bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of the Appearance of Radiolabelled Vitamin D3 and 25-Hydroxy-Vitamin D3 in the Chylomicron Fraction of Plasma after Oral Administration in Man
Authors: Compston Juliet E. , Merrett Anne L. , Hammett F. G. , Magill P.
Published: August 2015

1. The uptake of either orally administered [3H]vitamin D3 or 25-[3H]hydroxy-vitamin D3 into the chylomicron fraction of plasma was studied in 12 healthy male subjects.

2. The amount of [3H]vitamin D3 in the chylomicron fraction expressed as a percentage of the total plasma radioactivity was higher than that of 25-[3H]hydroxy-vitamin D3.

3. It is suggested that the mechanism of intestinal absorption of vitamin D and 25-hydroxy-vitamin D may differ in man, the absorption of 25-hydroxy-vitamin D possibly being less dependent on bile acids.
Evidence of Altered Copper Metabolism in Patients with Chronic Pancreatitis
Authors: Braganza Joan M. , Klass H. J. , Bell M. , Sturniolo G.
Published: August 2015

1. The copper content of duodenal juice obtained during secretin-pancreozymin tests has been compared in 12 healthy volunteers and 12 patients with chronic pancreatitis in whom normal gall-bladder function was confirmed by oral cholecystography. Of the 12 chronic pancreatitis patients 10 had not received any pancreatic supplement, one was on supplements for 10 years and one for 2 years.

2. In the control subjects the output of copper secretion into the duodenum displayed two phases: a sharp increase in the first 10 min after secretin [intravenous injection of 2 Crick-Harper-Raper units/kg of secretin (Boots)] and a second sharp rise in the first 10 min after pancreozymin [intravenous injection of 2 Crick-Harper-Raper units/kg of pancreozymin (Boots)].

3. In patients with chronic pancreatitis the pattern of copper secretion was similar to that of control subjects, but in the first 10 min after secretin the output of copper was significantly higher (P < 0.001). The post-secretin output of bilirubin was also higher in chronic pancreatitis (P < 0.02), but the volume of duodenal juice (P < 0.01), the outputs of bicarbonate (P < 0.001) and trypsin (0.05 < P < 0.1) were reduced compared with those of control subjects. The parallel increases in outputs of bilirubin and copper suggested that bile was the source of the increased copper in this group.

4. In the two chronic pancreatitis patients who received pancreatic supplements the post-secretin copper outputs were within normal limits. In a further group of five chronic pancreatitis patients who had been taking pancreatic supplements for many years the post-secretin copper output was not only less than in untreated chronic pancreatitis patients (P < 0.001), but less than in control subjects (P < 0.005). The output of bilirubin was similarly reduced (P < 0.01 and < 0.02 respectively).

5. Since bile is the major route for disposal of absorbed copper and since, under normal steady-state conditions, biliary copper excretion provides an index of copper absorption, our data suggest differences in long-term copper absorption between untreated and treated chronic pancreatitis patients. A component in pancreatic juice may therefore limit copper absorption under normal circumstances. Untreated chronic pancreatitis patients (who lack this factor) would absorb more copper, producing, over many years, an increase in hepatic and whole-body copper content. Long-term feeding of pancreatic supplements, by reducing copper absorption, would gradually deplete whole-body copper content.
Protein Degradation in Human Skeletal Muscle Tissue: The Effect of Insulin, Leucine, Amino Acids and Ions
Authors: Lundholm K. , Edström S. , Ekman L. , Karlberg I. , Walker P. , Scherstén T.
Published: August 2015

1. The protein degradation rate of human skeletal muscle was evaluated in vitro in isolated fibre bundles from the rectus abdominus muscle by measuring the tyrosine released from muscle tissue proteins. Protein metabolism in this semi-intact preparation was compared with that of the intact extensor digitorum longus muscles from rats under the same experimental conditions.

2. Protein balance was negative in both preparations, but protein synthesis and degradation were two to three times higher in the rat muscles. Tyrosine was released at a constant rate for at least 3 h of incubation independent of whether protein synthesis was inhibited or not. Disintegration of the muscle fibres more than doubled the tyrosine release rate. Human red gastrocnemius muscle showed 37% higher degradation rate compared with the predominantly white rectus abdominus muscle. The half-life of human skeletal muscle protein in vitro was estimated to be 20 days when calculated from the rate of tyrosine release.

3. The addition of leucine to the incubation medium decreased the rate of protein degradation, which was further decreased by the addition of other amino acids. Insulin did not influence the protein degradation rate during 2 h of incubation. This did not reflect a lack of sensitivity to insulin of the preparation, since protein synthesis responded to insulin. Calcium (5 mmol/l) stimulated and zinc (0.1 mmol/l) inhibited the protein degradation.

4. This experimental system may be suitable as an additional tool for evaluating protein degradation in human skeletal muscles.
Renin and Aldosterone Release during Sympathetic Stimulation in Tetraplegia
Authors: Mathias C. J. , Frankel H. L. , Davies I. B. , James V. H. T. , Peart W. S.
Published: August 2015

1. The effect of endogenous sympathetic stimulation (induced by urinary bladder stimulation) and intravenous infusion of noradrenaline and isoprenaline on blood pressure, heart rate and levels of plasma renin activity and plasma aldosterone were studied in six tetraplegic patients. Data from infusion studies were compared with data from six normal subjects studied in an identical manner.

2. Bladder stimulation in the tetraplegic patients caused a marked rise in blood pressure and fall in heart rate, but no change in plasma renin activity or plasma aldosterone.

