bluuebunny/crossref_metadata_2025 huggingface dataset:
Lactoferrin Turnover in Man
Authors: Bennett R. M. , Kokocinski Theresa
Published: August 2015

1. The turnover of 125I-labelled lactoferrin was measured in ten adults. Simultaneous organ radioactivity counting was performed.

2. Ferrokinetic studies were performed in three adults after the intravenous injection of [59Fe]lactoferrin.

3. Lactoferrin was rapidly eliminated from the plasma with a mean fractional catabolic rate of 5·7/day. Apolactoferrin (one subject) was eliminated at a slower rate (fractional catabolic rate 1·22/day).

4. Of the administered 125I label 99% was recovered in the urine, as free iodine, within the first 24 h. In the 59Fe studies no appreciable activity was found in the urine.

5. Organ radioactivity counting showed that lactoferrin was rapidly taken up by the liver and spleen. In the 125I studies the rapid excretion of free 125I suggested catabolism at these sites. In the 59Fe studies, the radioactivity persisted in the liver and spleen for several weeks and was slowly transferred to the bone marrow before appearing in circulating erythrocytes.

6. From the values of fractional catabolic rate, plasma lactoferrin, neutrophil lactoferrin and plasma volume, a ‘derived neutrophil turnover’ was calculated for each subject. The mean value was 8 × 108 neutrophils/day. This is about 1% the value obtained from the actual measurement of labelled cells. It is postulated that this ‘derived value’ represents only that portion of neutrophil turnover accounted for by intravascular senescence.
The Effect of Pentobarbitone on Plasma and Intracellular Sodium, Potassium and pH in Rabbit Cardiac and Skeletal Muscle
Authors: Hall R. J. C. , Cameron I. R.
Published: August 2015

1. Pentobarbitone anaesthesia, in rabbits, produces (i) hypokalaemia, (ii) increased intracellular potassium and reduced intracellular sodium in cardiac and skeletal muscle.

2. These changes suggest that the hypokalaemia which accompanies anaesthesia results from movement of potassium between the extracellular and intracellular compartments.
Angiotensin II Blockade during Combined Thiazide—β-Adrenoreceptor-Blocker Treatment
Authors: Ibsen H. , Leth A. , McNair A. , Giese J.
Published: August 2015

1. Sixteen patients (11 male, five female), median age 41 years, with essential hypertension insufficiently controlled by hydrochlorothiazide (75 mg/day; diastolic blood pressure ≥ 100 mmHg), were studied.

2. Plasma renin concentration [renin], plasma angiotensin II concentration ([ANG II]), plasma volume and exchangeable sodium (NaE) were determined, and a saralasin infusion (5·4 nmol min−1 kg−1) was carried out while the patients were on thiazide alone and, in 14 cases, 3 months after addition of a β-adrenoreceptor blocker (propranolol, six, metoprolol, six, and atenolol, two patients).

3. On thiazide alone, saralasin caused a significant decrease in mean arterial blood pressure in 12 out of 16 patients. The saralasin response was closely related to pre-saralasin plasma [ANG II] (r = −0·73, P < 0·01). Plasma [renin] and [ANG II] were higher than normal in the group as a whole.

4. After addition of a β-adrenoreceptor blocker systolic and diastolic blood pressure decreased from 164/109 mmHg to 136/94 mmHg. Plasma [renin] and [ANG II] decreased by 40 and 58% respectively. At this point, saralasin caused no significant change in mean arterial pressure. No close correlation was found between plasma [renin] or [ANG II] or saralasin response on thiazide treatment and changes in blood pressure during subsequent thiazide/β-adrenoreceptor-blocker treatment. Plasma volume and NaE did not change significantly.

5. In patients with thiazide-induced stimulation of the renin—angiotensin system, addition of a β-adrenoreceptor blocker leads to suppression of the system and, at the same time, ANG II-dependence of blood pressure disappears. This contributes to the antihypertensive effect of β-adrenoreceptor blockers in this particular situation.
Captopril in Hypertension with Renal Artery Stenosis and in Intractable Hypertension; Acute and Chronic Changes in Circulating Concentrations of Renin, Angiotensins I and II and Aldosterone, and in Body Composition
Authors: Atkinson A. B. , Brown J. J. , Fraser R. , Leckie B. , Lever A. F. , Morton J. J. , Robertson J. I. S.
Published: August 2015

1. The converting-enzyme inhibitor captopril has been given in doses up to 450 mg daily to hypertensive patients with renal artery stenosis and to patients resistant to other therapy.

2. Captopril alone was effective in controlling hypertension in renal artery stenosis, irrespective of whether pretreatment plasma angiotensin II was raised or normal, except in one man with overall renal impairment.

3. In one woman with the hyponatraemic hypertensive syndrome secondary to renal artery thrombosis, captopril restored depleted exchangeable sodium and potassium to normal. In the other cases of renal artery stenosis with normal renal function, exchangeable sodium and total body potassium were not significantly altered, and there were no marked changes in plasma sodium and potassium.

4. The combination of captopril with a diuretic controlled blood pressure long-term in every case of previously resistant hypertension.

5. Within 2 h, captopril induced highly significant falls in arterial pressure, in plasma angiotensin II and aldosterone, with converse increases in plasma active and total renin and blood angiotensin I.

