensive ranges.

3. Classical statistical tests, performed in distinct subgroups, confirmed the above observations on the changes of mean values and correlations.

5. The study provided evidence that cardiac output was predominantly controlled by neural mechanisms within the normotensive range and by volume mechanisms within the hypertensive range.
The Degradation of Human Glomerular Basement Membrane with Purified Lysosomal Proteinases: Evidence for the Pathogenic Role of the Polymorphonuclear Leucocyte in Glomerulonephritis
Authors: Davies M. , Barrett A. J. , Travis J. , Sanders E. , Coles G. A.
Published: August 2015

1. Human polymorphonuclear leucocyte elastase and cathepsin G were incubated with preparations of isolated human glomerular basement membrane at neutral pH and 37°C.

2. The ability of these enzymes to degrade glomerular basement membrane was followed by the release of hydroxyproline. Both proteinases released considerable amounts of hydroxyproline.

3. By using Sephadex G-100 it was shown that the solubilized basement membrane fragments appeared as a single peak and had a molecular weight of over 100 000. These proteins after reduction were analysed by sodium dodecyl sulphate-gel electrophoresis to examine their subunit pattern and determine their molecular size.

4. The released basement membrane proteins gave at least four precipitin lines with a rabbit anti-(glomerular basement membrane) antiserum.

5. These results support the concept that polymorphonuclear leucocyte neutral proteinases play an important role in the pathogenesis of glomerulonephritis.

6. At acid pH values cathepsin B also released hydroxyproline from human glomerular basement membrane but the lysosomal carboxyl proteinase, cathepsin D, had no action.
Family Studies on the Activity of Uroporphyrinogen I Synthase in Diagnosis of Acute Intermittent Porphyria
Authors: Astrup E. G.
Published: August 2015

1. Ten subjects with acute intermittent porphyria from three different families, and 92 relatives, were investigated for their erythrocyte uroporphyrinogen I synthase (EC 4.3.1.8) activities by the spectrofluorimetric method described and for their urinary concentrations of δ-aminolaevulinic acid and porphobilinogen.

2. The mean uroporphyrinogen I synthase activity in 41 healthy women and 41 healthy men showed a significant (P < 0·001) sex difference.

3. A reduction of about 32% of the enzyme activity was observed in the porphyric subjects as compared with values in healthy normal subjects and the values from the porphyric subjects overlapped those of the reference subjects.

4. With the values from the normal subjects in each family used as reference, however, the enzyme activity in normal subjects was twice that in affected subjects. Thus by using an internal family reference uroporphyrinogen I synthase values became more reliable in disclosing latent cases of the disorder. Furthermore, these measurements were shown to have a stronger discriminative power than urinary δ-aminolaevulinic acid and porphobilinogen determinations.
Control of Breathing in Patients with Chronic Obstructive Lung Disease
Authors: Šorli J. , Grassino A. , Lorange G. , Milic-Emili J.
Published: August 2015

1. Using the mouth occlusion pressure technique, we have studied the control of breathing in seven hypercapnic and eight non-hypercapnic patients with chronic obstructive lung disease.

2. When breathing room air, pulmonary ventilation, mean inspiratory flow and P0·1 (mouth occlusion pressure developed 0·1 s after the onset of occluded inspiration at functional residual capacity) were not significantly different between the two groups of patients. Tidal volume, however, was significantly lower in the hypercapnic than in the non-hypercapnic patients, as a result of a significantly lower duration of inspiration.

3. The lower tidal volume in the hypercapnic patients leads to decreased alveolar ventilation, and appears to be the main cause of retention of carbon dioxide.
A Radioimmunoassay for 1,25-Dihydroxycholecalciferol
Authors: Clemens T. L. , Hendy G. N. , Graham R. F. , Baggiolini E. G. , Uskokovic M. R. , O'Riordan J. L. H.
Published: August 2015

1. 1α,25-Dihydroxy-25-hemisuccinate cholecalciferol has been synthesized and conjugated to bovine serum albumin.

2. This conjugate is immunogenic; when injected into rabbits antibodies of high affinity for 1α,25-dihydroxycholecalciferol were obtained.

3. Vitamin D metabolites lacking the 1α-hydroxy group were of lower cross-reactivity with the antibodies.

4. By using these antibodies and 1α,25-[23,24-3H]dihydroxycholecalciferol as tracer a sensitive radioimmunoassay has been developed capable of detecting 20 pg of 1α,25-dihydroxycholecalciferol.
The Effect of Acute Extracellular Volume Expansion on Sodium Chloride Reabsorption in the Diluting Segment in Man
Authors: Ish-Shalom N. , Rapoport J. , Chaimovitz C. , Better O. S.
Published: August 2015

1. The effect of extracellular volume expansion (ECVE) during water diuresis, and of water diuresis alone, on the formation of free water in man was compared.

2. ECVE reduced free water formation at any given rate of distal delivery compared with water diuresis. Thus, ECVE depresses distal sodium chloride reabsorption.

3. This attenuation of free water formation occurred both when urine flow (V/100 ml glomerular filtration rate) and distal chloride delivery [(Cwater + CCl)/100 ml glomerular filtration rate] were used as the terms for distal delivery.

