bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in Cardiac Output during the Development of Renal Hypertension in Sodium-Depleted Dogs
Authors: Davis James O. , Stephens Gregory A. , Freeman Ronald H. , Deforrest Jack M.
Published: August 2015

1. Chronic renovascular hypertension developed in uninephrectomized, sodium-depleted dogs in association with a decrease in cardiac output.

2. With sodium and volume repletion of these animals, cardiac output returned to normal but the high level of arterial pressure was unchanged; consequently, the peripheral arterioles dilated.

3. These observations provide evidence against the theory of whole-body autoregulation.
Effects of Enkephalins on Arterial Blood Pressure are Reduced by Propranolol
Authors: Simon W. , Schaz K. , Ganten U. , Stock G. , Schlör K. H. , Ganten D.
Published: August 2015

1. The cardiovascular effects of enkephalins have been tested in normotensive Wistar—Kyoto rats. Methionine—enkephalin and leucine—enkephalin increased blood pressure and heart rate after infusion into the brain ventricles.

2. After intravenous injection, blood pressure was increased by methionine—enkephalin and leucine—enkephalin, but heart rate was increased by methionine—enkephalin only.

3. Propranolol treatment reduced the increases in blood pressure following intraventricular methionine—enkephalin and leucine—enkephalin, while only the methionine—enkephalin-induced increases in heart rate were reduced by propranolol.

4. Heart rate and blood pressure responses after intravenous administration of methionine— enkephalins and leucine—enkephalin were not affected by propranolol.

5. Since opioid peptides occur in the blood and in regions of the brain involved in blood pressure regulation, the demonstrated cardiovascular effects to intraventricular and intravenous enkephalins support a role of these peptides in central and peripheral mechanisms of blood pressure control.
The Interaction between Prazosin and Clonidine
Authors: Van Zwieten P. A. , Lam E. , Timmermans P. B. M. W. M.
Published: August 2015

1. The interaction between prazosin and clonidine was studied in anaesthetized rats, pithed rats and in anaesthetized cats.

2. Prazosin diminished the clonidine-induced hypotensive effect in anaesthetized rats, probably via an antagonism at the level of central α-adrenoreceptors.

3. In pithed rats, stimulation of the Nervi accelerantes caused tachycardia, which was diminished considerably by clonidine. The antagonism by clonidine was partly reversed by prazosin, suggesting that prazosin possesses a certain degree of presynaptic activity apart from its predominant effect at the postsynaptic α-receptor. Piperoxan was more active than prazosin.

4. The central hypotensive effect of clonidine, injected into the left vertebral artery of cats was significantly reduced by prazosin, administered before clonidine via the same route. Intravenously injected prazosin did not diminish the central hypotensive effect of clonidine. The antagonism is, therefore, caused by a central mechanism.

5. The combined application of clonidine and prazosin in antihypertensive treatment is probably not only irrational but ought to be discouraged in view of the interaction between the drugs, which leads to a reduced antihypertensive potency of clonidine.
Raised Serum Lipid Concentrations during Diuretic Treatment of Hypertension: A Study of Predictive Indexes
Authors: Ames R. P. , Hill P.
Published: August 2015

1. The serum concentrations of cholesterol and triglycerides were measured before and during the treatment of hypertension. Thirty-six patients were treated with hydrochlorothiazide and 29 with spironolactone.

2. Serum cholesterol increased from 214 to 227 mg/100 ml (P < 0·005) and triglyceride did not change during treatment with hydrochlorothiazide. Serum triglyceride increased from 112 to 133 mg/100 ml (P < 0·05) and cholesterol did not change during treatment with spironolactone.

3. Serum lipid responses to diuretics varied among patients. To identify patients susceptible to larger increases, subgroup analysis was carried out. Patients who were younger and had lower pretreatment serum cholesterol and systolic blood pressure had larger increments in cholesterol during treatment. In these subgroups coronary risk status did not improve during therapy.

4. The incidence of myocardial infarction may not be reduced so long as diuretics serve as first-line drugs in the treatment of mild hypertension.
Renin–Angiotensin System in Mild Essential Hypertension. the Functional Significance of Angiotensin II in Untreated and Thiazide-Treated Hypertensive Patients
Authors: Ibsen H. , Leth A. , Hollnagel H. , Kappelgaard A. M. , Nielsen M. Damkjaer , Giese J.
Published: August 2015

1. Twenty-five patients with mild essential hypertension, identified during a survey of a population born in 1936, were investigated.

2. Basal and post-frusemide values for plasma renin concentration and plasma angiotensin II concentration did not differ markedly from reference values in 25 40-year-old control subjects. In the untreated, sodium replete state saralasin infusion (5·4 nmol min−1 kg−1) produced an increase in mean arterial pressure in the patient group as a whole.

3. Twenty-one patients were treated with hydrochlorothiazide, mean dose 75 mg/day for 3 months. Pre-treatment, frusemide-stimulated plasma renin concentration and plasma angiotensin II, and values during thiazide treatment were higher in ‘non-responders’ (n = 10) to hydrochlorothiazide treatment than in ‘thiazide-responders’ (n = 11). During thiazide therapy, angiotensin II blockade induced a clear-cut decrease in mean arterial pressure in all ‘thiazide-nonresponders’ whereas only four out of 11 ‘thiazide-responders’ showed a borderline decline in mean arterial pressure.

4. The functional significance of the renin—angiotensin system in mild essential hypertension emerges only after thiazide treatment. Thiazide-induced stimulation of the renin—angiotensin system counter-balanced the hypotensive effect of thiazide in some 40% of the treated patients. Thus the responsiveness of the renin—angiotensin system determined the blood pressure response to thiazide treatment.
Relationship of Blood Pressure to Sodium Excretion in a Population Survey
Authors: Simpson F. O. , Waal-Manning H. J. , Bolli P. , Phelan E. L. , Spears G. F. S.
Published: August 2015

1. Blood pressure, height, weight and 24 h urinary output of sodium, potassium and creatinine were measured in over 500 adults of each sex during a health survey of the population of a small town.