6. The initial fall in plasma angiotensin II was closely related to the concomitant fall in diastolic pressure.

7. The pattern of change in circulating renin, angiotensins I and II and aldosterone was maintained during long-term therapy, whether or not a diuretic was added. There was no tendency for plasma angiotensin II to increase despite sustained elevation of active renin and angiotensin I.
Effect of Baroreceptor Deafferentation on Central Catecholamines in the Rat
Authors: Petty Margaret A. , Chalmers J. P. , Brown M. , Reid J. L.
Published: August 2015

1. Sinoaortic deafferentation in the rat leads to increased blood pressure and heart rate.

2. Early increases in tyrosine hydroxylase activity both in brain stem and hypothalamus suggest that increased noradrenaline synthesis may contribute to the development of neurogenic hypertension.

3. After 4 weeks, phenylethanolamine-N-methyltransferase activity was reduced in the hypothalamus.

4. Noradrenaline- and adrenaline, but not dopamine-containing neurones may participate in regulation of sympathetic efferent activity.
The Kallikrein—Kinin System in Blood Pressure Homeostasis
Authors: Lee T. C. , Kushiro T. , Gassia J.-P. , Girolami J.-P. , Lupu A. N. , Maxwell M. H.
Published: August 2015

1. The acute effects of the kallikrein inhibitor aprotinin (498 ki.u./min), and the kininase II inhibitor SQ 14 225 (250 μg), given intravenously during saralasin-induced angiotensin blockade, were studied in conscious sham-operated rats and rats with benign and malignant two-kidney, one-clip Goldblatt hypertension during dietary sodium restriction.

2. The blood pressure of conscious sham-operated rats increased significantly in response to aprotinin. It remained unchanged after SQ 14 225 in contrast to the significant vasodepressor effect seen when SQ 14 225 was given to the same rats under surgical stress and pentobarbital anaesthesia.

3. Benignly hypertensive rats showed a consistent vasopressor response to aprotinin and a marked vasodepressor response to SQ 14 225. The effects of both inhibitors were markedly and significantly blunted in malignantly hypertensive rats.

4. Our demonstration that two agents with known opposite actions on the kallikrein—kinin system produced predictable and opposite effects on blood pressure may indicate that this system is involved in the homeostatic regulation of blood pressure. It may play an important antihypertensive role in benign two-kidney, one-clip Goldblatt hypertension, a role which might be impaired in malignant hypertension.
Studies on the Mechanism of Mineralocorticoid-Induced Blood Pressure Increase in Man
Authors: Distler A. , Philipp T. , Lüth B. , Wucherer G.
Published: August 2015

1. To gain insight into the mechanism of mineralocorticoid-induced blood pressure rise in man we performed haemodynamic studies in six normotensive volunteer subjects before and during administration of the synthetic steroid 9α-fluorocortisol (0·8 mg daily) for a period of 6 weeks. In a further study, performed in seven subjects, plasma noradrenaline concentration and reactivity to exogenous noradrenaline were determined before and during administration of the mineralocorticoid.

2. Within the first week of steroid administration an increase in mean arterial blood pressure could be demonstrated, which was due to an increase in cardiac output. After the sixth week the elevated blood pressure was the consequence of an increased total peripheral resistance.

3. Plasma noradrenaline concentration decreased and reactivity to exogenous noradrenaline increased during steroid administration.

4. The mechanism underlying the increase in total peripheral resistance during long-term mineralocorticoid administration remains unclear. Increased sympathetic tone does not seem to be a factor since plasma noradrenaline decreased considerably. Pressor response to noradrenaline increased probably due to decreased sympathetic tone.
Lower Body Negative Pressure: A Method to Differentiate Vasodilators in the Intact Rat
Authors: De Metz J. E. , Van Zwieten P. A.
Published: August 2015

1. In rats lower body negative pressure induced venous pooling in a reproducible manner. The response to LBNP in the pentobarbitone-anaesthetized rat appeared not to be influenced by the autonomic nervous system.

2. The hypotensive effect of arterial vasodilators was diminished at 5 mmHg LBNP, compared with effects at 3 mmHg, whereas the hypotensive effect of venous vasodilators was not changed at 5 mmHg LBNP, compared with that at 3 mmHg LBNP.

3. In the pithed rat dihydroergotamine caused venoconstriction. In the phenobarbitone-anaesthetized rat the hypotensive effect of venous vasodilators was decreased significantly by pretreatment with this drug, whereas it did not influence the hypotensive effect of arterial vasodilators.

4. Thus venodilatation by LBNP and venoconstriction by dihydroergotamine provide a method for differentiating arterial and venous sites of action of vasodilators in intact rats.
The Pathogenesis of Propranolol-Withdrawal Syndrome in Essential Hypertension
Authors: Kristensen B. Ø. , Steiness EVA , Weeke J.
Published: August 2015

1. In hypertension, the β-adrenoreceptor-blocker-withdrawal syndrome comprises tachycardia, sweating, tremor and general malaise, symptoms resembling thyrotoxicosis.

2. The effect of abrupt cessation of propranolol on serum concentrations of thyroxine (T4) and tri-iodothyronine (T3) was therefore investigated in five patients with uncomplicated essential hypertension, treated with propranolol in doses from 160 to 480 mg/day.

3. Four of the five patients developed one or more of the above-mentioned symptoms within 2–6 days after withdrawal of propranolol.

4. A mean relative increase in serum free T3 of 51% (range 22–74%) was found in these four patients on the day of onset of symptoms.

5. The increase in free T3 in the five patients correlated positively with total serum propranolol on the last day the drug was given (r = 0·91, 2P = 0·03).