4. We suggest that the distal depression of sodium chloride reabsorption after ECVE is probably due to a direct inhibition of distal sodium chloride transport mechanisms, and not to the flooding of the diluting site by the poorly reabsorbable bicarbonate ion.
Structure—Activity Relations of the Fibrinolytic Response to Vasopressins in Man
Authors: Cash J. D. , Gader A. M. A. , Mulder J. L. , Cort J. H.
Published: August 2015

1. The systemic plasminogen activator response has been examined after intravenous infusion of the following peptides related to neurohypophyseal hormones in approximately equimolar dosages into informed, consenting human volunteer subjects: (a) the natural nonapeptides: lysine- and arginine-vasopressin, oxytocin and arginine-vasotocin, (b) the N- and C-terminal tripeptide fragments of vasopressin and (c) four vasopressin analogues without pressor activity, altered at the N-terminus, the disulphide bridge and/or sequence position 8 in the C-terminal tripeptide. In addition, angiotensin II and adrenaline were infused.

2. It was observed that some of the cyclic nonapeptides resulted in high and prolonged increases in amounts of plasminogen activator in venous blood, in the following order, both for amplitude and duration: 1-desamino-6-monocarba-[8-d-arginine]-vasopressin > 1-desamino-[8-d-arginine]-vasopressin ≫ arginine-vasopressin = lysine-vasopressin > Nα-glycyl-glycyl-glycyl-lysine-vasopressin.

3. No plasminogen activator responses followed infusions of vasopressin tripeptide fragments, oxytocin, angiotension II, 1-desamino-[8-N-MeArg]-vasopressin or 9-desglycineamide-lysine-vasopressin octapeptide.

4. Mole for mole, the four most active substances were approximately two orders of ten more potent than adrenaline by amplitude comparison alone.

5. Intra-arterial adrenaline, in one-tenth the systemic dose, stimulated a release of plasminogen activator from the infused local vascular bed only, This did not occur with equivalent doses of arginine-vasopressin and 1-desamino-[8-d-arginine]-vasopressin.

6. It is concluded that plasminogen activator release arising from catecholamine-responding and vasopressin-responding receptors are both molecule-specific and different in anatomical location. The molecular structural requirements for triggering the latter hypothetical receptor type and potential clinical applications are discussed.
Changes in Absorptive and Peptide Hydrolase Activities in Rat Small Intestine after Administration of 5-Fluorouracil
Authors: Gardner M. L. G. , Samson R. R. , Heading R. C.
Published: August 2015

1. Glucose absorption, water absorption and dipeptide hydrolase activities have been determined in isolated rat small intestine at 1, 3, 5 and 21 days after a single intraperitoneal injection of 5-fluorouracil.

2. Absorption rates and enzyme activities were elevated 1 day after treatment, but were reduced to 40% of control values at 3 and 5 days. Changes were seen regardless of whether absorption was expressed per unit length or per unit dry weight of intestine.

3. There were highly significant positive correlations between glucose or water absorption rates and peptidase activities, especially in proximal jejunum. The most significant correlation was observed between water absorption rate and jejunal l-Leu-Gly hydrolase activity.

4. Malabsorption may account for some of the gastrointestinal side effects associated with treatment with 5-fluorouracil. Enzyme measurements may be useful as an index of intestinal function.
Effect of Oophorectomy and Calcium Deprivation on Bone Mass in the Rat
Authors: Hodgkinson A. , Aaron Jean E. , Horsman A. , McLachlan M. S. F. , Nordin B. E. C.
Published: August 2015

1. The effects of a low calcium diet and of oophorectomy, separately and together, on cortical and trabecular bone mass, have been examined in mature female rats.

2. Calcium deprivation caused a significant decrease of weight, cortical cross-sectional area and ratio of cortical to total area in the femur, it significantly reduced the volume of trabecular bone and increased the percentage of osteoid surface in the tail vertebrae, and in addition increased the urinary excretion of phosphate and, initially, of hydroxyproline.

3. Oophorectomy caused similar though smaller changes in trabecular bone and urine, whereas the effects of oophorectomy on cortical bone were greater on a low calcium intake than on a normal intake.

4. The ash weight of the femora, expressed as a percentage of the total dry weight, was unaffected by calcium deprivation or oophorectomy alone but was significantly reduced when the two occurred together.

5. The percentage of resorption surfaces in the vertebrae tended to increase on the low calcium diet and after oophorectomy on the normal diet but decreased after oophorectomy on a low calcium diet.

6. It is concluded that oophorectomy and calcium deficiency each reduce bone mass in the adult rat but the greatest effect is seen when they are combined.
Effects of Acute Acid–Base Alterations on Glutamine Metabolism and Renal Ammoniagenesis in the Dog
Authors: Fine A. , Bennett F. I. , Alleyne G. A. O.
Published: August 2015

1. The effects of acute acid—base alterations on renal ammonia production and glutamine metabolism were studied in anaesthetized dogs.