2. Both systolic and diastolic pressure were significantly related to Quetelet's index (weight/height2) and heart rate.

3. There was no significant relationship between blood pressure and output of sodium or potassium, sodium/potassium ratio or sodium/creatinine ratio.
Blood Pressure Circadian Rhythm in Essential Hypertension
Authors: Craig Michael W. Millar , Mann Stewart , Balasubramanian V. , Raftery E. B.
Published: August 2015

1. Both systolic and diastolic blood pressure show a well defined circadian variation in ambulatory hypertensive subjects.

2. Blood pressure is highest in the mid-morning (10.00 hours) and lowest during sleep at 03.00 hours.

3. Treatment with oxprenolol (taken during the day) reduces daytime blood pressure but is less effective during the night and early morning.
Pseudohypertension in the Elderly
Authors: Spence J. D. , Sibbald W. J. , Cape R. D.
Published: August 2015

1. Direct intra-arterial blood pressure (radial artery) has been compared with indirect blood pressures using a regular sized adult cuff and a thigh cuff, with a mercury sphygmomanometer, in 24 hypertensive patients aged 62–84 years, and in 16 hypertensive patients aged 29–59 years.

2. The patients were studied because they were suspected of having a false elevation of their indirect blood pressure, since they had diastolic pressures over 100 mmHg, without hypertensive retinopathy, cardiac hypertrophy, or nephropathy.

3. Indirect diastolic pressure was falsely elevated by 30 mmHg or more in 12 out of 24 of the subjects over age 60, and in four of the 16 of those under age 60. Pseudohypertension (indirect diastolic > 100 mmHg, direct diastolic < 90 mmHg) was present in 12 subjects over age 60 and 5 under age 60.

4. Errors in indirect measurement of blood pressure are a serious problem, particularly in the elderly. Direct intra-arterial measurement may be useful in the management of hypertension.
Hepatic Binding Sites for Angiotensin II in the Rat
Authors: Lafontaine J. J. , Nivez M. P. , Ardaillou R.
Published: August 2015

1. 125I-labelled (Asn1, Val5)-angiotensin II (125I-labelled AII) incubated with purified rat liver membranes was degraded with time, as estimated by three techniques: binding to an excess of specific antibody, polyacrylamide-gel electrophoresis and rebinding to fresh membranes. Degradation was inhibited in the presence of an excess of β1–24-corticotrophin but still very marked.

2. 125I-labelled AII became bound to purified rat liver membranes. Association and dissociation rates were slow. Binding was competitively inhibited by (Asn1, Val5)-AII, (Asp1, Ile5)-AII and (Des, Asn1, Ile5)-AII. Apparent KD was approximately 0·1 nmol/l.

3. Bound hormone was also partly degraded independently of time.

4. Angiotensinases inhibitors had different effects on 125I-labelled AII binding. A clear increase was observed in the presence of β1–24-corticotrophin and phenylmethylsulphonylfluoride whereas binding was decreased in the presence of EDTA or 8-hydroxyquinoline.

5. These results demonstrate the presence of high-affinity binding sites for AII and of angiotensinases in hepatic membranes.
Erythrocyte δ-aminolaevulinic Acid Dehydratase Activity and Blood Protoporphyrin Concentrations as Indices of Lead Exposure and Altered Haem Biosynthesis
Authors: Meredith P. A. , Moore M. R. , Goldberg A.
Published: August 2015

1. The activity of erythrocyte δ-aminolaevulinic acid (ALA) dehydratase and blood protoporphyrin concentrations have been measured in patients with various anaemias, a group of subjects with known lead exposure and a group of control subjects. Leucocyte ALA synthase was measured in subjects from the last two groups.

2. Erythrocyte ALA dehydratase activity was significantly depressed in the group of lead-exposed subjects and showed a highly significant negative exponential relationship with blood lead concentration.

3. Blood protoporphyrin concentrations were significantly elevated in the group of lead-exposed subjects and patients with iron-deficiency anaemia and showed a significant positive exponential relationship with blood lead concentration.

4. Comparison of the least-squares regression analysis of these relationships and incidence of false positive and false negative results indicates that erythrocyte ALA dehydratase activity is a more accurate measure of environmental and moderate industrial lead exposure than blood protoporphyrin concentrations.

5. The correlations of erythrocyte ALA dehydratase and leucocyte ALA synthase activity, and of blood protoporphyrin concentrations and leucocyte ALA synthase activity, suggest that blood protoporphyrin more accurately reflects haem synthesis than does erythrocyte ALA dehydratase activity.
The Influence of Ammonia and Octanoic Acid on Liver Regeneration in the Rat
Authors: Ellis W. R. , Chu P. K. , Murray-Lyon I. M.
Published: August 2015

1. We have investigated the effect of intermittent doses of ammonia and octanoic acid on liver regeneration in the rat after partial hepatectomy. Regeneration was assessed by uptake of tritiated thymidine into liver deoxyribonucleic acid.

2. We have found a reduction in hepatic regenerative response in animals treated with ammonium acetate as a source of ammonia.

3. No inhibiting effect of octanoic acid on liver regeneration was found, at the dose used.

4. The implications of the results for management of fulminant hepatic failure are discussed.
Metabolism of Infused L(+)-Lactate during Exercise
Authors: Ryan W. J. , Sutton J. R. , Toews C. J. , Jones N. L.
Published: August 2015

1. The ability to metabolize lactate at rest and during exercise was studied in six male subjects by using a constant infusion of sodium l(+)-lactate at a rate of 0·05 mmol min−1 kg−1. Twenty minute periods of rest and exercise at two work rates were used, amounting to 25% and 50% of maximal O2 uptake (V̇o2 max.) in four subjects and 50% and 66% of V̇o2 max. in two subjects. Control measurements were made with saline infusion. In all studies a steady state in blood lactate was achieved.