6. As an increase in T3 was found only in patients suffering the withdrawal syndrome, and was maximal the day the symptoms appeared, despite a variation in time of onset from 2 to 6 days, it is suggested that the β-adrenoreceptor-blocker-withdrawal syndrome, at least partially, is caused by a rebound increased production of T3, induced by the well-known inhibition of the monodeiodination of T4 to T3 during β-adrenoreceptor blockade.

7. This assumption may explain the clinical symptoms and the reported transient increased β-adrenoreceptor sensitivity with unchanged serum concentrations of catecholamines.
Vasodepressor Property of the Converting Enzyme Inhibitor Captopril (SQ 14 225): The Role of Factors other than Renin-Angiotensin Blockade in the Rat
Authors: Marks E. S. , Bing R. F. , Thurston H. , Swales J. D.
Published: August 2015

1. The peptide converting enzyme inhibitor captopril was given (1·25 mg/kg intravenously) to normal and nephrectomized rats and rats with renovascular and deoxycorticosterone hypertension.

2. Captopril lowered blood pressure to a small extent in normal and nephrectomized rats. Bradykinin infusion in nephrectomized animals, however, potentiated the vasodepressor action of captopril.

3. Captopril produced a major blood pressure fall in the early stages of Goldblatt two-kidney one-clip hypertension: even when hypertension had been present for more than 4 months, a substantial vasodepressor action was seen. Rats with deoxycorticosterone-induced hypertension also showed a significant blood pressure fall.

4. Captopril was given to salt-loaded and salt-depleted rats in which the renin-angiotensin system had been blocked by infusion of the competitive angiotensin II antagonist saralasin. Captopril still lowered blood pressure in the salt-depleted group.

5. Captopril lowers blood pressure in situations where the renin-angiotensin system is not responsible for blood pressure maintenance. Further, the fall in blood pressure produced in Goldblatt two-kidney one-clip hypertension is greater than would be predicted on the basis of renin-angiotensin blockade. It is likely therefore that captopril lowers blood pressure by an action additional to angiotensin blockade. Bradykinin potentiation is one possible mechanism by which this may take place.
Peripheral Resistance to the Cellular Action of Insulin in Obese Diabetic Subjects In Vivo
Authors: Reckless J. P. D. , Galton D. J.
Published: August 2015

1. The concentrations of adenosine 3′:5′-cyclic monophosphate (cyclic AMP) in human adipose tissue were studied after intravenous insulin administration (0·3 unit/kg body weight) in obese diabetic and obese non-diabetic subjects.

2. The declines in plasma glucose, glycerol and free fatty acids in the two groups after insulin were similar if allowances were made for the fasting hyperglycaemia in the diabetic subjects.

3. Insulin in vivo lowered the concentrations of cyclic AMP in adipose tissue from non-diabetic subjects.

4. Insulin administration in vivo did not alter the tissue concentrations of cyclic AMP in adipose tissue of obese diabetic subjects. This lack of effect of insulin provides evidence for tissue resistance in vivo to the action of insulin in diabetes mellitus.
Growth Hormone Secretion in Hypertensive Patients: Evidence for a Derangement in Central Adrenergic Function
Authors: Barbieri C. , Ferrari C. , Caldara R. , Curtarelli G.
Published: August 2015

1. In an attempt to test the hypothesis of a derangement in central catecholaminergic function in hypertensive patients, the serum growth hormone and prolactin responses to the α-adrenergic agonist clonidine (0·15 mg infused intravenously) and to l-dopa administration (500 mg orally) were evaluated in 15 hypertensive and 15 normotensive subjects matched for sex, age and body weight.

2. Whereas l-dopa elicited a growth hormone response of similar magnitude in both groups, clonidine infusion induced a significant increase in serum growth hormone in normotensive, but not in hypertensive, subjects.

3. Prolactin levels were equally suppressed by l-dopa and did not change after clonidine in either group.

4. The present study adds neuroendocrine evidence to the concept of a derangement in central α-adrenergic function in human hypertension.
Correlation of Plasma Phenformin Concentration with Metabolic Effects in Normal Subjects
Authors: Nattrass M. , Sizer Karen , Alberti K. G. M. M.
Published: August 2015

1. Circulating concentrations of intermediary metabolites have been measured after administration of 50 mg of phenformin to normal subjects.

2. Phenformin caused a significant increase in blood lactate, alanine and the lactate/pyruvate ratio but did not affect blood glucose or serum insulin concentrations.

3. There was a significant correlation between the increase in blood lactate concentration after phenformin and the plasma concentration of the drug.
Characterization of the Storage Material of Peripheral Lymphocytes in Aspartylglycosaminuria
Authors: Maury P. , Palo J.
Published: August 2015

1. Aspartylglycosaminuria is a neurovisceral storage disease characterized by reduced or absent activity of the lysosomal enzyme N-aspartyl-β-glucosaminidase. Although vacuolization of peripheral lymphocytes is a well-documented feature of aspartylglucosaminuria, the chemical composition of the lymphocyte storage material is not known. In this paper we describe the results of glycopeptide analyses of peripheral lymphocytes isolated from the blood of a 29-year-old female patient with aspartylglycosaminuria and from a control subject.

2. By use of a highly specific and sensitive gaschromatographic-mass-spectrometric technique, 4-N-2-acetamido-2-deoxy-β-d-glucopyranosyl-l-as-paragine (N-acetylglucosaminylasparagine) was found to accumulate in the patient's lymphocytes, but not in those of the control subject.