3. Noradrenaline infusion resulted in an enhanced pressor response in the tetraplegic patients when compared with the normal subjects. Heart rate fell in both groups. Plasma renin activity and plasma aldosterone did not change in either group.

4. Isoprenaline infusion caused a fall in both systolic and diastolic blood pressure in the tetraplegic patients, unlike the normal subjects in whom there was a rise in systolic and a fall in diastolic blood pressure. Heart rate and plasma renin activity rose in both groups. Plasma aldosterone did not change in either group.

5. We conclude that in tetraplegic patients neither endogenous sympathetic stimulation by bladder stimulation nor infusion of noradrenaline raises plasma renin activity. Isoprenaline increases plasma renin activity to the same extent as in normal subjects. Renin release mechanisms in tetraplegic patients therefore do not appear to be hypersensitive to catecholamines. Plasma aldosterone is not influenced by any of the stimuli.
Activities of Hexokinase, Phosphofructokinase, Fructose Bisphosphatase and 2-Oxoglutarate Dehydrogenase in Muscle of Normal Subjects and Very Ill Surgical Patients
Authors: King R. F. G. J. , MacFie J. , Hill G.
Published: August 2015

1. The activities of hexokinase, phosphofructokinase, fructose bisphosphatase and 2-oxoglutarate dehydrogenase have been measured in the vastus lateralis and rectus abdominus muscle of normal human subjects and in very ill surgical patients.

2. The activities of these enzymes in the muscle of control subjects were similar to the pattern seen in the skeletal muscle of other mammals and lower vertebrates.

3. Fructose bisphosphatase and phosphofructokinase activities were significantly lower in the muscle of ill patients although the depression of the activity of fructose bisphosphatase was much greater than that of phosphofructokinase in both muscle types of ill patients.

4. The maximum rate of cycling in the fructose 6-phosphate-fructose 1,6-diphosphate cycle may be altered in the ill.

5. This decreased cycling may have a direct influence on the sensitivity of glycolysis to regulators such as the adenine nucleotides and may reduce the ability to maintain body temperature.

6. Increased glycogen synthesis in these muscles may indicate that the role of fructose bisphosphatase is unlikely to be solely in glycogen resynthesis.
Plasma Noradrenaline Concentration and α-Adrenoceptor-Mediated Vasoconstriction in Normotensive and Hypertensive Man
Authors: Kiowski W. , Bühler F. R. , Vanbrummelen P. , Amann F. W.
Published: August 2015

1. Plasma noradrenaline concentrations and blood pressure were measured in 45 patients with essential hypertension and 34 matched normotensive subjects. Plasma noradrenaline was similar in both groups, but in the hypertensive patients plasma noradrenaline correlated with blood pressure.

2. The increase in forearm flow in response to an intra-arterial infusion of phentolamine was determined in 12 of the hypertensive and 14 of the normotensive subjects to assess the α-adrenoceptor-mediated component of vascular resistance. Although the dilator response to phentolamine was similar in both groups, in the hypertensive patients it was correlated with the control plasma noradrenaline (r = 0.83, P<0.01) as well as the height of mean blood pressure (r = 0.73, P<0.01).

3. These results suggest that in hypertensive patients plasma noradrenaline can be a marker for both sympathetic activity and the α-adrenoceptor-mediated component of vascular resistance.
Serial Estimations of Carbon Monoxide Diffusing Capacity in Intrapulmonary Haemorrhage
Authors: Greening A. P. , Hughes J. M. B.
Published: August 2015

1. Serial estimations of the diffusing capacity for carbon monoxide, with a standard single-breath technique, were used to assist the monitoring of disease activity in patients at risk from intrapulmonary haemorrhage.

2. A reversible rise in diffusing capacity for carbon monoxide per unit alveolar volume (DLco/VA) of 50% or more above baseline values was detected on 61 occasions and in the diffusing capacity for carbon monoxide (DLco) alone on 45 occasions in 39 patients.

3. Concurrent with these rises in DLco/VA or DLco, two or more traditional indicators of intrapulmonary haemorrhage (haemoptysis, abrupt fall in haemoglobin concentration, chest X-ray opacities) were found on 47 occasions.

4. In the appropriate clinical context, acute reversible rises in DLco/VA or DLco reflect active intrapulmonary haemorrhage.
Deamination of Adenosine 5′-Phosphate and Adenosine as a Possible Source of Ammonia in Human and Bovine Parotid Glands
Authors: Bereznowski Z. , Stankiewicz A. , Makarewicz W.
Published: August 2015

1. The liberation of ammonia from adenosine 5′-phosphate (AMP) and adenosine and the release of inorganic phosphate from AMP were investigated in homogenates of bovine and human parotid glands.

2. Adenosine phosphate deaminase (AMP deaminase) was purified from bovine and human parotid glands. The enzyme preparations obtained were free from adenosine deaminase and 5′-nucleotidase activities.

3. AMP incubated with human parotid gland homogenate produced inosine 5′-phosphate, adenosine, inosine and ammonia. The amount of ammonia accumulating in the incubation mixture was equal to the sum of inosine 5′-phosphate plus inosine.

4. These results demonstrate the presence in human parotid of AMP deaminase and adenosine deaminase.
Effects of Salt and Water Depletion on the Early Phase of Hypertension in Goldblatt two-Kidney Hypertensive Dogs
Authors: Watson M. L. , McCormick J. , Thom A. , Whelpdale P. , Ungar A.
Published: August 2015

1. Hypertension was induced in dogs by partial occulsion of one renal artery, the opposite kidney remaining intact, and the changes in blood pressure, plasma renin activity, aldosterone and prostaglandin E (PGE) were monitored.