2. Plasma glutamine rose with acidosis and also when both Pco2 and plasma HCO−3 were raised isohydrically.

3. Blood urea fell when acidosis was induced with hydrochloric acid.

4. The renal production of ammonia per ml of renal blood flow was increased in acidosis, but this was independent of the amount of glutamine delivered to the kidney.

5. The results indicate that acute acidosis affects production of urea and glutamine and increases the capacity of the renal cells to extract glutamine from blood.
Purine Biosynthesis De Novo by Lymphocytes in Gout
Authors: Kamoun P. , Chanard J. , Brami M. , Funck-Brentano J. L.
Published: August 2015

1. A method of measurement in vitro of purine biosynthesis de novo in human circulating blood lymphocytes is proposed. The rate of early reactions of purine biosynthesis de novo was determined by the incorporation of [14C]formate into N-formyl glycinamide ribonucleotide when the subsequent reactions of the metabolic pathway were completely inhibited by the antibiotic azaserine.

2. Synthesis of 14C-labelled N-formyl glycinamide ribonucleotide by lymphocytes was measured in healthy control subjects and patients with primary gout or hyperuricaemia secondary to renal failure, with or without allopurinol therapy.

3. The average synthesis was higher in gouty patients without therapy than in control subjects, but the values obtained overlap the normal range. In secondary hyperuricaemia the synthesis was at same value as in control subjects.

4. These results are in agreement with the inconstant acceleration of purine biosynthesis de novo in gouty patients as seen by others with measurement of [14C]glycine incorporation into urinary uric acid.
Effect of Administration of Sar1-Ala8-Angiotensin II during the Development and Maintenance of Renal Hypertension in the Rat
Authors: Fernandes M. , Fiorentini R. , Onesti G. , Bellini G. , Gould A. B. , Hessan H. , Kim K. E. , Swartz C.
Published: August 2015

1. Sar1-Ala8-Angiotensin II (an angiotensin antagonist) was infused in rats during the development and maintenance of renal hypertension produced by aortic ligation between renal arteries.

2. In the early phase (5 and 12 days after ligation), infusion of the antagonist markedly decreased blood pressure although it did not reach normal pressures. Later (day 40) only a modest decrease in blood pressure was noted.

3. Removal of the small left kidney always decreased the blood pressure to normal pressures.

4. It is concluded that the renin—angiotensin system is the major pressor component in the initiation of this hypertension. Later, other factors of renal origin assume a pressor function.
Renal Function in Chronic Obstructive Jaundice: A Micropuncture Study in Rats
Authors: Allison Marjorie E. M. , Moss N. G. , Fraser Mary M. , Dobbie J. W. , Ryan C. J. , Kennedy A. C. , Blumgart L. H.
Published: August 2015

1. We have studied kidney structure and function in female Sprague—Dawley rats with chronic obstructive jaundice after bile-duct ligation and section and in age-matched sham-operated control animals.

2. High bile-duct ligation and section resulted in immediate hyperbilirubinaemia and progressive hepatomegaly with histological evidence of bile-duct proliferation and periportal inflammation and fibrosis.

3. Only 20% of the jaundiced animals developed ascites, but 42% became hypotensive and died during preparation for micropuncture.

4. In the surviving rats there was no significant change in blood pressure, whole-kidney glomerular filtration rate, single-nephron glomerular filtration rate or calculated glomerular capillary hydrostatic pressure from control animals. However, renal plasma flow was increased so that whole-kidney filtration fraction was low. These changes were largely reversed by choledochoduodenostomy.

5. Proximal tubular reabsorption in the jaundiced group was not different from control rats, although the inulin (urine/plasma) ratio was significantly reduced, indicating diminished reabsorption distal to the proximal convoluted tubule. Proximal intratubular hydrostatic pressure was significantly increased in some nephrons.

6. Electron microscopy of the glomeruli from the jaundiced animals revealed evidence of marked increase in activity of both epithelial and endothelial cells.

7. Rats who survive chronic obstructive jaundice for 3–4 weeks have changes in renal function and also structural changes suggestive of diminished glomerular permeability.
The Use of the Human Erythrocyte as a Model for Studying the Action of Diuretics on Sodium and Chloride Transport
Authors: Brooks B. A. , Lant A. F.
Published: August 2015

1. The Na+ and Cl− transport systems of human erythrocytes have been compared for their sensitivities to diuretics known to act in the ascending limb of Henle's loop. In addition, chemical analogues of ‘loop’ compounds and also diuretics which act in other areas of the nephron have been examined.

2. The Na+ transport system lacks specificity with respect to inhibition by ‘loop’ diuretics and also a related chemical analogue studied at equivalent concentrations.

3. The Cl− transport system is inhibited, at low concentrations, by diuretics known to act in the ascending limb of Henle's loop.

4. Erythrocyte Cl− transport offers a useful model with which to study the biochemical action of diuretics.
Lack of Effect of Blood-Volume Expansion on Short-Circuit Current across an Isolated Toad Skin Incorporated in the Circulation of a Rat
Authors: Querido D. , Isaacson L. C.
Published: August 2015

1. Evidence for the existence of ‘natriuretic hormone’ resides, in part, in the demonstration that blood volume expansion in the dog is followed by a transient fall in short-circuit current (SCC) across a frog skin incorporated within its circulation.