3. The amount of this compound stored in the diseased lymphocytes was found to be approximately 2·3 nmol/100 μg of soluble protein.

4. We suggest that this compound is the main storage substance in the peripheral lymphocytes in aspartylglucosaminuria and that it is probably responsible for the cytoplasmic vacuolization of these cells.
Selective and Non-Selective β-Adrenoreceptor Blockade in the Human Forearm
Authors: Hartling O. J. , Noer I. , Svendsen T. L. , Clausen J. P. , Trap-Jensen J.
Published: August 2015

1. The immediate effects of selective (β1) and non-selective (β1+2) β-adrenoreceptor blockade on local blood flow and substrate exchange were studied in young male subjects at rest and during dynamic forearm exercise. After a control period of rest, exercise and recovery, atenolol (β1), propranolol (β1+2) or placebo was infused into the right brachial artery during a second period of rest, exercise and recovery.

2. Neither atenolol nor propranolol influenced forearm blood flow during exercise. Atenolol and propranolol reduced the increase in lactate release from the forearm during exercise by 39 and 34% respectively. Neither agent influenced oxygen and glucose uptake. Propranolol increased forearm uptake of free fatty acids during exercise by 135%. A concomitant fall in forearm respiratory quotient indicated an increased utilization of free fatty acids. Atenolol did not affect free fatty acids uptake or respiratory quotient.

3. Blockade of vascular β2-receptors does not seem to be important for the blood flow regulation during muscular exercise. Both selective and non-selective β-adrenoreceptor blockade reduce the lactate release from exercising skeletal muscle, but appear to have different effects on fat metabolism.
Preliminary Evidence for the Conversion of Dog Renin into a Higher—Molecular—Weight Form by Cold Storage
Authors: Kawamura Minoru , Ikemoto Fumihiko , Yamamoto Kenjiro
Published: August 2015

1. A soluble fraction of renal cortical homogenate (cytosol) and renin extracted from isolated renin granules of the dog kidney were kept at 0°C.

2. Although the molecular weight of the renin in the cytosol on day 1 was estimated to be about 40 000 by gel filtration, the renin was completely converted into a higher—molecular—weight form (60 000) by day 7. The renin in the granules kept its molecular size of 40 000 during cold storage.

3. This type of molecular—weight conversion could be performed without protease inhibitors.

4. Dithiothreitol neither inhibited the conversion into the higher—molecular—weight form of renin during cold storage nor led to a reduction in the molecular weight of renin, although the oxidation of thiol groups has been proposed as the mechanism for the molecular—weight conversion of renin.

5. Keeping a mixture of renin from the granules and crude renin—binding substance at 0°C for 7 days resulted in the conversion of the renin into the higher—molecular—weight form, indicating that the renin—binding substance we have previously described is required for the conversion during cold storage.

6. Acidification caused the higher—molecular—weight form of renin formed in the cytosol to change to the lower—molecular—weight form, with a concomitant increase in activity of about 50%.
Determination of the Pool Size and Synthesis Rate of Bile Acids by Measurements in Blood of Patients with Liver Disease
Authors: Engelking L. R. , Barnes S. , Hirschowitz B. I. , Dasher C. A. , Spenney J. G. , Naftel D.
Published: August 2015

1. A simplified technique for the measurement of bile-acid pool size and synthesis rate has been developed in patients with liver disease. Isotope dilution studies in blood and bile were performed after intravenous injection of [24–14C]cholic acid with radioimmunoassay for the measurement of the bile-acid concentration. The interpolated pool sizes and synthesis rates, determined from results from both blood and bile, were not significantly different The concentration of bile acids in the blood of healthy controls was not sufficiently elevated to permit application of this technique.

2. Three out of six patients with cirrhosis had a markedly reduced pool size compared with that of controls, whereas those with cholestasis had an unchanged pool size. The daily synthesis rate was reduced in both groups. Liver disease caused a redistribution
Role of Antidiuretic Hormone in Impaired Urinary Dilution Associated with Chronic Bile-Duct Ligation
Authors: Better O. S. , Aisenbrey G. A. , Berl T. , Anderson R. J. , Handelman W. A. , Linas S. L. , Guggenheim S. J. , Schrier R. W.
Published: August 2015

1. The effect of chronic bile-duct ligation on systemic and renal haemodynamics and on the capacity to dilute the urine was studied in conscious rats. Sham-operated rats served as controls.

2. In the rats with bile-duct ligation, the maximal urinary diluting capacity was impaired, despite an expanded plasma volume, a normal mean arterial pressure and cardiac output, and normal intrarenal determinants of water excretion including distal delivery of fluid and function of the diluting segment.

3. In contrast, maximal urinary dilution capacity was intact in rats with congenital central diabetes insipidus and chronic bile-duct ligation.

4. It is concluded that the defect in urinary dilution in rats with chronic bile-duct ligation is dependent on antidiuretic hormone.
Effect of Aging on Energy-Rich Phosphagens in Human Skeletal Muscles
Authors: Möller P. , Bergström J. , Fürst P. , Hellström K.
Published: August 2015

1. Biopsy specimens of muscle obtained after an overnight rest from 14 men and eight women, apparently healthy subjects (age range 52–79 years), were analysed for pyruvate, lactate and energy-rich phosphagens.

2. Values for metabolites showed no sex differences. Compared with previous findings in men and women about 40 years younger, the intramuscular concentrations of both total adenine nucleotides and phosphocreatine were approximately 5% lower in the elderly. Creatine was correspondingly increased, but total creatine was unchanged, as were the ATP and the ATP/ADP ratio.