2. Two days after induction of hypertension, the retained sodium and water were removed by haemodialysis and the animals were then maintained on a low dietary intake of sodium for the following 7 days.

3. Removal of the accumulated sodium and water had no immediate effect on blood pressure, but during the ensuing 7 days there was a small decrease in blood pressure, which again increased after re-institution of a normal sodium intake.

4. Plasma renin activity and aldosterone increased during development of hypertension and remained elevated during the period of sodium restriction.

5. Sodium and water retained during the development of hypertension was not responsible for the elevated blood pressure.

6. The concentration of PGE in arterial plasma and renal venous plasma from the undamped kidney were unchanged during the study, although we have previously shown that in the absence of sodium depletion, PGE rises.

7. PGE released from the kidney may be important in mediating the excretion of sodium and water that is retained during the development of renal hypertension.
A Method for Assessing Responses of Small Arteries in Man: Effect of Physiological and Pharmacological Stimuli
Authors: Robinson B. F. , Dobbs R. J. , Kelsey C. R. , Saverymuttu S.
Published: August 2015

1. A method has been developed for estimating resistance to blood flow in the collateral arteries around the elbow. Arterial pressure is recorded continuously from the radial artery and blood flow in the forearm and hand is measured by venous occlusion plethysmography. The brachial artery is occluded for short periods, and the pressure drop across the collaterals and the flow through them are determined. From these observations an index of resistance can be calculated.

2. During 2 min occlusions of the brachial artery, collateral arterial resistance fell progressively to reach a level that was on average 45% lower than the initial resistance (P < 0.01).

3. There was an inverse relation between distending pressure in the collateral arteries and calculated resistance.

4. Ergotamine tartrate (0.25 mg intravenously) increased collateral resistance by an average of 135%. Glyceryl trinitrate (0.5 mg sublingually) reduced collateral resistance by an average of 45%. Hydrallazine and isoprenaline had an inconsistent dilator effect; the direct action of these drugs may have been offset by the reduction in distending pressure which they induced.

5. The elbow collateral arteries provide a useful model for studying physiological and pharmacological responses of small limb arteries in man.
The Disposition of Intravenous Potassium in Normal Man: The Role of Insulin
Authors: Sterns R. H. , Guzzo J. , Feig P. U.
Published: August 2015

1. Potassium infusion causes an increase in immunoreactive insulin levels in dogs, but either a small (30%) or no increase in humans. Since insulin stimulates the uptake of K+ by cells, a regulatory role for K+-induced insulin release has been postulated. To study the role of insulin in regulating cellular K+ uptake, six fasting normal volunteer subjects underwent two K+ infusions on separate days. Both infusions delivered 0.6 mmol h−1 kg−1 for 3 h. In one subject glucose was simultaneously infused at 0.67 mmol h−1 kg−1 (a rate known to increase peripheral insulin levels by 40–100%); the other infusion contained no glucose.

2. Plasma insulin levels did not increase during the glucose-free infusions. During glucose-containing infusions, insulin levels were 40% higher than those during glucose-free infusions. Despite this, neither urinary potassium excretion nor the increment in plasma K+ concentration or the calculated cellular K+ uptake differed significantly during the 3 h of glucose-free and glucose-containing infusions respectively.

3. These data do not support the view that potassium-induced insulin secretion regulates cellular potassium uptake within the physiological range of plasma K+ concentration.
Acute Effects of Captopril on Blood Pressure and Circulating Hormone Levels in Salt-Replete and Depleted Normal Subjects and Essential Hypertensive Patients
Authors: Millar J. A. , McGrath B. P. , Matthews P. G. , Johnston C. I.
Published: August 2015

1. The acute effects of a single oral dose of captopril on blood pressure, pulse rate and circulating levels of angiotensin I (ANG I), angiotensin II (ANG II), renin, bradykinin and catecholamines were studied in three groups: eight normal subjects, six salt-depleted normal subjects and 16 patients with essential hypertension.

2. Captopril treatment did not cause any significant fall in supine blood pressure in salt-replete normal subjects or patients with untreated essential hypertension but was associated with a fall in mean blood pressure from 85 ± 2 to 75 ± 2 mmHg in salt-depleted normal subjects and from 131 ± 7 to 117 ± 5 mmHg in patients with essential hypertension treated with diuretics. There was no change in pulse rate in any group.

3. Hormonal responses to captopril were qualitatively similar in the three groups and consisted of significant falls in ANG II with corresponding increases in ANG I and plasma renin concentration. The changes in plasma renin concentration and ANG I were greater in salt-depleted normal subjects (mean values at 90 min were 1140% and 990% of basal levels respectively) than in salt-replete normal subjects (410%, 190%) and were blunted in patients with essential hypertension (140%, 120%). Blood bradykinin, noradrenaline and adrenaline concentrations did not change after captopril in any group.

4. The parallel fall in blood pressure and ANG II levels in salt-depleted normal subjects is consistent with maintenance of blood pressure by increased levels of ANG II in sodium depletion.

5. The failure of captopril to reduce acutely blood pressure in patients with essential hypertension despite suppression of plasma ANG II and without change in circulating bradykinin confirms that the renin-angiotensin system does not play a primary role in essential hypertension.
[Asp1, Val5] Angiotensin-(1–8)octapeptide Does Not Stimulate Aldosterone Secretion in Sodium-Depleted Sheep
Authors: Scoggins B. A. , McDougall J. G. , Butkus Aldona , Coghlan J. P. , Denton D. A. , Hardy K. J. , Wright R. D.
Published: August 2015

1. To test the hypothesis that [Asp1,Val5]-angiotensin-(1–8)octapeptide ([Asp1,Val5]ANG II) is a more potent agonist to aldosterone secretion in the sodium-depleted animal than is [Asn1,Val5]angiotensin-(1–8)octapeptide ([Asn1,Val5]ANG II), local adrenal arterial infusion of the two peptides has been carried out in sheep with cervical adrenal autotransplants.