2. We have attempted to confirm this effect in the rat, with a toad skin (Xenopus laevis) incorporated within the circulation. The skins, bathed in whole rat blood, displayed low SCC; skins bathed in ‘mammalian’ Ringer solution displayed equally low SCC, but responded normally to pitressin or amiloride.

3. When volume expansion was induced in ten rats by infusion of equilibrated whole blood (28 ml/kg body weight) there was a brisk rise in systemic blood pressure, diuresis, natriuresis and kaliuresis.

4. This blood-volume expansion was without detectable effect on the SCC across the skins incorporated within the rats' circulations.
Urinary Kallikrein Excretion and Plasma Renin Activity in Patients with Essential Hypertension and Primary Aldosteronism
Authors: Lechi A. , Covi G. , Lechi C. , Corgnati A. , Arosio E. , Zatti M. , Scuro L. A.
Published: August 2015

1. The 24 h urinary excretion of kallikrein has been studied in 40 normotensive control subjects and in 74 age-matched patients with essential hypertension under similar conditions. By use of the renin-sodium index, hypertensive patients were divided into two subgroups: low-renin hypertension and normal-renin hypertension patients. Urinary kallikrein determinations were also obtained from six hypertensive patients with primary aldosteronism.

2. Urinary kallikrein was significantly lower both in patients with normal-renin and low-renin essential hypertension. Urinary kallikrein excretion was very high in the patients with primary aldosteronism.

3. In nine hypertensive patients β-adrenoreceptor-blocking therapy caused a significant decrease of plasma renin activity, but had no significant effect on urinary kallikrein excretion.

4. The results support the concept that low urinary kallikrein is likely to be a marker of essential hypertension. Under certain conditions its excretion is positively related to mineralocorticoid hormone concentrations but it is not primarily related to the renin-angiotensin system.
Determinants of High Blood Pressure in Salt-Deprived Renal Hypertensive Rats: Role of Changes in Plasma Volume, Extracellular Fluid Volume and Plasma Angiotensin II
Authors: Mourant A. J.
Published: August 2015

1. Rats with indwelling aortic and right atrial cannulae were maintained on a sodium-free diet before and after renal arterial constriction combined with contralateral nephrectomy. Control animals underwent the same protocol except that non-constricting clips were used.

2. Plasma volumes in the salt-deprived animals were lower than previously determined values in animals with free access to sodium. After clipping plasma volume increased in the hypertensive animals. Extracellular fluid volume was increased equally in both normotensive and hypertensive animals on the second postoperative day only.

3. Before clipping and contralateral nephrectomy plasma angiotensin II values were higher than normal. After the operation angiotensin II concentrations fell to normal over a period of 14 days without significant differences between experimental and control groups.

4. It is concluded that high blood pressure after clipping may be in part maintained by increases in plasma volume. However, the results strongly suggest that other renal mechanisms are likely to be of major pathogenic importance.
Effects of Concentration-Polarization on the Filtration of Proteins through Filters Constructed from Isolated Renal Basement Membrane
Authors: Cotter T. G. , Robinson G. B.
Published: August 2015

1. Filters comprising multiple layers of rabbit renal tubular basement membrane were constructed with conventional pressure filtration chambers. The effects of concentration-polarization on the behaviour of these filters was assessed by studying the filtration of proteins and of serum under turbulent (stirred) and unstirred conditions.

2. With stirring bovine serum albumin was effectively rejected by the filter barriers (σ = 0.95) but rejection was diminished (σ = 0.18) without stirring. The hydraulic permeability of the filters also fell without stirring.

3. In the presence of horse immunoglobulin G, a wholly rejected protein, the rejection of cytochrome c was increased and hydraulic flux was reduced.

4. Filtration studies of serum showed that serum protein was effectively rejected with stirring (σ > 0.999) but rejection diminished when stirring ceased (σ = 0.98). Albumin was the only protein detected in the filtrate with stirring but α- and β-globulins appeared when stirring ceased.

5. These results show that concentration-polarization markedly affects the behaviour of these basement membrane filters in vitro, since without stirring a polarization layer of rejected protein is formed, which reduces hydraulic permeability and results in increased protein permeation through the filter.
Parallel Changes between Lipoprotein Lipase Activating Capacity and Lipid Concentrations in the Serum of Rats and Ferrets during Development and Dietary Manipulation
Authors: Cryer A. , Heather M. Jones
Published: August 2015

1. The lipoprotein lipase activating capacity of serum from 5 to 22 day old rats and male ferrets fed on diets rich in either beef tallow or maize oil was significantly correlated with the triglyceride concentration in the serum.

2. These increases in activating capacity associated with increased serum triglyceride concentrations were similar to those reported for human serum.
Lack of Effect of Isometric Handgrip Exercise on the Responses of the Carotid Sinus Baroreceptor Reflex in Man
Authors: Ludbrook J. , Faris I. B. , Iannos J. , Jamieson G. G. , Russell W. J.
Published: August 2015

1. The change in arterial pressure and heart rate resulting from alteration of carotid sinus transmural pressure by a median −34 mmHg and +33 mmHg by means of a variable-pressure neck chamber was tested in seven male volunteer subjects, at rest and during exertion of 35, 45 and 65% of maximum voluntary handgrip.