3. It was concluded that energy-rich compounds showed significant but small age-related variations.
The Relation between Bone Loss and Calcium Balance in Women
Authors: Horsman A. , Marshall D. H. , Nordin B. E. C. , Crilly R. G. , Simpson M.
Published: August 2015

1. We have examined the relation between the rate of cortical bone loss and other measured variables in 108 women, untreated and on various therapies, observed for nearly 300 patient years. The majority of the subjects were post-menopausal women with various degrees of simple osteoporosis, but a few cases of hyperparathyroidism and other calcium disorders were included.

2. Calcium balance, bone resorption rate, urinary hydroxyproline and plasma alkaline phosphatase were shown to be related to the rate of bone loss; patients with the more negative balance or the higher values of the other variables had significantly higher rates of loss. The rate of bone loss was independent of the rate of bone formation.
The Influence of Indomethacin on Renal Haemodynamics in Sickle Cell Anaemia
Authors: De Jong P. E. , Den Berg L. T. W. De Jong-Van , Sewrajsingh G. S. , Schouten H. , Donker A. J. M. , Van Eps L. W. Statius
Published: August 2015

1. Glomerular filtration rate and effective renal blood-flow were normal in a series of patients with sickle cell anaemia. Fractional creatinine excretion and fractional urea excretion were increased.

2. During indomethacin administration there were significant falls in glomerular filtration rate, effective renal blood-flow, creatinine clearance and urea clearance in the patients with sickle cell anaemia; fractional urea excretion also fell markedly. In control subjects none of these variables changed after indomethacin.

3. Serum concentration of urea rose markedly during indomethacin administration in sickle cell anaemia, owing to both the decrease in glomerular filtration rate and the increase in fractional urea reabsorption.

4. We conclude that prostaglandins have an important role in maintaining a normal glomerular filtration rate and effective renal blood-flow in sickle cell anaemia. The abnormal urea handling in patients with this disease remains to be elucidated.
The Influence of Carbohydrate Gelling Agents on Rat Intestinal Transport of Monosaccharides and Neutral Amino Acids in Vitro
Authors: Elsenhans B. , Süfke U. , Blume R. , Caspary W. F.
Published: August 2015

1. In the present investigation with rings of everted rat small intestine, carbohydrate gelling agents (plant polysaccharides) such as guaran, pectin, tragacanth, carubin and carrageenan were employed to study their direct effect on intestinal absorption of α-methyl-d-glucoside, d-galactose, l-leucine and l-phenylalanine.

2. Inhibition was found to correlate with the viscosity of the incubation medium, a function only of the polysaccharide concentration, and was independent of other properties of the carbohydrate gelling agents.

3. Reversal of this inhibition was achieved either by washing the tissue free of polysaccharide or by raising tissue agitation.

4. Uptake kinetics in polysaccharide-containing solutions revealed a marked increase of the apparent Michaelis constant although the maximal transport capacity remained essentially unaltered.

5. Since there was no binding of the substrate by the polysaccharides under experimental conditions as judged by a membrane filtration technique, it is concluded that carbohydrate gelling agents may impair intestinal absorption by means of an increased unstirred layer resistance.
The Effect of 3-Methylhistidine in Food on its Urinary Excretion in Man
Authors: Elia M. , Carter A. , Bacon S. , Smith R.
Published: August 2015

1. To establish whether 3-methylhistidine in food is quantitatively excreted in the urine, five normal adults on a vegetarian diet were given known amounts of 3-methylhistidine in meat or fish. The mean cumulative 5-day increment in 3-methylhistidine excretion in non-hydrolysed urine accounted for an average of 90% of the 3-methylhistidine given during the first 3 days of this period.

2. To define the variation in urinary 3-methylhistidine on a constant mixed intake, the daily 3-methylhistidine excretion was measured for 6 days in four patients on a metabolic ‘balance’ diet. The mean daily variation was less than 10%.

3. The results show that under the conditions of this study the increase in urinary 3-methylhistidine above basal levels can be quantitatively accounted for by the 3-methylhistidine content of additional food; in subjects on a constant diet it should be possible to detect relatively small changes in 3-methylhistidine excretion.
Angiotensin II and Not Sodium Status is the Major Determinant of the Agonistic/Antagonistic Balance of Saralasin's Actions
Authors: Fagard R. , Amery A. , Lijnen P.
Published: August 2015

1. To study which factors determine the balance between the antagonistic and agonistic effects of the angiotensin II analogue [Sar1,Ala8]-angiotensin II (saralasin) in man, saralasin was infused in subjects on a ‘normal’ sodium intake (group 1) during sodium restriction with appropriately elevated plasma angiotensin II levels (group 2) and in sodium-restricted subjects in whom plasma angiotensin II was suppressed by converting enzyme inhibition with captopril (group 3).

2. The action of saralasin was agonistic in group 3, antagonistic in group 2 and variable in group 1.

3. For groups 1 and 2 together the saralasin-induced changes of arterial pressure, of plasma aldosterone and of plasma renin were significantly related to control plasma angiotensin II but also to the 24 h urinary sodium excretion. When group 3 was included the changes remained significantly related to plasma angiotensin II but not to the urinary sodium excretion.