2. Neither [Asp1,Val5]ANG II nor [Asn1,Vak5]-ANG II further stimulated the increased level of aldosterone secretion in conscious moderately sodium-depleted sheep. Greater sodium deficiency further increased aldosterone secretion.

3. The conclusion of Campbell, Schmitz & Itskovitz [Clinical Science (1979), 56, 325–333] that the free acid form of angiotensin II was a more potent agonist of aldosterone secretion than was the amide form under conditions of reduced sodium status is not supported by studies in sodium-depleted sheep.
Arterial Plasma Histamine after Exercise in Normal Individuals and in Patients with Exercise-Induced Asthma
Authors: Hartley J. P. R. , Charles T. J. , Monie R. D. H. , Seaton A. , Taylor W. H. , Westwood A. , Williams J. D.
Published: August 2015

1. Arterial plasma histamine concentrations, forced expiratory volume in 1.0 s (FEV1.0) and peak expiratory flow rate were determined in nine patients with exercise-induced asthma and in five control subjects before and after 8 min of cycle-ergometer exercise.

2. In the controls neither FEV1.0 nor peak expiratory flow rate fell by more than 5% in any individual during the 30 min postexercise period. The asthmatic patients all experienced a fall in FEV1.0 or peak expiratory flow rate, or both, of 15% or more in the period 5–20 min after completion of the exercise.

3. There was no difference between the control subjects and the asthmatic patients in the plasma histamine response to exercise. In both groups there was an insignificant rise of about 40% during exercise, although the initial levels were higher in the asthmatic patients.

4. The mean plasma histamine peak of the asthmatic patients preceded the mean maximal fall of FEV1.0 and peak expiratory flow rate by approximately 15 min. However, no positive correlation was found between rise in, or peak, plasma histamine levels and decrease in lung function.

5. Three non-atopic asthmatic patients had a significantly higher mean plasma histamine concentration during exercise than had the atopic subjects.

6. A strong positive correlation in asthmatic patients, and asthmatic and control subjects together was found between age and mean postexercise plasma histamine concentrations.

7. The results do not support a direct role for histamine in the production of exercise-induced asthma.
Respiratory Activity of the Vocal Cords in Normal Subjects and Patients with Airflow Obstruction: An Electromyographic Study
Authors: Payne Julia , Higenbottam T. , Guindi G.
Published: August 2015

1. A surface electrode was used to record electromyographic activity of the posterior crico-arytenoid muscle during breathing in normal subjects and patients with airflow obstruction.

2. Phasic activity of the posterior crico-arytenoid muscle was demonstrated. This was present on inspiration and absent on expiration.

3. Phasic inspiratory activity in normal subjects was present only during periods of voluntary hyperventilation, increasing with tidal volume, whereas in patients with airflow obstruction inspiratory activity was present even during resting breathing and failed to increase further during voluntary hyperventilation.

4. The posterior crico-arytenoid muscle may be considered as an inspiratory muscle acting analogously to other accessory respiratory muscles.
Haemodynamics, Plasma Noradrenaline and Plasma Renin in Hypertensive and Normotensive Teenagers
Authors: Hofman A. , Roelandt J. T. R. C. , Boomsma F. , Schalekamp M. A. D. H. , Valkenburg H. A.
Published: August 2015

1. Plasma noradrenaline, active and inactive plasma renin, cardiac index and total peripheral vascular resistance were studied in 41 subjects, initially aged 10–19 years, who were followed up for at least 2 years after a blood pressure reading of 140 and/or 90 mmHg or more (initial hypertensives) and in 41 normotensive control subjects selected from the same population and matched for age, sex and body-mass index.

2. The initial hypertensive subjects had a lower mean cardiac index (3.63 ± sd 0.83 vs 4.00 ± 0.89 litre min−1 m−2), a higher mean total peripheral resistance (26.8 ± 5.7 vs 22.8 ± 5.5 units) and a higher mean plasma noradrenaline concentration (336 ± 146 vs 281 ± 126 pg/ml) than the control subjects.

3. Mean plasma noradrenaline concentration was higher in initial hypertensive subjects with a high active renin concentration than in those with a normal renin concentration (442 ± 70 vs 324 ± 100 pg/ml).

4. A weight-adjusted standardized regression coefficient of 0.77 between active plasma renin concentration and left ventricular mass was found in normotensive control subjects.

5. These findings are at variance with the existence of a hyperkinetic phase in young hypertensive subjects and suggest that sympathetic overactivity may be related to early essential hypertension through increase of peripheral vascular resistance.
Evaluation of the Mineralocorticoid Activity of 18-Hydroxycorticosterone
Authors: Huston G. , Martin V. I. , Al-Dujaili E. A. S. , Edwards C. R. W.
Published: August 2015

1. The mineralocorticoid activity of 18-hydroxycorticosterone (18-OH-B) has been compared with that of aldosterone by using human bioassay in vivo with measurement of rectal potential difference and urinary log 10 Na+/K+ ratio.

2. A log-linear relationship was found between maximum change in rectal potential difference and increasing doses of aldosterone.