2. During 60 s of 35 and 45%, and during 30 s of 65%, of maximal voluntary handgrip there was virtually no alteration of the response of blood pressure to alteration in carotid sinus transmural pressure.

3. The bradycardic response to increase in carotid sinus transmural pressure was reduced at various times after the commencement of handgrip at 45 and 65% of maximum voluntary contraction.

4. It is concluded that a reduction in arterial baroreceptor reflex sensitivity does not play an important role in the initiation of the increase in arterial blood pressure and heart rate caused by isometric exercise.

5. The hypothesis is advanced that some of the cardiovascular changes in exercise may result from elevation of the central ‘set point’ for blood pressure.
Problems in the Analysis of Dynamic Tracer Studies
Authors: Reeve J. , Veall N. , Wootton R.
Published: August 2015

The identity of the body is not dependent on the persistence of the same material particles … during life, by the process of eating and digesting, the body undergoes perpetual changes. St Thomas Aquinas, quoted by Hevesy (1962).
A Comparison of Methods for Measurement of Rectal Potential Difference in Man: Effects of Rectal Infusion of Amiloride
Authors: Mohamed F. , McSorley P. , Warren D. J.
Published: August 2015

1. Two methods for measurement of rectal potential difference in man were compared. A saline-filled catheter technique gave more reproducible results and was better tolerated by patients than the solid probe technique.

2. Infusion of amiloride at a concentration of 4 × 10−6 mol/l in saline produced a variable fall of potential difference in six normal subjects. Dose-response curves in two subjects showed that complete inhibition of rectal potential difference occurred at 4 × 10−5 mol/l and 4 × 10−6 mol/l respectively.

3. This finding provides additional evidence that rectal potential difference in man results from electrogenic ion transport across the mucosal epithelial cell.
Effect of Acute Ethanol Administration on Liver Oxidative Capacity in Rats
Authors: Videla L. A.
Published: August 2015

1. The administration of a single oral dose of 2, 3, 4 or 5 g of ethanol/kg (43.5, 65.2, 87.0 or 108.7 mmol/kg respectively) to rats increases the rate of oxygen consumption by liver slices from animals killed 24–48 h later.

2. The increase in the rate of hepatic respiration can be blocked by incubation in a medium containing ouabain, an inhibitor of the sodium pump, or in a calcium-free medium.

3. The enhancement of oxygen uptake caused by a single dose of ethanol can be abolished by adrenalectomy or by prior administration of the α-adrenergic blocking agent phentolamine, and is markedly less in thyroidectomized animals.

4. It is suggested that the effect which is elicited by acute ethanol administration on respiration by liver slices is mediated by adrenaline and by thyroid hormones, both of which appear to exert a calorigenic effect by activation of the sodium pump. The results are discussed in relation to the changes in liver oxidative capacity induced by chronic alcohol ingestion.
A Study In Vitro of the Sodium Pump in Fulminant Hepatic Failure
Authors: Alam A. N. , Poston Lucilla , Wilkinson S. P. , Golindano C. G. , Williams R.
Published: August 2015

1. The mechanism underlying the raised leucocyte sodium content in fulminant hepatic failure was studied by measurement of sodium fluxes, (Na+ + K+)-dependent adenosine triphosphatase activity, and leucocyte ATP content.

2. The rate constant for sodium efflux in the leucocytes was significantly reduced, and attributable to reduced activity of the enzyme (Na+ + K+)-ATPase. Leucocyte ATP content was not significantly different from that of control cells.

3. Incubation of cells from patients in the sera of normal subjects resulted in a reversal of these changes. Inhibition of the leucocyte sodium efflux rate constants and (Na+ + K+)-ATPase of normal cells was achieved by incubation in sera from patients.

4. We suggest that the raised sodium content of leucocytes in fulminant hepatic failure is attributable to a defective sodium pumping mechanism, possibly due to a circulating toxin.
Identification of a Delivery-Related Influence on Proximal Tubular Reabsorption during Expansion with Hyperoncotic Albumin in the Rat
Authors: Donohoe J. F. , Lefavour Gertrude S. , Cortell S. , Gennari F. J.
Published: August 2015

1. Proximal tubular fluid flow rate was deliberately reduced to control values in rats after acute volume expansion with hyperoncotic albumin, to determine if the depression of reabsorption by albumin-induced expansion could be uncovered by preventing the associated increase in filtrate delivery. Tubular fluid flow was reduced either by reducing renal perfusion pressures or by diverting fluid from early proximal tubular sites.

2. In the absence of controlled delivery, expansion with hyperoncotic albumin increased nephron filtration rate, reduced the TF/P inulin ratio, but had no effect on absolute reabsorptive rate. When proximal tubular flow rate was returned to control values by a simultaneous early collection, fractional reabsorption remained depressed. By contrast, when tubular flow was maintained at control values by reducing renal perfusion pressure, the large fall in fractional reabsorption was blocked.