4. The results indicate that angiotensin II and not sodium status determines the agonistic/antagonistic balance of saralasin's actions.
The Renin-Angiotensin-Aldosterone System in the Maintenance of Blood Pressure, Aldosterone Secretion and Sodium Balance in Normotensive Subjects
Authors: MacGregor G. A. , Markandu N. D. , Roulston J. E. , Jones J. C. , Morton J. J.
Published: August 2015

1. Captopril given for 5 days caused a fall in blood pressure in normotensive subjects. The percentage fall in mean supine pressure was greatest on a low sodium diet (10 mmol/day), 19.6%, least on a high sodium diet (350 mmol/day), 11%, and in between on a normal sodium diet (120 mmol/day), 16.5%.

2. Captopril caused a marked fall in plasma aldosterone in normal subjects on all three sodium intakes.

3. Captopril caused an increase in sodium excretion on the normal (120 mmol/day) and low (10 mmol/day) sodium diet but not the high sodium diet.

4. These results suggest that the renin-angiotensin-aldosterone system is a normal mechanism for maintaining blood pressure and aldosterone secretion in normotensive man. The system may also be involved in the maintenance of sodium balance.

5. These results may lead to a better understanding of the role of the renin-angiotensin-aldosterone system in the maintenance or causation of high blood pressure in essential hypertension.
Intrarenal Conversion of Prostaglandin F2α Into Prostaglandin E2 and Renin Release in the Isolated Perfused Rat Kidney
Authors: Schwertschlag U. , Seyberth H. W. , Müller H. , Grunewald R. , Erlenmaier T. , Rohs H. G. , Hackenthal E.
Published: August 2015

1. Isolated rat kidneys were perfused with a modified Krebs-Henseleit medium at constant pressure.

2. When prostaglandin F2α (PGF2α) was infused into these kidneys at 0.1 μmol/l (final concentration) PGF2α-derived prostaglandin E2 (PGE2) could be identified by high-performance liquid chromatography and combined gas chromatography-mass spectrometry.

3. The extent of this conversion of PGF2α into PGE2 during passage through the kidney is dependent on the salt history of the rats from which the kidneys were taken for perfusion: kidneys from rats kept on normal diet converted 10%, those from rats on a low sodium diet 5% and those from rats kept on a high sodium diet 11%.

4. These differences in conversion can account for the different increases in renin release after PGF2α infusion in these groups.
Diminished Urinary Prostacyclin Metabolite in Essential Hypertension
Authors: Grose J. H. , Lebel M. , Gbeassor F. M.
Published: August 2015

1. Urinary excretion rate of 6-keto-prostaglandin F1α (6-keto-PGF1α), a stable non-enzymatic transformation product of prostacyclin (PGI2), was measured in 13 patients with sustained essential hypertension and in nine normotensive control subjects by a specific radioimmunoassay.

2. Patients with essential hypertension had significantly lower 6-keto-PGF1α excretion rates irrespective of their sex, but in both groups urinary 6-keto-PGF1α was lower in females.

3. Sodium excretion was significantly correlated with urinary 6-keto-PGF1α only in hypertensive subjects. There was also a positive correlation between 6-keto-PGF1α and urine volume in control subjects and in hypertensive patients.

4. If diminished urinary 6-keto-PGF1α reflects suppressed endogenous PGI2 production, a deficiency in this important vasodepressor substance in essential hypertension may contribute to the pathogenesis of this disease.
Enhanced Sympathetic Activity Caused by Salt Loading in Spontaneously Hypertensive Rats
Authors: Dietz R. , Schoumig A. , Rascher W. , Strasser R. , Kubler W.
Published: August 2015

1. Salt loading accelerates and increases the rise in blood pressure (spSH) in stroke-prone spontaneously hypertensive rats, but not in Wistar-Kyoto (WK) rats.

2. In both strains a slight increase in plasma volume was obtained during salt loading.

3. Salt loading caused a distinct increase in plasma noradrenaline concentration in spSH rats, but a slight decrease in WK rats. Plasma adrenaline and dopamine concentrations remained unaffected.

4. Exposure to cold resulted in a more marked stimulation of sympathoadrenal and sympathoneuronal activity in salt-loaded spSH rats than in spSH rats on a normal sodium diet.

5. It is concluded that salt loading results in a further increase of the already elevated sympathetic activity in spSH rats.
Stimulation of Peripheral Dopamine Receptors in Rats: A Mechanism for Novel Antihypertensive Agents
Authors: Lefegvre-Borg Francloise , Cavero Icilio
Published: August 2015

1. The aim of this investigation was to provide support for the hypothesis that stimulation of peripheral dopamine receptors reduces sympathetic vasomotor tone and thus may be a mechanism for novel antihypertensive agents.

2. NN-Di-n-propyldopamine (DPDA: 0.03-0.1 mg min−1 kg−1 intra-arterially) produced sustained decreases in blood pressure measured from the cannulated tail artery in conscious spontaneously hypertensive rats.

3. This antihypertensive action of DPDA was antagonized by sulpiride but not by atropine, promethazine, propranolol or indomethacin.

4. DPDA failed to lower blood pressure in spontaneously hypertensive rats in which peripheral stores of catecholamines had been previously depleted with syrosingopine.

5. In the pithed atropine-pretreated spontaneously hypertensive rats in which the low blood pressure was elevated by electrical stimulation of the spinal cord, DPDA produced hypotensive effects which were antagonized by sulpiride. However, DPDA, in contrast to phentolamine, did not modify the blood pressure raised by an infusion of adrenaline.