3. No mineralocorticoid activity could be demonstrated after an intravenous bolus and infusion of 18-OH-B.

4. The half-life of clearance of 18-OH-B was measured in three subjects and found to be 28, 48 and 24 min.
Effects of a Low-Salt Diet and of Acute Salt Loading on Blood Pressure and Intralymphocytic Sodium Concentration in Young Subjects with Borderline Hypertension
Authors: Costa F. V. , Ambrosioni E. , Montebugnoli L. , Paccaloni L. , Vasconi L. , Magnani B.
Published: August 2015

1. Three groups of young patients with borderline hypertension were studied for a 12 months period. The first was on a free sodium diet while the second was on a low-salt diet. The third group of patients underwent acute salt loading.

2. After 12 months the group on free diet showed a significant increase of intralymphocytic sodium but no change in blood pressure was noted. Five patients who were re-checked after 24 months also had a significant increase in blood pressure.

3. Patients treated with a low-salt diet showed a significant decrease of both intralymphocytic sodium concentration and blood pressure.

4. After acute salt loading, borderline subjects with high intralymphocytic sodium showed a significant greater natriuresis whereas intralymphocytic sodium increased only in those subjects in whom it was initially normal.
Effect of Sodium Intake on Angiotensin-Converting Enzyme Activity of Aorta in Rats
Authors: Mizuno Kenji , Hata Shunichi , Fukuchi Soitsu
Published: August 2015

1. The effect of sodium intake on angiotensin-converting enzyme activity in subcellular fractions of aorta (homogenate, mitochondria, microsomes and supernatant) was studied in normotensive and spontaneously hypertensive rats.

2. Angiotensin-converting enzyme activity was extremely high in the supernatant fraction in normotensive and spontaneously hypertensive rats.

3. Total converting enzyme activity in spontaneously hypertensive rats was 34% higher than that in normotensive rats.

4. Increased sodium intake resulted in a marked reduction, almost to zero, of converting enzyme activity in each fraction of aorta in normotensive and spontaneously hypertensive rats.

5. Converting enzyme, widely distributed in subcellular fractions of the aorta, may play a possible rôle in the local control of vascular tone. It is likely that sodium intake inhibits production of the enzyme in vascular tissue.
Captopril Attenuates Adrenergic Vasoconstriction in Rat Mesenteric Arteries by Angiotensin-Dependent and -Independent Mechanisms
Authors: Collis M. G. , Keddie J. R.
Published: August 2015

1. Angiotensin-converting enzyme inhibitors can attenuate reflex sympathetic vasoconstriction in vivo. We have investigated the effects of captopril (SQ 14 225) on adrenergic vasoconstrictor mechanisms in isolated, Krebs-Ringer solution perfused, rat mesenteric arteries.

2. Low concentrations of captopril (2 × 10−6 mol/l) did not alter the vasoconstrictor response evoked by sympathetic nerve stimulation.

3. Exogenous angiotensin I and II did not have a direct vasoconstrictor effect, but caused dose-related increases in the amplitude of responses induced by nerve stimulation.

4. The potentiating effect of angiotensin I was antagonized by captopril (6.7 × 10−8–2 × 10−6 mol/l) and by saralasin (10−8 mol/l). The potentiating effect of angiotensin II was antagonized by saralasin only.

5. In the absence of exogenous peptides high concentrations of captopril (1 × 10−4–3 × 10−4 mol/l) antagonized vasoconstrictor responses evoked by sympathetic nerve stimulation and exogenous noradrenaline, but not those evoked by potassium chloride.

6. These results indicate that captopril can have two types of inhibitory effect at the adrenergic neuro-effector junction. High concentrations antagonize responses to noradrenaline and nerve stimulation. This effect is independent of peptide hormones and is unlikely to occur in vivo. Lower concentrations block the local vascular conversion of angiotensin I into II.

As angiotensin II is an important peripheral amplifier of adrenergic vasoconstriction, this effect will also reduce sympathetic vasoconstrictor tone. This latter interaction could explain the inhibitory effect of converting enzyme inhibitors on sympathetic reflexes.
Increased Sodium Content and Altered Sodium Transport in Thymocytes of Spontaneously Hypertensive Rats
Authors: Jones R. B. , Patrick J. , Hilton P. J.
Published: August 2015

1. The intracellular sodium content and the sodium efflux rate constant have been determined in vitro in thymocytes derived from the Okamato-Aoki strain of spontaneously hypertensive rats.

2. A strong positive correlation between the systolic blood pressure and the sodium content of thymocytes was observed (r = 0.59, n = 39, P < 0.001).

3. The rate constant for total sodium efflux was negatively correlated with systolic blood pressure (r = −0.43, n = 45, P < 0.005) and this was due to a fall in the ouabain-sensitive component of sodium efflux.

4. Sodium efflux, influx and the thymocyte potassium content were not related to the blood pressure.
Relationship between Altered Na+–K+ Cotransport and Na+–Li+ Countertransport in the Erythrocytes of ‘essential’ Hypertensive Patients
Authors: Cusi D. , Barlassina C. , Ferrandi M. , Palazzi P. , Celega E. , Bianchi G.
Published: August 2015

1. The maximal rate of activity of sodium extrusion by the sodium pump, Na+—K+ outward cotransport, passive permeability to sodium and potassium, Na+—Li+ countertransport, and passive permeability to lithium were measured in 45 essential hypertensive patients, 24 young normotensive subjects with at least one hypertensive parent and 24 normotensive subjects with both parents normotensive.

2. The maximal rate of activity of the sodium pump and the rate constants for passive permeability to sodium, potassium and lithium were similar in the three groups.