3. The results indicate that expansion with hyperoncotic albumin depresses proximal tubular reabsorption independently of delivery rate into the proximal tubule, but that this effect can be reversed by a reduction in renal perfusion pressure. These observations unify the results of previous studies and indicate the presence of a delivery-related influence on proximal reabsorption. The inability to detect a reduction in absolute reabsorption when nephron filtration rate is increased during expansion with hyperoncotic albumin is probably due to the countervailing influence of increased delivery rate, which raised reabsorptive rate.
Adenine and Adenosine Metabolism in Intact Erythrocytes Deficient in Adenosine Monophosphate-Pyrophosphate Phosphoribosyltransferase: A Study of Two Families
Authors: Dean B. M. , Perrett D. , Simmonds H. Anne , Sahota A. , Van Acker K. J.
Published: August 2015

1. We have studied the metabolism of adenine and adenosine in intact erythrocytes from three children and four adults of two separate families. The children were homozygotes for a deficiency of AMP-pyrophosphate phosphoribosyltransferase (adenine phosphoribosyltransferase, EC 2.4.2.7), and the parents heterozygotes.

2. In this intact cell system at physiological concentrations of inorganic phosphate (Pi) and adenine heterozygote adenine phosphoribosyltransferase activity was normal, whereas at higher adenine concentrations (1.0–10 μmol/l) the four heterozygotes showed approximately 50% of control activity. At high concentrations of Pi (18 mmol/l) and adenine (10 μmol/l) and with extended incubation heterozygote activity was again indistinguishable from normal. Activity of the enzyme in homozygotes was negligible under all these conditions.

3. Formation of inosine 5′-monophosphate from [8-14C]hypoxanthine at high Pi concentrations was normal in both homozygotes and heterozygotes. Thus no abnormality of either of the enzymes IMP—pyrophosphate phosphoribosyltransferase (hypoxanthine phosphoribosyltransferase, EC 2.4.2.8) or phosphoribosyl pyrophosphate synthetase (ribose phosphate pyrophosphokinase, EC 2.7.6.1) was found.

4. To ascertain whether deficiency of adenine phosphoribosyltransferase was linked with enhanced conversion of adenosine into adenine nucleotides at the expense of its deamination pathways, the complete metabolism of [8-14C]adenosine was studied over the range 0.1–9.0 μmol/l. No such increase was observed for either heterozygotes or homozygotes.

5. Insignificant formation of either [8-14C]-adenine from [8-14C]adenosine or vice versa in the erythrocytes of homozygotes lacking adenine phosphoribosyltransferase but capable of forming hypoxathine from adenosine, supports the concept that adenine and adenosine are not directly interconvertible and do not utilize purine nucleoside phosphorylase (EC 2.4.2.1) in erythrocytes.

6. Measurement of erythrocyte nucleotide concentrations by high-performance liquid chromatography revealed no obvious abnormalities. ATP:ADP:AMP proportions were normal (approximately 10:1:0.1) and the total adenine nucleotide pool was at the lower limit of the normal range for both homozygotes and heterozygotes. These observations imply that deficiency of adenine phosphoribosyltransferase does not grossly affect adenine nucleotides synthesis in the erythrocyte.
Altered Activity of the Sodium-Potassium Pump in Arteries of Rats with Steroid Hypertension
Authors: Pamnani Motilal B. , Clough David L. , Haddy Francis J.
Published: August 2015

1. Ouabain-sensitive uptake of 86Rb, a measure of the Na+—K+ pump activity, was studied in tail arteries of rats made hypertensive with deoxycorticosterone and saline.

2. Decreased activity of the ouabain-sensitive Na+—K+ pump supports the hypothesis that the activity of Na+—K+ pump is suppressed in volume-expanded hypertension.
The Effects of Prednisolone on the Rat Enterocyte at a Subcellular Level
Authors: Batt R. M. , Wells G. , Peters T. J.
Published: August 2015

1. Enterocytes, isolated from the proximal jejunum and distal ileum of normal and prednisolone-treated rats, were homogenized and fractionated by isopycnic centrifugation on sucrose density gradients. The distributions of marker enzymes for the principal subcellular organelles, RNA and protein were determined and related to the activities per enterocyte.

2. In enterocytes from the jejunum and ileum of prednisolone-treated animals the activities of particulate brush-border enzymes and of both soluble and mitochondrial malate dehydrogenase were increased compared with those of the control system. The equilibrium density of the brush borders was enhanced in the prednisolone-treated jejunum. The modal densities of the other organelles were unaltered by prednisolone administration.

3. There was a large increase in the total RNA content of enterocytes from the jejunum and ileum of prednisolone-treated animals. This was predominantly associated with a distinct particulate component, indicative of a proliferation of the rough endoplasmic reticulum and consistent with an enhanced rate of protein synthesis.