2. At rest lactate infusion was associated with an increase of 3·51 mmol/l (± sd 0·70) in plasma lactate. The increase was smaller in exercise and in a given subject was the same at both work rates; plasma lactate was on average 1·21 mmol/l (±sd 1·11) higher during lactate infusion than the control measurement at the same power output. In one subject lactate values in exercise were unchanged by lactate infusion.

3. At rest lactate infusion was associated with an increase in O2 intake and CO2 output, the respiratory exchange ratio was unchanged, and plasma HCO−3 rose by 1·85 mmol/l.

4. During exercise lactate infusion was associated with a smaller and variable increase in O2 intake. CO2 output was less, the respiratory exchange ratio fell, and plasma HCO−3 rose by 6·1 mmol/l.

5. Exercise is accompanied by an increased capacity to metabolize lactate aerobically. Decreasing lactate metabolism appears to play no part in the increase in plasma lactate concentration with increasing exercise, at least to 66% of the maximal O2 intake.
Pregnancy-Associated Disease of the Renal Microcirculation
Authors: Al-Khader A. A. , Stewart Christine , Aber G. M.
Published: August 2015

1. Platelet factor 3, platelet survival, renal platelet localization and fibrinolytic activity have been studied in normotensive subjects with a previous history of pregnancy-associated hypertension. Studies were carried out up to 6 years after the complicated pregnancy.

2. Renal platelet localization was found to be significantly increased despite normal platelet survival and platelet factor 3 availability. Significant impairment of both resting and post-venous-occlusion fibrinolytic activity was also demonstrable.

3. The significance of these findings in relation to mediation of progressive intrarenal vascular disease is discussed.
The Pattern of Breathing in Patients with Chronic Airflow Obstruction
Authors: Garrard C. S. , Lane D. J.
Published: August 2015

1. The pattern of breathing in 12 patients with severe irreversible airflow obstruction has been studied during ventilatory stimulation by rebreathing CO2. Mean maximum tidal volume response was only 1·23 ± 0·30 litres (mean ± sd); this represented 65% of mean measured vital capacity and 82% of mean measured inspiratory capacity. During the course of rebreathing mean total breath duration was reduced from 3·48 ± 0·93 to 2·44 ± 0·48 s.

2. End-expiratory thoracic gas volume (FRC) was elevated at rest in all subjects and increased significantly by a further 0·50–1·90 litres during ventilatory stimulation in 10 of the 12 subjects. The maximum increase in FRC was proportional to the degree of airflow obstruction afforded by the airways in each subject.

3. It is suggested that the increase in FRC during ventilatory stimulation is responsible for the diminished tidal volume response and is an important determinant of breathing pattern and symptomatology in patients with airflow obstruction.
Acyl-Coenzyme A—Cholesterol Acyltransferase Activity in Human Liver
Authors: Balasubramaniam S. , Mitropoulos K. A. , Myant N. B. , Mancini M. , Postiglione A.
Published: August 2015

1. In the presence of CoA and ATP, human liver microsomes catalyse the incorporation of [14C]oleate or [14C]cholesterol into cholesteryl oleate, thus demonstrating the presence of acyl-coenzyme A-cholesterol acyltransferase (cholesterol acyltransferase) in human liver.

2. The enzyme has properties similar to those of rat liver enzyme and with both the concentration of endogenous cholesterol in the microsomal fraction is adequate to support a constant initial rate of esterification. However, unlike the rat liver enzyme, the human cholesterol acyltransferase does not efficiently utilize added cholesterol as substrate.

3. The activity of cholesterol acyltransferase in human liver was 25% of that measured in rat liver under similar conditions of assay.
Influence of Angiotensin II, Ouabain and Hydrostatic Pressure on Inulin and Electrolyte Concentration of Fluid Perfusing Pig Carotid Arteries in Vitro
Authors: Healy J. K. , Elliott A. J. , Oweczkin I. J.
Published: August 2015

1. Angiotensin II was infused into isolated, perfused pig carotid arteries. The perfusate leaving the arteries was sampled into an Auto-analyzer system which continuously monitored its composition. Arterial pressure was recorded.

2. Low, subpressor doses of angiotensin II raised the perfusate potassium concentration, whereas high doses, which produced contraction, lowered perfusate potassium and sodium concentrations. Inulin and chloride concentrations did not change.

3. The elevation of perfusate potassium with low angiotensin II dosage was appreciable compared with that caused by high doses of ouabain.

4. Neurotransmitter blockade did not alter the low- and high-dose angiotensin II effects. In other sequential dose studies, valine5-angiotensin II and isoleucine5-angiotensin II did not differ in their effects on perfusate composition or arterial contraction.

5. Mechanically increased hydrostatic pressure lowered perfusate sodium concentration, so that increased arterial pressure might have contributed to this aspect of high-dose angiotensin II effects.

6. These effects of angiotensin II might have physiological significance in relation to arterial smooth muscle and to electrolyte homeostasis.
A Defect in Zinc Uptake by Jejunal Biopsies in Acrodermatitis Enteropathica
Authors: Atherton D. J. , Muller D. P. R. , Aggett P. J. , Harries J. T.
Published: August 2015

1. In a system in vitro, 65Zn accumulation by jejunal mucosal biopsies from patients with acrodermatitis enteropathica was found to be markedly reduced compared with controls.