3. The mean value for Na+—K+ outward cotransport was significantly lower and that for Na+—Li+ countertransport significantly higher in the hypertensive patients than in the normotensive subjects without a family history of hypertension, but there was a great overlap between individual values. The offspring of hypertensive parents had intermediate values.

4. A highly significant positive correlation existed between Na+—K+ cotransport and Na+—Li+ countertransport both in the normotensive and in the hypertensive subjects, indicating that in the latter there were some with high Na+—Li+ countertransport and others with low Na+—K+ cotransport.

5. In nine hypertensive families studied, if an alteration of the transport system was detected in a hypertensive propositus, the same type of alteration was also found in his still normotensive offspring, thus indicating a familial tendency for the alteration to occur.
Effect of Acute and Chronic Salt Loading on Erythrocyte 22Na Efflux in Males with Essential Hypertension
Authors: Myers J. B. , Fitzgibbon W. R. , Morgan T. O.
Published: August 2015

1. Present results confirm our previous work which showed that a sodium intake over 3 mmol day−1 kg−1 decreased the total erythrocyte efflux rate constant in untreated males with essential hypertension.

2. The infusion of saline (2.25 mmol of Na+/kg) over 30 min decreased the efflux rate constant.

3. The change after chronic sodium loading and the intravenous infusion of saline is in the ouabain-sensitive component (ouabain-sensitive Na+, K+ ATPase pump activity) of total efflux.

4. The reduction in efflux by an acute sodium load occurred only when chronic sodium intake was low.

5. Posture did not affect the efflux rate constant whether sodium intake was high or low.

6. The reduction in efflux after chronic ingestion and acute administration of sodium occurred only when erythrocytes were incubated in plasma. It did not occur in artificial medium, which suggested that a plasma factor mediated the effect of added sodium on cell sodium efflux.

7. The effect of sodium on cell sodium transport by a plasma factor with ouabain-like properties (which may be a natriuretic hormone) constitutes a regulatory system. This system, the sodium-ouabain-vsensitive cell sodium-transport pathway system, has important implications for the understanding of blood pressure control and sodium homeostasis.
Intracellular Cation Activities and Concentrations in Spontaneously Hypertensive and Normotensive Rats
Authors: Zidek W. , Vetter H. , Zumkley H. , Losse H.
Published: August 2015

1. The intracellular concentrations of Na+, K+ and Ca2+ were measured in the erythrocytes of spontaneously hypertensive rats and normotensive Wistar rats.

2. The intracellular Na+ concentration in hypertensive rats was slightly elevated at 3.16 ± 0.25 compared with 2.85 ± 0.35 mmol/l (P ≈ 0.05) and intracellular Na+ activity was markedly increased in hypertensive rats.

3. Intracellular Ca2+ activity was 7519 ± 28 990 nmol/l of free water in hypertensive rats compared with 123 ± 98 in controls (P < 0.01).

4. The cytoplasm of hypertensive animals did not buffer Ca2+ as effectively as that of normal animals.

5. It is concluded that a decreased binding capacity of intracellular macromolecules for Na+ and Ca2+ may explain the disturbances of intracellular electrolyte composition in spontaneously hypertensive rats.
Carotid Sinus Reflex Control of Renin Release in Hypertensive Subjects with High Renin Secretion
Authors: Mancia G. , Ferrari A. , Leonetti G. , Gregorini Luisa , Terzoli Laura , Parati G. , Bianchini C. , Zanchetti A.
Published: August 2015

1. Carotid baroreceptor manipulation (neckchamber technique) and passive head-up tilting were used in ten patients with renovascular hypertension and in five subjects with essential hypertension under diuretic treatment to study reflex control of renin secretion” at high basal-renin production rates.

2. Reflex effects of carotid baroreceptor manipulation on renin secretion were only minor. During baroreceptor deactivation there was a moderate increase in mean arterial pressure, but an inconsistent change in the renal venous—arterial difference in plasma renin activity (PRA).

3. During baroreceptor stimulation there was a modest fall in mean arterial pressure and a marked rise in the renal venous—arterial difference in PRA. This was opposite to the fall which might have been predicted as a result of the sympathetic depressor influence of the baroreceptor stimulus. Conversely, tilting increased the venous—arterial PRA difference by about 200%.

4. It is concluded that when renin production rate is high carotid baroreceptors exert little control over renin release, just as when renin production is low. Reflex control of renin, however, is very active in subjects with a high renin production, probably due to receptors in the cardiopulmonary region.
Plasma Angiotensin II Concentration Regulates Vascular but Not Adrenal Responsiveness to Restriction of Sodium Intake in Normal Man
Authors: Dawson-Hughes Bess F. , Moore T. J. , Dluhy R. G. , Hollenberg N. K. , Williams G. H.
Published: August 2015

1. Sodium restriction increases adrenal and decreases vascular sensitivity to angiotensin II (ANG II). These responses may be mediated either by the circulating level of ANG II or other mechanisms also modified by a change in sodium balance. To assess the importance of the ANG II level, captopril, an oral converting enzyme inhibitor, was used to lower the plasma ANG II level to the sodium-loaded range while maintaining subjects in low sodium balance.

2. Normal volunteer subjects received an infusion of ANG II in increasing doses in three states: high sodium intake, low sodium intake and low sodium intake after pretreatment with captopril.

3. Basal levels of ANG II on high-sodium diet and low-sodium diet plus captopril were similar. In the ANG II infusion studies the slope of the aldosterone—ANG II regression line on low sodium intake was significantly steeper than that on high sodium intake. After the addition of captopril the slope was not decreased, indicating that the endogenous ANG II concentration is not necessary to maintain adrenal sensitivity during sodium restriction.