4. Studies of latent brush-border enzyme activities, the mechanical fragility of isolated brush borders and electron microscopy suggest that steroid administration results in no marked alterations in the gross conformation of the brush- border membrane or in the orientation of the enzymes within the membrane.
Haemodynamics of Orally-Active Converting Enzyme Inhibitor (SQ 14225) in Hypertensive Patients
Authors: Cody R. J. , Tarazi R. C. , Bravo E. L. , Fouad F. M.
Published: August 2015

1. The haemodynamic effects of oral converting enzyme inhibitor (SQ 14225) were assessed in eight patients with severe essential or renovascular hypertension.

2. Mean arterial pressure fell (149 ± 5 to 127 ± 8 mmHg, P < 0.02), because of a fall in total peripheral resistance (6.9 ± 0.53 to 5.7 ± 0.40 kPa 1-1 s m2) without a significant change in cardiac index. Two of the eight patients were non-responders without pressure reduction or a haemodynamic change. Sodium restriction (10 mmol/day) while the same dose of SQ 14225 was continued further lowered arterial pressure (137 ± 8 to 111 ± 12 mmHg, P < 0.05) through further resistance reduction (6.5 ± 0.53 to 5.2 ± 0.40 kPa l−1 sm2, P < 0.05).

3. Haemodynamic responses to head-up tilt (increased heart rate and resistance, decreased cardiac index) were unaffected by SQ 14225 regardless of sodium intake.

4. The pattern of reduction in peripheral resistance, with unchanged cardiac index, was similar to that produced by vasodilators acting at both arteriolar and venular levels.
Evidence for an Hepatic Anti-Ketogenic Effect of Insulin in Man
Authors: Elkeles R. S. , Chalmers R. A. , Hambley J.
Published: August 2015

1. Infusion of a triglyceride emulsion (Intralipid) into overnight fasted normal subjects produced a rise in plasma free fatty acids (FFA) and blood ketones.

2. Glucose given orally 60 min after the start of the Intralipid infusion produced a sharp fall in blood ketones without much change in plasma FFA.

3. An infusion of glucagon given together with Intralipid did not alter the reduction in blood ketones produced by oral glucose in normal subjects.

4. Oral glucose given 60 min after the start of the Intralipid infusion in three insulin-requiring diabetic subjects produced no fall in blood ketones.

5. The results suggest that glucose prevents the increase in blood ketones after Intralipid through an increase in insulin secretion rather than through a suppression of glucagon or as a direct effect of glucose.

6. It is most likely that the effect of insulin is to inhibit hepatic ketogenesis.
Protective Effect of Prostaglandin [PGE2] in Glycerol-Induced Acute Renal Failure in Rats
Authors: Werb R. , Clark W. F. , Lindsay R. M. , Jones E. O. P. , Turnbull D. I. , Linton A. L.
Published: August 2015

1. Acute renal failure was induced in female Sprague—Dawley rats by the subcutaneous injection of glycerol.

2. Four groups of rats were studied; all animals received a glycerol challenge. Group A (control) were sham-operated only, group B received an infusion of sodium chloride solution (150 mmol/l; saline) for 24 h, group C received an infusion containing prostaglandin E2 (PGE2, 1.7 μmol/l) in saline and group D a solution containing PGE2 (3.4 μmol/l) in saline.

3. All rats were killed 48 h after glycerol challenge. The degree of renal impairment was assessed by serum creatinine concentration, which did not differ in sham-operated animals and the group receiving saline alone. The group of rats receiving the lower dose of PGE2 has a significantly lower mean serum creatinine concentration than the saline-infused control rats (P < 0.0025). Creatinine concentration was further lowered by the higher dose of PGE2 but there was not a significant difference in the number of rats showing severe tubular necrosis histologically.

4. The study demonstrates that intravenous infusion of prostaglandin E2 has a protective influence on glycerol-induced renal failure in the rat; the protection afforded may be due to the vasodilator effect of PGE2 and/or an effect on glomerular permeability.
Plasma Noradrenaline and Adrenaline and β-Adrenoreceptor Responsiveness in Renin Subgroups of Essential Hypertension
Authors: Bühler F. R. , Bertel O. , Kiowski D. W.
Published: August 2015

1. Plasma noradrenaline and adrenaline responses to graded exercise, reflecting sympathoneural and adrenal activity, were compared with β-adrenoreceptor-mediated renin and heart-rate responses in 33 patients with essential hypertension and either high (n = 13), normal (n = 15) or low (n = 5) renin—sodium index. β-adrenoreceptor responsiveness, was assessed using the chronotropic dose of isoprenaline which increased heart rate by 25 beats/min (CD25).

2. No significant differences in adrenaline were found among the renin subgroups either at rest or during equi-effective exercise stimulation, though values in the older low-renin patients tended to be lower.

3. Plasma noradrenaline at rest or exercise was similar in the renin subgroups. This contrasted with the normal exercise tachycardia and hyper-responsive renin in the high renin patients and the blunted exercise tachycardia and reduced renin response in the normal and low renin patients.

4. The CD25 of isoprenaline was 2·5 ± 2·2 sd μg/m2 in the high, 3·1 ± 4·4 in the normal and 4·5 ± 5·9 in the low renin group.