6. In conclusion, the blood pressure-lowering action of DPDA is due to stimulation of dopamine receptors which decreases noradrenaline release and consequently sympathetic vasomotor tone. These receptors may be located on sympathetic ganglia or sympathetic endings innervating resistance vessels.
Plasma Catecholamine Levels and Vascular Response in Deoxycorticosterone Acetate Hypertension of Rats
Authors: Rascher W. , Dietz R. , Schomig A. , Weber J. , Gross F.
Published: August 2015

1. In rats with deoxycorticosterone acetate (DOCA) hypertension basal plasma concentrations of noradrenaline and adrenaline correspond to those of sham-treated controls.

2. In DOCA-treated rats frusemide caused a more pronounced increase in plasma noradrenaline than in control rats. This difference was not observed for adrenaline.

3. In the isolated perfused hind-limb preparation the sensitivity to noradrenaline was already enhanced before blood pressure was elevated.

4. These results suggest that the adrenergic vascular tone is increased in DOCA hypertension in rats.
Hyperplasia of Rat Arteries Smooth Muscle Cells Associated with Development and Reversal of Renal Hypertension
Authors: Rorive G. L. , Carlier P. J. , Foidart J. M.
Published: August 2015

1. Renal hypertension produces a marked and rapidly detectable hypertrophy of the rat aorta, due to smooth muscle cell hyperplasia and connective tissue deposition.

2. As we described previously for collagen synthesis, cell hyperplasia is a very early event which reaches a maximum at a time when the blood pressure is far from its highest level, and thereafter progressively decreases.

3. Reserpine prevents the vascular wall changes on the arterial as well as the venous side of the circulation. On the other hand, captopril although effective in preventing the blood pressure rise does not suppress the hyperplastic response.

4. The arterial hypertensive disease appears to be reversible, when renal ischaemia is corrected. The smooth muscle cell hyperplasia is, however, only partly and slowly reversible.

5. These data suggest that blood pressure is not the only determinant of the vascular wall response, and that the effect of a drug on the blood pressure does not necessarily predict the vascular wall response.
Effect of Morphine on Limb Capacitance and Resistance Vessels
Authors: Cohen R. A. , Coffman J. D.
Published: August 2015

1. The actions of 15 mg of intravenous morphine on hand and forearm capacitance and resistance vessels were studied with venous occlusion plethysmography.

2. In contrast to a 5% increase in forearm venous volume, intravenous morphine caused a 26% decrease in hand venous volume. This hand venoconstriction was confirmed by finding an increase in hand venous tone. The effects of morphine on hand veins were attenuated by intra-arterial phentolamine and blocked by intravenous naloxone.

3. Whereas morphine had no significant effect on forearm resistance vessels, it caused a 70% reduction in hand vascular resistance.

4. Intra-arterial morphine had no local action on hand capacitance or resistance vessels.

5. Though the contrasting actions of morphine on hand and forearm capacitance vessels resulted in no important change in limb venous capacitance, the large reduction of cutaneous vascular resistance may contribute to haemodynamic benefit in patients with pulmonary oedema.
Direct Measurement of Hepatic Extraction of Bile Acids in Subjects with and without Liver Disease
Authors: Gilmore I. T. , Thompson R. P. H.
Published: August 2015

1. The hepatic extraction ratio of 14C-labelled bile acids has been measured directly by hepatic vein catheterization in five patients without liver disease (glycocholic acid, three; cholic acid, two) and in 16 patients with histologically confirmed liver disease (glycocholic acid, seven; cholic acid, nine).

2. After intravenous administration of [14C]-glycocholic acid by bolus injection (two control subjects) or constant infusion (one control subject), directly measured hepatic extraction ratio was 0.91, 0.84 and 0.88, greater than that for indocyanine green. The extraction ratio of [14C]cholic acid in two subjects was 0.72 and 0.70, confirming a lower extraction of the unconjugated bile acid.

3. The hepatic extraction ratio of both bile acids was reduced in patients with chronic liver disease (range 0.07–0.69), although the extraction ratio of glycocholic acid remained normal in one patient with viral hepatitis.

4. Estimates of liver flow calculated from the extraction of [14C]glycocholic acid, but not cholic acid, correlated with those calculated from indocyanine green kinetics, although numbers were small.

5. Measurement of the hepatic extraction of individual bile acids, not previously reported in man, allows a more accurate description of the enterohepatic circulation.
The Turnover of Plasma Glucose and Free Fatty Acids in Vivo after Portacaval Anastomosis and Chronic Underfeeding in the Rat
Authors: Sarna G. S. , Cunningham V. J. , Tucker Sheron , Cremer Jill E.
Published: August 2015

1. The metabolic status of rats after end-to-side portacaval anastomosis and the extent to which this differs from sham-operated animals, both fed and pair-fed, was investigated.

2. The body weights of sham-operated pair-fed rats consistently matched the weights of animals with a portacaval anastomosis at different times after the operation, whereas liver weights were significantly reduced in anastomosed animals as compared with the other groups.

3. Plasma glucose, insulin and the irreversible disposal rates for plasma glucose (determined by single intravenous injection of [6-3H]glucose) were similarly and significantly reduced for animals with a portacaval anastomosis and sham-operated pair-fed animals as compared with sham-operated fed control rats.

4. In contrast, plasma free fatty acid levels were significantly higher in animals with a portacaval anastomosis as compared with both sham-operated fed control and sham-operated pair-fed groups of animals. Turnover of plasma free fatty acids was measured in vivo by single intravenous injection of [1-14C]palmitic acid. The raised levels of plasma free fatty acids in animals with a portacaval anastomosis were principally due to reduced clearance and not to an increase in lipolysis.