2. We suggest that defective uptake of zinc by enterocytes is the primary abnormality responsible for the zinc deficiency underlying this disorder.
Lecithin—Cholesterol Acyltransferase and the Lipoprotein Abnormalities of Parenchymal Liver Disease
Authors: Day R. C. , Harry D. S. , Owen J. S. , Foo A. Y. , McIntyre N.
Published: August 2015

1. Detailed studies have been made of the plasma lipoprotein abnormalities in parenchymal liver disease to test the hypothesis that the abnormalities would correlate with plasma lecithin-cholesterol acyltransferase (LCAT) activity.

2. When LCAT was high, very-low-density-lipo-proteins (VLDL) were normal in composition and had a normal pre-β electrophoretic mobility. When LCAT was low, VLDL concentrations were greatly reduced.

3. With high LCAT low-density lipoproteins (LDL) were normal. The LDL particles found with low LCAT activity were of normal size but of abnormal composition, being triglyceride rich and cholesteryl ester poor. Regardless of LCAT activity LDL were present in normal amounts.

4. High-density lipoproteins (HDL) were normal in composition and electron-microscopic appearance when LCAT activity was high. When LCAT activity was low HDL were abnormal in composition and ‘stacked discs’ were seen on electron microscopy.

5. These results suggest that low LCAT activity may be the cause of at least some of the lipoprotein changes of parenchymal liver disease.
Effects of an Orally Active Converting-Enzyme Inhibitor, SQ 14225, on Pressor Responses to Angiotensin Administered into the Brain Ventricles of Spontaneously Hypertensive Rats
Authors: Mann J. F. E. , Rascher W. , Dietz R. , Schömig A. , Ganten D.
Published: August 2015

1. Two hours after oral feeding of normotensive Wistar Kyoto rats with the converting-enzyme inhibitor SQ 14225 (1 and 10 mg/kg), an increase of angiotensin I plasma concentrations from 892 ± 113 to 1660 ± 167 and 2951 ± 405 pg/ml was observed.

2. Administration of SQ 14225 with the drinking fluid overnight suppressed the pressor responses to intravenous angiotensin I, although the blood pressure increase after intravenous angiotensin II was not altered in normotensive and spontaneously hypertensive rats. No change of pressor effects after injections of angiotensin I and II into the brain ventricles was observed after oral SQ 14225.

3. Intracerebroventricular infusions of SQ 14225 in spontaneously hypertensive rats abolished the central pressor responses to angiotensin I.

4. The results show that SQ 14225 effectively blocked the conversion of endogenous and exogenous angiotensin I into angiotensin II in plasma, and the conversion of exogenous angiotensin I in brain. Under the conditions studied, SQ 14225 does not cross the blood-cerebrospinal fluid barrier in spontaneously hypertensive rats.
Accidental Hypothermia and Rewarming in Dogs
Authors: Auld C. D. , Light I. M. , Norman J. N.
Published: August 2015

1. Twenty lightly anaesthetized dogs were cooled to 29°C by cold-water immersion. Ventilation was spontaneous and the animals were allowed to shiver freely. Metabolic heat production and respiratory heat exchange were measured during rewarming.

2. The animals were divided into four groups each of five dogs and each group was rewarmed by a different technique. The control group was allowed to rewarm spontaneously; a second group was given warm (45–50°C) fully humidified air to breathe in addition; a third group was rewarmed in a hot-water bath (42–44°C) and the remaining group was given a muscle relaxant to abolish shivering and rewarmed by warm inspired air only.

3. The group rewarmed in hot water achieved normal core temperature most rapidly but there was no difference in the rewarming rates of the group rewarmed spontaneously and of the group given warm air to breathe in addition.

4. The group given a muscle relaxant and rewarmed with warm inspired air required 12 h to achieve the same core temperature as the shivering groups achieved in 2 h. Compared with the heat produced by shivering the amount of heat which it was possible to transfer across the respiratory tract was so small that it did not materially influence the rate of rewarming.
Brain Angiotensin II Binding and Central [Sar1,Ala8]Angiotensin Responses in Normal Rats and the New Zealand Strain of Genetically Hypertensive Rats
Authors: Sirett Nancy E. , Thornton S. N. , Hubbard J. I.
Published: August 2015

1. Specific angiotensin II (ANGII) receptor binding was measured in regions of the brains of the New Zealand genetically hypertensive and normal rats.

2. ANGII receptor binding was consistently lower in the septum, midbrain, thalamus and posterior medulla of the genetically hypertensive rats than in normal rats.

3. Blood pressure responses to intraventricular injections of ANGII and an ANGII antagonist [Sar1,Ala8]angiotensin were studied in conscious and pentobarbitone-anaesthetized genetically hypertensive and normal rats. In conscious rats no significant difference between the two strains of rat was detected.

4. In pentobarbitone-anaesthetized rats intraventricular injection of 40 μg of [Sar1,Ala8]angiotensin had a hypotensive effect which was three times greater in the genetically hypertensive rats than that observed in normal rats. The latency of this hypotensive effect was longer than the latency of the hypertensive effect of ANGII.

5. The drinking responses to intraventricular injections of ANGII were similar in genetically hypertensive and normal rats.

6. The physiological role of the ANGII system is discussed and it is concluded that an abnormality of this system in the brain may well be responsible for the hypertension found in the genetically hypertensive rat.
Effects of Diphosphonate and Colchicine Administration upon Acid–Base Changes Induced in Rats by Bilateral Nephrectomy
Authors: Goulding Ailsa , Broom M. F.
Published: August 2015

1. The effects of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) and colchicine on acid-base balance were examined in intact and nephrectomized rats.

2. Both drugs increased extracellular hydrogen ion concentrations and depressed extracellular bicarbonate concentrations in nephrectomized rats compared with controls but did not alter these parameters in intact animals.