4. In the ANG II infusion studies the slope of the mean blood pressure—ANG II regression line on high sodium intake was significantly steeper than that on low sodium intake. The addition of captopril to sodium-restricted subjects caused the slope of the regression relationship to increase significantly, consistent with an enhanced vascular responsiveness when endogenous ANG II levels were lowered. However, the slope on low sodium plus captopril did not increase to the level of subjects on a high-sodium diet, suggesting that factors in addition to the circulating ANG II level are also important in regulating the vascular responsiveness to ANG II.
Calcium Efflux and Steroid Output from Superfused Rat Adrenal Cells: Effects of Potassium, Adrenocorticotropic Hormone, 5-Hydroxytryptamine, Adenosine 3′:5′-Cyclic Monophosphate and Angiotensins II and III
Authors: Williams B. C. , McDougall J. G. , Tait J. F. , Tait S. A. S.
Published: August 2015

1. The efflux of 45Ca from prelabelled dispersed rat adrenal capsular and decapsulated cell preparations was studied with a column superfusion system. Corticosterone and aldosterone outputs were measured by direct and extraction radioimmunoassays.

2. The stimulants potassium, adrenocorticotropic hormone (ACTH), serotonin and adenosine 3′:5′-cyclic monophosphate (cyclic AMP), at concentrations which gave marked increases in steroid output, had no significant effect on the rate of 45Ca efflux from capsular cell preparations (mainly zona glomerulosa).

3. ACTH, at a concentration which stimulated steriodogenesis similarly, did not alter the rate of 45Ca efflux from decapsulated cell preparations (zona fasciculata/reticularis).

4. [Asp1, Val5]Angiotensin II caused dose-dependent increases in the rate of 45Ca efflux from capsular cells which correlated with corresponding increases in steroid output, but had no effect either on 45Ca efflux or corticosterone output in decapsulated cell preparations. [desAsp1,Ile5]Angiotensin II (angiotensin III) caused similar dose-dependent increases in 45Ca efflux from capsular cells, which correlated with its effects on steroidogenesis, but was less potent in both respects than angiotensin II.

5. Lowered extracellular calcium caused a very marked and rapid increase in 45Ca efflux in capsular-cell preparations, which was not significantly modified by raising the extracellular potassium concentration, although stimulation of steriodogenesis was observed.

6. These findings suggest that in zona glomerulosa cells the stimulants potassium, ACTH, serotonin and cyclic AMP are not coupled to changes in calcium transport indicated by alterations in calcium efflux, whereas angiotensins II and III, the only stimulants examined which do not increase cyclic AMP in these cell preparations, appear to act through a calcium-mediated control mechanism. In zona fasciculata/reticularis cell preparations ACTH does not appear to be coupled to such changes in calcium transport.
Reduced Airway Vagal Tone in Diabetic Patients with Autonomic Neuropathy
Authors: Douglas N. J. , Campbell I. W. , Ewing D. J. , Clarke B. F. , Flenley D. C.
Published: August 2015

1. Forced expiratory flow rates and specific airways conductance were measured before and after the inhalation of the atropine-like drug ipratropium bromide in 11 diabetic patients with autonomic neuropathy and a control group of 11 diabetic patients without autonomic neuropathy. Respiratory muscle function was assessed by recording maximal inspiratory and expiratory mouth pressures.

2. There was no difference between the two groups of diabetic patients in airway calibre before ipratropium bromide or in maximal mouth pressures.

3. Bronchodilatation after ipratropium bromide was greater in the control group than in the autonomic neuropathy group of patients.

4. It is concluded that, despite the lack of clinical evidence of respiratory involvement, patients with diabetic autonomic neuropathy have reduced airway vagal tone.
On the Extravascular Pool of Low-Density Lipoprotein in Rat Liver
Authors: Sigurdsson G. , Shames D. M. , Havel R. J.
Published: August 2015

1. The mass of the extravascular pool of low-density lipoprotein (LDL) in liver was measured in rats injected intravenously with radioiodinated LDL by determining the radioactive iodine remaining in the extravascular tissues of liver and in plasma when the hepatic intravascular and extravascular radioactive iodine had equilibrated (equilibrium-time method).

2. The mass of the extravascular pool of LDL in the liver was about 6% of the total intravascular pool. Total extravascular pool of LDL in eight rats, obtained by multicompartmental analysis of the time-curve of disappearance of radioiodinated LDL from blood plasma, was 43 ± 15% (mean ± sd) of the intravascular pool.

3. Hence the hepatic extravascular pool comprises only about 14% of the total extravascular pool of LDL in the rat.
Associations between Sex Hormones, Thyroid Hormones and Lipoproteins
Authors: Heller R. F. , Miller N. E. , Lewis B. , Vermeulen A. , Fairney Angela , James V. H. T. , Swan A. V.
Published: August 2015

1. A study of 150 middle-aged male industrial employees has shown significant positive correlations between plasma levels of high-density-lipoprotein (HDL) cholesterol and both serum testosterone and alcohol intake, and significant negative correlations between HDL cholesterol and both serum thyroxine and obesity. These associations persist when examined by multiple linear regression, indicating their independence.

2. Significant positive correlations are also shown between plasma triglyceride levels and both obesity and serum thyrotropic hormone (TSH) levels.

3. There are no evident relationships between serum oestrone or oestradiol and either HDL cholesterol or triglyceride levels, nor between any of the hormones and either total or low-density-lipoprotein (LDL) cholesterol.