5. Plasma β-hydroxybutyrate levels were similar in sham-operated fed control rats and animals with a portacaval anastomosis. Pair-fed values were three to four times greater than sham-operated fed control values and after portacaval anastomosis and increased further after a period of 24 h fasting. Values obtained for anastomosed animals increased only marginally after 24 h fasting and were significantly lower than pair-fed-animal values.

6. The rat with an end-to-side portacaval anastomosis may be characterized to be in a metabolic state equivalent to a chronically underfed animal in terms of reduced glucose turnover and plasma insulin concentrations but differs in respect to plasma free fatty acid turnover and plasma β-hydroxybutyrate concentrations.
A Comparison of the Effects of Intravenous Infusion of Individual Branched-Chain Amino Acids on Blood Amino Acid Levels in Man
Authors: Eriksson S. , Hagenfeldt L. , Wahren J.
Published: August 2015

1., Intravenous infusions of l-valine (600 μmol/min), l-isoleucine (150 μmol/min), l-leucine (300 μmol/min) and a mixture of the three branched-chain amino acids (70% l-leucine, 20% l-valine, 10% l-isoleucine; 270 μmol/min) were given to four groups of healthy volunteer subjects. Whole-blood concentrations of amino acids and glucose and serum insulin were measured before and during the infusions.

2. Valine and isoleucine infusions resulted in twelve- and six-fold increases in the respective amino acid. During valine infusion, tyrosine was the only amino acid for which a decrease in concentration was seen (25%, P < 0.05). With isoleucine administration, no significant changes were found. In contrast, leucine infusion (during which the leucine concentration rose about sixfold) was accompanied by significant decreases in tyrosine (35%), phenylalanine (35%), methionine (50%), valine (40%) and isoleucine (55%). The arterial glucose concentration fell slightly (5%) and the insulin concentration increased 20% during leucine infusion.

3. Infusion of the mixture of the three branched-chain amino acids resulted in marked decreases in tyrosine (50%), phenylalanine (50%) and methionine (35%). The decreased amino acid levels remained low for 2 h after the end of the infusion.

4. The present findings demonstrate that intravenous infusion of leucine (not infusion of valine or isoleucine) results in marked reductions in the concentrations of the aromatic amino acids and methionine. Infusion of a mixture of the three branched-chain amino acids gives results similar to those obtained with leucine infusion alone. Thus a mixed branched-chain amino acid solution with leucine as its main constituent seems to be the best alternative in the treatment of patients with hepatic cirrhosis and encephalopathy.
Passive Permeability in Experimental Intestinal Damage in Rats
Authors: Cobden I. , Rothwell Jill , Axon A. T. R.
Published: August 2015

1. Experiments were performed to study the absorption of two simultaneously administered polar probes of different molecular size from closed intestinal loops in rats subjected to various mucosal structural lesions.

2. Absorption of mannitol (molecular radius approximately 0.40 nm) was significantly decreased in rats with villous atrophy and crypt hypoplasia induced by the cytostatic agent methotrexate. The absorption of lactulose (radius approximately 0.54 nm) was also decreased, in contrast to the increased absorption which was found in an earlier study when villous atrophy with crypt hyperplasia was induced by infection by a nematode. The effect of local damage to villous tips, produced by the intraluminal presence of a detergent, was to increase significantly the absorption of lactulose.

3. In conjunction with the findings of earlier studies, these results support the hypothesis that there are at least two routes for the permeation of polar molecules. Small molecules such as mannitol probably pass through numerous cellular pores with a maximum radius lying between 0.40 and 0.54 nm and absorption is closely related to mucosal surface area. Larger molecules such as lactulose are probably restricted to less numerous extracellular pathways and absorption may be related to cell shedding or other areas of mucosal damage.
Age-Dependence of Noradrenaline Kinetics in Normal Subjects
Authors: Esler M. , Skews H. , Leonard P. , Jackman G. , Bobik A. , Korner P.
Published: August 2015

1. The influence of age on the rate of spillover of noradrenaline into plasma, clearance of noradrenaline from plasma, and plasma noradrenaline concentration at rest was studied in 34 healthy subjects aged 20–69 years.

2. The plasma concentration of noradrenaline was dependent on age, values being higher in older subjects.

3. This age-dependence of plasma noradrenaline concentration was due principally to a reduced clearance of noradrenaline from the circulation in older subjects.

4. The rate of spillover of noradrenaline into plasma was little influenced by age. The higher plasma noradrenaline values found in older subjects do not seem to be due to an increase in sympathetic nervous system tone with aging.
Immunological Responses to Training in Conditioned Runners
Authors: Hanson P. G. , Flaherty D. K.
Published: August 2015

1. We measured the concentrations of leucocyte subpopulations, immunoglobulins and complement in six well-conditioned runners before and after a typical 8-mile (12.8 km) training run at 70–75% of V̇o2 max.

2. Before running all components were within the normal range. Exercise failed to produce a significant rise in neutrophils. There was also no change in immunoglobulins or complement concentrations immediately or 24 h after exercise. Lymphocyte subpopulations were also unchanged except for a progressive rise in antibody-dependent cytotoxic effector cells (K-lymphocytes).

3. These results suggest chronic exercise training has no apparent adverse effect on circulating cellular or humoral immune components in healthy subjects. An increase in K-lymphocytes may provide added host defence capacity during periods of stress, although the mechanism of increase is unexplained.