3. Intracellular hydrogen ion concentrations in the skeletal muscle of nephrectomized rats given EHDP were higher than those of control animals.

4. It is postulated that colchicine and EHDP inhibit skeletal buffering of non-volatile acids produced endogenously in nephrectomized rats.
Clinical and Electrophysiological Studies of Peripheral Nerve Function in Patients with Chronic Liver Disease
Authors: Morgan M. H. , Read A. E. , Campbell M. J.
Published: August 2015

1. A series of 24 (eight alcoholic, 16 non-alcoholic) patients with histologically confirmed cirrhosis of the liver was examined for clinical and electrodiagnostic evidence of peripheral nerve damage.

2. Clinical evidence of mild, asymptomatic peripheral neuropathy was found in only three (19%) of the non-alcoholic group.

3. Electrodiagnostic tests on the median, ulnar, lateral popliteal and sural nerves were undertaken for each patient. Abnormalities of distal motor latency, motor conduction velocity or sensory action potential amplitudes were noted in 17 (71%). Exclusion of three patients in whom abnormality was confined to the median nerve, with the possibility of carpal tunnel compression, gave a final overall figure of 14 (58%). In the non-alcoholic group there were ten (63%) with abnormalities.

4. Sensory action potential amplitudes were reduced in 16 (67%), but only eight (33%) had abnormal distal motor latencies or motor conduction velocities. Nerves were affected in a patchy and unpredictable manner.

5. The number of abnormal electrodiagnostic tests for each patient bore no direct relation to the length of history, nor to the severity of liver damage.

6. In a selected group of patients with no other demonstrable cause of peripheral nerve damage, there was a positive correlation between the number of abnormal electrodiagnostic tests and the degree of slowing of the EEG mean dominant frequency. Possible implications of this finding are discussed.
Antihypertensive Effect of Prolonged Blockade of Angiotensin Formation in Benign and Malignant, one- and two-Kidney Goldblatt Hypertensive Rats
Authors: Bengis R. G. , Coleman T. G.
Published: August 2015

1. The effect of chronic inhibition of angiotensin II formation was investigated in four groups of hypertensive rats. Benign hypertension was produced by placing a 0·25 mm-diameter silver clip on the renal artery; a 0·20 mm clip was used to create malignant hypertension. A two-kidney model had a clip plus intact contralateral kidney and a one-kidney model had a clip plus contralateral nephrectomy. Benign and malignant groups were prepared in both the one-kidney and two-kidney variations. Converting enzyme inhibitor (SQ 14.225) was given to these four groups for 1 week in drinking water and average intake ranged from 33 to 77 mg/day.

2. The two malignant groups had the highest plasma renin activities and they showed a precipitous fall in arterial pressure in the first 24 h of inhibition of angiotensin formation. All groups showed an additional slow decline in pressure during the remaining 6 days of inhibition. Changes in heart rate and sodium excretion were variable but, in general, heart rate decreased during inhibition.

3. Arterial pressure did not become normal with inhibition in either of the one-kidney models: decreases to 126 and 132 mmHg were observed in the benign and malignant groups respectively. Three of the malignant one-kidney animals became uraemic with inhibition and one died before inhibition was discontinued.

4. Arterial pressure was reduced to normal pressure (95 mmHg) after 1 week of inhibition in both the benign and malignant two-kidney models.

5. It appears that normal pressure was restored in the two-kidney model but not in the one-kidney model because of the presence of the intact contralateral kidney. The physiological basis for this difference is not known but changes in renal excretory function may be involved.
An 8 Month Longitudinal Study of Changes in Elastic and Muscular Arteries and Veins of the Rabbit with Sustained Hypertension after Abdominal Aorta Constriction
Authors: Bevan R. D. , Eggena P. , Hume W. R. , Lais L. T. , Van Marthens E. , Bevan J. A.
Published: August 2015

1. Long-term changes in the function and structure of arteries and veins in response to an elevation in arterial pressure have been studied in the rabbit after partial abdominal aorta constriction.

2. Transient changes occur in the vasculature in association with the rise in arterial pressure.

3. The dominant change seen after arterial pressure elevation has been maintained for 8 months is an increase in arterial wall mass, including an increase in vascular smooth muscle cell number, and in some arteries an increase in internal diameter.

4. It may be inferred from this limited study of elastic and muscular arteries that structural alteration represents the over-riding response of the vasculature to an elevation in intramural pressure.
The Composition of Low-Density Lipoprotein and Very-Low-Density Lipoprotein Subfractions in Primary Hypothyroidism and the Effect of Hormone-Replacement Therapy
Authors: Ballantyne Fiona C. , Epenetos A. A. , Caslake Muriel , Forsythe S. , Ballantyne D.
Published: August 2015

1. The lipid and protein composition of subfractions of plasma low-density lipoprotein (LDL) has been determined in nine patients with primary hypothyroidism before and after 3 months of thyroxine therapy. Analyses were also made of subfractions of very-low-density lipoprotein (VLDL) in four of the patients.

2. Before therapy seven of the patients had elevated LDL-cholesterol and two had increased VLDL-cholesterol concentrations. On thyroxine replacement the mean LDL-cholesterol fell to normal. No significant change occurred in the concentration of cholesterol in VLDL or in high-density lipoprotein (HDL).

3. The concentrations of cholesterol, triglyceride and apolipoprotein B (apoB) were increased in the LDL subfraction of Sf 10·4–20, which corresponds mainly to intermediate-density lipoprotein. This subfraction showed a marked fall on therapy. The cholesterol and apoB concentrations in the major LDL fraction of Sf 5·7–12 also decreased on therapy, but the fall in the subfraction of Sf 3·5–6·5 did not reach statistical significance.