5. Older age and a longer history of hypertension may be associated with a transition from a high to a low and hyporesponsive renin—angiotensin system, with diminishing β-adrenoreceptor sensitivity. In the presence of deficient β-adrenoreceptors, a normal or slightly elevated sympathetic nerve activity may act predominantly via α-adrenoreceptor-mediated vasoconstriction, enhanced by structural vessel changes.
Noradrenaline Secretion by the Human Kidney
Authors: De Leeuw P. W. , Falke H. E. , Punt R. , Birkenhäger W. H.
Published: August 2015

1. In 20 subjects with uncomplicated essential hypertension, 10 of whom were on propranolol treatment, several blood samples were drawn simultaneously from the renal artery and vein after angiographic studies. In these samples we determined concentrations of noradrenaline, active renin, aldosterone and cortisol.

2. Renal blood flow was measured in all patients by Hippuran-clearance and xenon-washout.

3. Despite marked variations in the arteriovenous difference of noradrenaline, it was apparent in both groups that the kidney is able to release noradrenaline.

4. In the propranolol-treated group noradrenaline secretion by the kidney was enhanced when compared with untreated hypertensive patients.
The Kinetics of Plasma Noradrenaline in Normal and Hypertensive Subjects
Authors: Ghione S. , Palombo C. , Pellegrini M. , Fommei E. , Pilo A. , Donato L.
Published: August 2015

1. The kinetics of plasma noradrenaline have been determined in normal and essential hypertensive patients by intravenous injection of tritiated noradrenaline and serial mixed venous sampling.

2. The metabolic clearance rate of plasma noradrenaline in normal subjects was approximately 1·1 min−1 m−2, whereas in essential hypertensive patients it was significantly reduced to approximately 0·61 min−1 m−2.

3. Metabolic clearance rate was negatively correlated to mean arterial blood pressure and total peripheral resistances.

4. Particularly low values of metabolic clearance rate were found in two patients with congestive heart failure and one with phaeochromocytoma.

5. We propose that the access of plasma noradrenaline to the main removal mechanisms takes place in competition with the flow of unlabelled endogenous noradrenaline directly released by nerve endings. The slower removal of plasma noradrenaline in essential hypertension could then express a larger release of endogenous noradrenaline in this condition.
Activation of Inactive Plasma Renin: Evidence that Both Cryoactivation and Acid-Activation Work by Liberating a Neutral Serine Protease from Endogenous Inhibitors
Authors: Atlas Steven A. , Laragh John H. , Sealey Jean E.
Published: August 2015

1. We have found that ‘acid’-activation of inactive human plasma renin is a two-phase process. About 30% of activation occurs during dialysis to pH 3·3; the remaining 70% occurs at alkaline pH.

2. The ‘alkaline phase’ of activation has a pH optimum between 7·5 and 8·4. It is inhibited by unacidified plasma and by soya-bean or lima-bean trypsin inhibitors.

3. ‘Cryoactivation’ of inactive plasma renin, which occurs at −4°C and alkaline pH, is also inhibited by soya-bean or lima-bean trypsin inhibitors and by the serine protease inhibitors di-isopropylphosphorofluoridate and benzamidine.

4. Thus endogenous neutral serine proteases participate in the activation of inactive plasma renin in vitro. Their action is prevented in the circulation by inhibitors which are inactivated by acid or cold.
Different Responses of Active and Inactive Plasma Renin to Various Stimuli
Authors: Rumpf K. W. , Schächterle B. , Schmidt S. , Becker K. , Scheler F.
Published: August 2015

1. The response of active and inactive plasma renin to orthostasis and frusemide and to inhibition of prostaglandin synthesis by indomethacin was tested in normal human volunteers.

2. Active renin increased by orthostasis and frusemide and decreased by indomethacin. The latter also blunted the increase of active renin after stimuli.

3. Inactive renin was slightly increased by orthostasis, but was not significantly influenced by acute administration of frusemide or inhibition of prostaglandin synthesis by indomethacin.

4. The results show differences in the response of active and inactive renin to stimuli and suppression. Opposite changes of active and inactive renin were not observed in the experimental conditions studied.
Steroidogenic and Pressor Activity of Angiotensin Analogues in the Rat
Authors: Khairallah P. A. , Khosla M. C. , Bumpus F. M. , Tait J. F. , Tait S. A. S.
Published: August 2015

1. A classical 6 point assay in vitro for measuring aldosterone stimulating activity has been developed.

2. The steroidogenic potency of Ile5-angiotensin II was 62% of that given by Val5-angiotensin II. Ile5-angiotensin III (Des-Asp1-Ile5-angiotensin II) was likewise 50% as active as Val5-angiotensin III (Des-Asp1-Val5-angiotensin II). Similar results were obtained in the pressor and myotropic assays.

3. Ile5-angiotensin III and Val5-angiotensin III had only 7% and 16% respectively of the steroidogenic activity of Val5-angiotensin II.

4. Sar1-Ile5-angiotensin II was 2·3 times as potent as Val5-angiotensin II in aldosterone-stimulating activity. The corresponding activities of Me2-Gly1-angiotensin II, Pro1-angiotensin II and Pro31-angiotensin II were 71%, 15% and 3% of Val5-angiotensin II respectively.