4. Because of the potential importance in relation to coronary heart disease prevention, further studies are needed to try and understand the mechanisms of the associations between HDL cholesterol and obesity, alcohol intake and thyroid and sex hormone levels.
Production of Collagenase and Inhibitor (Timp) by Normal, Rheumatoid and Osteoarthritic Synovium In Vitro: Effects of Hydrocortisone and Indomethacin
Authors: McGuire Mary B. , Murphy Gillian , Reynolds J. J. , Russell R. G. G.
Published: August 2015

1. the amounts of latent and active collagenase and of collagenase inhibitor (TIMP) produced by two normal, three rheumatoid and two osteoarthritic synovial specimens in culture were compared. Normal synovia produced TIMP, but little latent enzyme. Rheumatoid synovia produced higher levels of total collagenase activity than normal, of which up to 50% in one sample was present in the medium in an active form, whereas no specific inhibitory activity due to TIMP was detectable. the amounts of collagenase and TIMP produced by osteoarthritic synovia were more variable and appeared to reflect the degree of inflammation in the tissue at the time of initiating the cultures.

2. Concentrations of TIMP were usually higher in the culture media of normal, rheumatoid and osteoarthritic synovia when hydrocortisone was present. Correspondingly, amounts of total collagenase were reduced. Production of prostaglandin E (PGE) were inhibited in a dose-dependent manner by hydrocortisone.

3. Indomethacin had no consistent effect on the production of TIMP by rheumatoid and osteoarthritic synovia, although it tended to depress production of collagenase. the production of TIMP by normal synovia was depressed by indomethacin. No PGE was detectable in the media when indomethacin was present.

4. These results are consistent with those from previous animal studies, and we conclude that the balance between production of collagenase and TIMP may be critical in determining the extent of the destructive processes in arthritis. the ability of hydrocortisone to suppress production of collagenase and to increase free TIMP concentration, as well as to inhibit synthesis of prostaglandin, may explain in part how the drug exerts its therapeutic effects in patients with rheumatoid arthritis.
Characterization of Collagenase, other Metallo-Proteinases and An Inhibitor (Timp) Produced by Human Synovium and Cartilage in Culture
Authors: Murphy Gillian , McGuire Mary B. , Russell R. G. G. , Reynolds J. J.
Published: August 2015

1. Explants of human synovium from normal, rheumatoid and osteoarthritic subjects produced proteinases in culture that could degrade connective tissue macromolecules at neutral pH.

2. the proteinases detected in the media were predominantly of the class requiring metal ions for activity, and occurred in either partially or wholly latent forms. Activation could be achieved by treatment with either trypsin or the organomercurial, 4-aminophenylmercuric acetate.

3. Explants of both normal and osteoarthritic synovium produced an inhibitor of collagenase in the early days of culture, similar to that previously described for rabbit tissues. in contrast, no free inhibitor could be detected in the media of rheumatoid synovial cultures.

4. Explants of normal human articular cartilage produced latent collagenase and free inhibitor in culture.

5. These findings suggest that the activity of tissue-derived metallo-proteinases may be controlled by locally synthesized inhibitors, by mechanisms analogous to those already described for rabbit model systems. Changes in the synthesis and degradation of inhibitor could be important in human diseases in which destruction of connective tissue is a prominent feature.
Effect of Dihydroxylated Metabolites of Vitamin D3 on Calcium Absorption in Uraemic Man
Authors: Muirhead N. , Catto G. R. D. , Gvozdanovic S. , Gvozdanovic D. , Edward N.
Published: August 2015

1. Peak 47Ca absorption and 7 day 47Ca retention were measured by a whole-body radioactivity counting technique in 10 haemodialysis patients before and after treatment with 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] and 24,25-dihydroxycholecalciferol [24,25-(OH)2D3].

2. Before treatment all patients had low peak 47Ca absorption and 7 day 47Ca retention.

3. After treatment with 1,25-(OH)2D3 (0.25-1 μg/day for 4–12 months) peak 47Ca absorption and 7 day 47Ca retention returned to normal.

4. After treatment with 24,25-(OH)2D3 (2 μg/day for 4–12 months) peak 47Ca absorption and 7 day 47Ca retention remained at pre-treatment levels.

5. It is concluded that physiological doses of 24,25-(OH)2D3 have no effect on calcium absorption or retention in uraemic man.
Effect of Renal Failure on Erythrocyte Purine Nucleotide, Nucleoside and Base Concentrations and Some Related Enzyme Activities
Authors: Mansell M. A. , Allsop J. , North M. E. , Simmonds R. J. , Harkness R. A. , Watts R. W. E.
Published: August 2015

1. We have studied purine metabolism in renal failure using high-pressure liquid chromatography to determine metabolite concentrations in erythrocytes and plasma, and microradiochemical assays of enzyme activity in erythrocytes.

2. the mean activities of some of the enzymes involved in purine metabolism were raised in renal failure. Significant elevations of adenylate kinase (EC 2.7.4.3), purine nucleoside phosphorylase (EC 2.4.2.1), hypoxanthine phosphoribosyltransferase (EC 2.4.2.8) and adenosine deaminase (EC 3.5.4.4) but not of adenine phosphoribosyltransferase (EC 2.4.2.7) and ribosephosphate pyrophosphokinase (phosphoribosylpyrophosphate synthetase; EC 2.7.6.1) activities were demonstrated. However, there was an overlap between results from patients with renal failure and normal (control) subjects. Erythrocyte phosphoribosylpyrophosphate levels were also unchanged.

3. Erythrocyte nucleotide concentrations especially those of inosine were raised in renal failure.

4. the plasma inosine was reduced in renal failure.

5. the significance of these changes is discussed.