4. Only the VLDL subfraction of smallest size (Sf 20–60) had any abnormality before therapy, with an increased concentration of cholesterol. On thyroxine the concentration of triglyceride rose in the VLDL subfractions.

5. These data suggest that thyroxine exerts its major effect on lipoprotein metabolism by promoting the conversion into LDL of intermediate-density lipoprotein, formed by catabolism of VLDL.
Effect of 1 Year's Therapy in Essential Hypertension on Systemic Haemodynamics Studied before and after ‘Total’ Autonomic Blockade
Authors: Jennings G. L. , Korner P. I. , Esler M. D.
Published: August 2015

1. The haemodynamics of ten patients with essential hypertension were studied before treatment (study 1) and again 1 week after cessation of 1 year's antihypertensive drug therapy (study 2). On each occasion measurements of mean arterial pressure (MAP), cardiac index (CI) and total peripheral resistance index (TPRI) were made before and after ‘total’ pharmacological autonomic blockade (with intravenous propranolol, atropine, phentolamine and clonidine); measurements after ‘total’ autonomic blockade were used to assess the magnitude of the ‘non-autonomic’ component of TPRI, which reflects humoral or structural alterations in the vasculature.

2. The findings before ‘total’ autonomic blockade during study 2 showed that MAP was 18 ± 8 mmHg below the value (135 mmHg) observed during study 1 before treatment, and TPRI had fallen by 33% (P < 0·05) and CI had increased by 23% (P < 0·05).

3. After ‘total’ autonomic blockade the differences in the ‘non-autonomic’ components of the different variables were similar, with ‘non-autonomic’ MAP 14 ± 4 mmHg lower in study 2, TPRI 42% lower (P < 0·005) and CI 28% higher. The value in ‘non-autonomic’ TPRI was now the same as values previously observed in normotensive subjects.

4. We conclude that after 1 year's successful treatment there is complete restoration of ‘non-autonomic’ TPRI as a secondary consequence of the blood pressure reduction.
Dependence of Deoxycorticosterone/Salt Hypertension in the Rat on the Activity of Adrenergic Cardiac Nerves
Authors: Bell C. , McLachlan Elspeth M.
Published: August 2015

1. Chronic hypertension was induced in Wistar rats with intact kidneys by subcutaneous implantation of 50 mg of deoxycorticosterone acetate (DOC A) in wax and addition of sodium chloride (9 g/l) to the drinking water.

2. The development of DOCA/salt hypertension, as monitored by tail-cuff plethysmography, was prevented by: (a) destruction of the peripheral adrenergic nerves with neonatal administration of guanethidine (80 mg/kg subcutaneously for the first 14 days postnatally); (b) bilateral stellate ganglionectomy; (c) oral administration of the β-adrenoreceptor antagonists propranolol or atenolol (1 mg day−1 kg−1) during the period of DOCA/salt treatment.

3. The dose of DOCA used was sufficient to inhibit the atrial Uptake2 pathway completely: this process appears to participate in termination of action of neurally released noradrenaline in the heart.

4. It is suggested that this model of DOCA/salt hypertension is due to adrenergic enhancement of cardiac output in the presence of an increased sodium load. The enhancement may be partly due to deficient myocardial inactivation of noradrenaline.
Comparison of 15N-Labelled Glycine, Aspartate, Valine and Leucine for Measurement of Whole-Body Protein Turnover
Authors: Taruvinga M. , Jackson A. A. , Golden M. H. N.
Published: August 2015

1. Whole-body protein turnover was measured in rats by constant infusion of 15N-labelled glycine, aspartate, valine and leucine and measuring the enrichment of hepatic and renal urea and ammonia nitrogen.

2. The values obtained with [15N]glycine were comparable with values reported with methods based on different assumptions.

3. [15N]Aspartate gave rise to an increased enrichment of urea and ammonia and hence to lower protein-turnover rates.

4. [15N]Valine and [15N]leucine gave low enrichments of nitrogenous end products and hence to high protein-turnover rates.

5. All 15N-labelled amino acids are not equally suitable for measuring whole-body protein turnover by the end-product method. The relative amounts of 15N going to the end products can be predicted from the known individual metabolism of aspartate and the branched-chain amino acids.
The Adenylate Cyclase System in Human Liver: Characterization, Subcellular Distribution and Hormonal Sensitivity in Normal or Cirrhotic Adult, and in Foetal Liver
Authors: Pecker F. , Duvaldestin P. , Berthelot P. , Hanoune J.
Published: August 2015

1. Adenylate cyclase (EC 4.6.1.1) activity was characterized in human liver, and its subcellular distribution compared with that of three other potential enzyme markers of the pericellular membrane: leucine aminopeptidase (EC 3.4.11.1), γ-glutamyltransferase (EC 2.3.2.2) and 5′-nucleotidase (EC 3.1.3.5). Although these three enzyme activities were detected in each of the subcellular fractions studied, 85% of the total adenylate cyclase activity was found in the 1000 g pellet (‘nuclear’ fraction) with a threefold increase in specific activity as compared with the homogenate. No adenylate cyclase activity existed in the 150 000 g supernatant fraction.

2. In the ‘nuclear’ fraction, adenylate cyclase activity was increased in a dose-dependent fashion by glucagon with a half-maximal stimulation at 10 nmol/l and a maximal four- to seven-fold increase at 1 μmol/l. Catecholamines activated adenylate cyclase 2·5- to three-fold, with an order of potency (protokylol > isoprenaline > adrenaline > noradrenaline) typical of a β2-adrenoreceptor. Prostaglandin E1 and NaF also stimulated cyclase two- and four-fold respectively. Insulin, serotonin, dopamine, thyroid-stimulating hormone and ACTH had no effect. Adenosine provoked a weak inhibition at 0·1 mmol/l. Finally guanosine triphosphate and 5′-guanylyl imidodiphosphate induced a marked increase in basal activity, four- and eight-fold respectively, but both reduced the relative increase in enzyme activity due to glucagon or adrenaline.

3. Cyclase from foetal liver (12–16 weeks old) and cirrhotic adult liver appeared to behave similarly to that from normal liver; however, foetal cyclase was more active, and cirrhotic enzyme less active than normal adult liver. Both systems responded to catecholamines via a β2-adrenoreceptor.

4. These results validate the use of rat liver adenylate cyclase as a tool for pharmacological and physiological studies.
Effect of Isoprenaline on the Plasma Concentrations of Angiotensin III in Rats
Authors: Meyer D. K. , Eisenreich M. , Nutto D.
Published: August 2015

1. A new column-chromatographic method is described for the simple and reproducible determination of the concentration of [des-Asp1] angiotensin II (angiotensin III) in rat plasma.

2. The method uses the different abilities of the ion-exchange resins Dowex 1 (X8) and Bio Rex 70 to bind angiotensin II and angiotensin III. Under the conditions used, Bio Rex 70 binds only angiotensin III. Angiotensin II and its hexapeptide metabolite [des-Asp1,des-Arg2]angiotensin II pass the resin with the effluent. Dowex 1 (X8) binds angiotensin II and the hexapeptide metabolite, whereas it does not extract angiotensin III. It does not separate angiotensin II from the hexapeptide. Therefore the sum of both peptides is expressed as angiotensin II-like activity. The ratio of the concentrations, angiotensin II/hexapeptide, was 5:1.

3. In normal rats the plasma concentration of angiotensin III was 20 fmol/ml (sd 15; n = 8), and angiotensin II-like activity was 60 fmol/ml (sd 35; n = 8).

4. The β-sympathomimetic amine isoprenaline caused a time- and dose-dependent increase in plasma angiotensin III and angiotensin II-like activities.

5. Under the conditions studied angiotensin III contributed approximately 25% to the total amount of angiotensins in plasma.
Dissociation in the Excretion of Different Aldosterone Metabolites and Unmetabolized (‘Free’) Aldosterone in Hypertension
Authors: Abdelhamid S. , Vecsei P. , Haack D. , Gless K.-H. , Walb D. , Lichtwald K. , Fiegel P.
Published: August 2015

1. The determination of aldosterone-18-glucuronide (pH 1-labile aldosterone) was complemented by concomitant measurements of free urinary aldosterone and tetrahydroaldosterone in 307 patients, most of whom were hypertensive. In 38 cases (12·3%) the normal, aldosterone-18-glucuronide concentration was clinically misleading, but increased free aldosterone and/or tetrahydroaldosterone values suggested the presence of hyperaldosteronism, which in many of these cases was confirmed by elevated excretion of the possible major aldosterone precursor 18-hydroxycorticosterone (18-OH-B).

2. Of 224 patients with essential hypertension and normal or low plasma renin activity 18 had an elevated free aldosterone and/or tetrahydroaldosterone excretion without increased aldosterone-18-glucuronide. These cases may represent early or pre-symptomatic forms of primary hyperaldosteronism. In other cases, particularly when tetrahydroaldosterone was increased alone, abnormalities of aldosterone metabolism were suspected.

3. In two out of 15 patients with primary hyperaldosteronism, aldosterone-18-glucuronide values were frequently found to be normal, although elevations were noted in other variables. However, no relation to the morphological abnormality (adenoma versus hyperplasia) was seen.
Effect of Ouabain in Therapeutic Concentrations on K+ Exchange and Contraction of Human and Rabbit Myocardium
Authors: Poole-Wilson P. A. , Galindez E. , Fry C. H.
Published: August 2015

1. Experiments were undertaken on strips of human atrial and ventricular muscle, on right ventricular rabbit papillary muscles and on the rabbit interventricular septum.

2. In all preparations an increase of developed tension after 30 min exposure to ouabain was apparent only at or above a concentration of 10−7 mol/l (73 μg/l).

3. In the rabbit septum there was a net loss of potassium on exposure to ouabain if the concentration was greater than 10−7 mol/l. There was no net loss, or gain, of potassium at lower concentrations. Loss of potassium, indicating inhibition of the sodium pump, could not be dissociated from the positive inotropic effect of ouabain.

4. The greater sensitivity to ouabain of human myocardium in vivo (10−8 mol/l) than in vitro (10−7 mol/l) may be due to cellular changes occurring in isolated preparations.
Are Mineralocorticoid Receptors Present in Human Renal Adenocarcinoma?
Authors: Rafestin-Oblin M. E. , Roth-Meyer C. , Claire M. , Michaud A. , Baviera E. , Brisset J. M. , Corvol P.
Published: August 2015

1. The presence of high-affinity sites for [3H]-aldosterone was shown in the normal human renal tissue.

2. [3H]Aldosterone and [3H]dexamethasone binding were studied in human renal adenocarcinoma and in uninvolved external cortex, in 22 patients undergoing nephrectomy for renal adenocarcinoma. Tissue incubations were performed with either [3H]aldosterone (5 × 10−10 mol/l; 5 × 10−9 mol/l in the presence of unlabelled glucocorticoids) or [3H]dexamethasone (5 × 10−9 mol/l).

3. Cytosol [3H]aldosterone binding was six- to seven-fold lower (P < 0·001) in neoplastic than normal tissue. [3H]Dexamethasone binding was about twofold higher in neoplastic than in normal tissue. This difference was not significant.

4. Nuclear uptake experiments showed that, both in cytosol fractions and nuclei, [3H]aldosterone binding was lower in adenocarcinoma than in normal cortex.

5. The very low binding of [3H] aldosterone suggests that mineralocorticoid receptors are absent in renal adenocarcinoma, an hypothesis in line with the proximal origin of these tumours.
Distribution of Circulating Immunoreactive Components of Parathyroid Hormone in Normal Subjects and in Patients with Primary and Secondary Hyperparathyroidism: The Role of the Kidney and of the Serum Calcium Concentration
Authors: Dambacher M. A. , Fischer J. A. , Hunziker W. H. , Born W. , Moran J. , Roth H.-R. , Delvin E. E. , Glorieux F. H.
Published: August 2015

1. The distribution of intact parathyroid hormone-(1–84) [PTH-(1–84)] and of its COOH-terminal fragments was determined in human serum by column chromatography. In addition to PTH-(1–84) (peak I), COOH-terminal fragments having molecular weights of approximately 4000–7000 (peak II) and immunoreactive components co-eluting with human PTH-(1–12) (peak III) were observed.

2. Mean concentrations of intact PTH-(1–84) and of its COOH-terminal fragments were significantly raised in chronic renal failure as compared with those of normal subjects. Mean amounts of peak II were higher in patients with chronic renal insufficiency than in nutritional vitamin D deficiency, in pseudohypoparathyroidism and in primary hyperparathyroidism, despite comparable amounts of PTH-(1–84).

3. In chronic renal failure as well as in a group of patients with vitamin D deficiency, pseudohypoparathyroidism and primary hyperparathyroidism and in controls, significant linear relations were found between the serum concentrations of calcium and log (peak II/peak I). Our findings suggest that the conversion of intact PTH-(1–84) into COOH-terminal fragments by the parathyroid glands (resulting in a raised secretion of fragments) and/or in peripheral organs may be directly related to the serum concentration of calcium. However, the degradation of the fragments may also be suppressed in a calcium-dependent manner.
Effect of Age on Noradrenaline Sensitivity of Mesenteric Resistance Vessels in Spontaneously Hypertensive and Wistar—Kyoto Rats
Authors: Mulvany M. J. , Aalkjær C. , Christensen J.
Published: August 2015

1. We have compared the noradrenaline sensitivity of 150 μm arterial resistance vessels taken from a specific place in the mesenteric bed of spontaneously hypertensive (SH) rats and of control Wistar—Kyoto (WK) rats at three ages: 6 weeks, 12 weeks and 24 weeks.

2. The noradrenaline sensitivity of the vessels under normal conditions was the same at all ages in both SH and WK rats (ED50 about 3 μmol/l).

3. After addition of cocaine (which inhibits the uptake of noradrenaline in the nerve terminals) all vessels became more sensitive to noradrenaline, but at all ages the increase in sensitivity was greater in the vessels of SH rats, suggesting that the smooth muscle cells in these vessels had a greater intrinsic noradrenaline sensitivity than the vessels of WK rats.

4. Since elevation of the blood pressure in the SH rats occurs mainly between the ages of 6 and 12 weeks, the results suggest that the greater intrinsic smooth muscle cell sensitivity of the SH rat vessels is a factor which is amongst the primary factors responsible for the development of hypertension in the SH rat.
Pressor Responsiveness to Angiotensin in Renovascular and Steroid Hypertension
Authors: Marks E. S. , Thurston H. , Bing R. F. , Swales J. D.
Published: August 2015

1. The pressor response to angiotensin II was reduced in rats with early (<6 weeks) and chronic (>4 months) Goldblatt two-kidney, one-clip hypertension and enhanced in DOCA—salt hypertension.

2. Converting enzyme inhibition with captopril brought the angiotensin pressor response curves into closer proximity although the DOCA hypertensive rats were minimally hyper-responsive and rats with early and chronic renovascular hypertension showed slightly reduced responsiveness.

3. After bilateral nephrectomy the pressor responses to angiotensin were similar.

4. The pressor response to angiotensin II in these animals was inversely related to plasma renin concentration and therefore largely dependent upon receptor occupancy by endogenous angiotensin II. There is no evidence for enhanced pressor responsiveness to angiotensin in either renovascular or DOCA hypertension.
Radiolabelled Bile Acid Clearance in Control Subjects and Patients with Liver Disease
Authors: Engelking L. R. , Barnes S. , Dasher C. A. , Naftel D. C. , Hirschowitz B. I.
Published: August 2015

1. The serum bile acid disappearances of tracer doses of [24-14C]cholic acid and [1-14C]-glycocholic acid were studied in eight normal subjects and 11 patients with chronic liver disease (with or without cholestasis) in order to determine the effect of liver disease on hepatic clearances, reflux of conjugated cholic acid and initial distribution volume of each tracer.

2. Total cholic acid clearance was significantly reduced from normal (7·2 ± 0·7 ml min−1 kg−1, mean ± se) in patients with liver disease (69–88%, group means) as were unconjugated cholic acid (51–68%) and glycocholic acid (66–83%) clearance.

3. Extensive regurgitation of labelled conjugated cholic acid (after unconjugated cholic acid tracer injection) among cholestatic patients accounted for 69 ± 5% of total 14C remaining in serum at 70 min, thus masking a less-impaired uptake process.

4. The hepatic extraction efficiency for conjugated cholic acid among controls (86 ± 8%) was greater than that for unconjugated cholic acid (60 ± 4%), and was greatly reduced among patients (7–27%, group means).

5. Normal subjects and patients with cirrhosis without cholestasis did not distribute the isotope to extravascular, extrahepatic spaces, in contrast to cholestatic patients with serum bile acid concentration > 149μmol/l.

6. Careful evaluation of serum disappearance of bile acids as well as chromatographic separation of regurgitated metabolites, could provide investigators with indirect evidence of defects in the rate-limiting steps (uptake, conjugation or excretion) of hepatic bile acid transport.