bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-Term Treatment of Hypertension in Man by an Orally Active Angiotensin-Converting Enzyme Inhibitor
Authors: Brunner H. R. , Gavras H. , Turini G. A. , Waeber B. , Chappuis P. , McKinstry D. N.
Published: August 2015

1. Captopril or SQ 14 225, administered orally twice a day, reduced the blood pressure of hypertensive patients whatever their clinical diagnosis and even when their plasma renin activity was ‘normal’ or low.

2. Long-term administration of captopril, either alone or together with diuretics, provides a powerful new tool with which to treat ambulatory hypertensive patients.

3. The renin system may play an important role in maintaining blood pressure in a majority of hypertensive patients.
β-Adrenoreceptor-Blocking Agents and Lipid Metabolism
Authors: England J. D. F. , Hua A. S. P. , Shaw J.
Published: August 2015

1. Chlorothiazide twice a day plus atenolol, metoprolol, pindolol and propranolol in single daily doses administered to patients with essential hypertension achieved effective control of blood pressure.

2. Each β-adrenoreceptor-blocking drug was associated with small, but significant, increases in plasma triglyceride concentrations and suppression of fasting immuno-reactive glucagon concentrations.
Low-density Lipoprotein Turnover Studies in Man. Evaluation of the Integrated Rate Equations Method, Use of a Whole-body Radioactivity Counter, and the Problem of Partial Denaturation
Authors: Calvert G. D. , James H. M.
Published: August 2015

1. We studied the turnover of low-density lipoprotein, density 1·031–1·056 kg/l, in five normal subjects and in four subjects with hyperlipoproteinaemia, using as tracer low-density lipoprotein labelled in the protein moiety with 131I. We analysed data derived with and without a whole-body radioactivity counter. Four models were used, including the integrated rate equations of Nosslin.

2. In most patients all methods gave similar results for the fractional catabolic rate. Use of the integrated rate equations allowed us to calculate the fractional catabolic rate in 3–5 days compared with 12 days for a multicompartmental method using plasma activity alone. The integrated rate equations method was valid only in a steady metabolic state, and could apparently be used when there was minor tracer denaturation. It was probably invalid when there was major partial tracer denaturation. The degree of partial denaturation could be estimated from the whole-body radioactivity graph. The whole-body counter was quick to use, required low levels of radioactivity and avoided error-prone urine collection.

3. Estimates of the relative size of the intravascular and extravascular compartments derived by five different methods were similar in studies in which there was insignificant denaturation of tracer.
Presence of Apolipoprotein-CII in Commercially available Albumin Fractions
Authors: Östlund-Lindqvist Ann-Margret , Boberg J.
Published: August 2015

1. Commercially available bovine serum albumin as Cohn fraction V was demonstrated to contain small amounts of apolipoprotein-CII.

2. This apolipoprotein activated lipoprotein lipase in the same way as apolipoprotein-CII purified from human very-low-density lipoproteins.
Loss of Metacarpal and Iliac Bone in Chronic Renal Failure: Influence of Haemodialysis, Parathyroid Activity, Type of Renal Disease, Physical Activity and Heparin Consumption
Authors: Henderson R. G. , Russell R. G. G. , Earnshaw M. J. , Ledingham J. G. G. , Oliver D. O. , Woods C. G.
Published: August 2015

1. Bone loss was assessed by measurement of cortical thickness of metacarpal bone by X-ray and of trabecular bone area in serial bone biopsies in 49 patients with chronic renal failure, six before and 45 during maintenance haemodialysis treatment.

2. Metacarpal cortical measurements (MCM) were very reproducible (coefficient of variation 1·95%), whereas bone area measurements by histology showed great variability. There was no correlation between rates of change of MCM and bone area over the same period, although both tended to fall with time.

3. The mean annual rate of bone loss measured by MCM for patients on dialysis was 2·08 ± 0·32 mm/year (mean ±1 sem) and this rate was not significantly different from the mean rate of loss of 2·49 ± 0·78 mm/year for the six patients who were not on maintenance haemodialysis. 61% of all patients showed a significant decrease during the period of study (1–6 years), but none had symptoms attributable to bone loss.

4. The loss tended to be greatest in women over the age of 40 years. The initial amount of bone and the rate of loss measured by MCM or bone histology were not influenced significantly by the presence or absence of histological or radiological evidence of parathyroid overactivity or of osteomalacia, nor by differences in the causes of renal disease.

5. Loss of metacarpal cortical bone correlated with heparin consumption during haemodialysis in men but not in women. The amount of bone and its rate of loss was not influenced by the presence of an arteriovenous shunt in one arm compared with the other. In neither sex did bone loss correlate with physical activity.

6. A relative deficiency of calcium due to a low dietary calcium intake and intestinal malabsorption of calcium, together with a dialysate calcium of only 1·5 mmol/l, may be more important causes of bone loss in patients in this study.
Sequential Enzyme and Subcellular Fractionation Studies on Jejunal Biopsy Specimens from Patients with Post-Infective Tropical Malabsorption
Authors: Peters T. J. , Jones P. E. , Wells G. , Cook G. G.
Published: August 2015

1. Jejunal biopsy specimens were obtained from seven patients with post-infective tropical malabsorption, four of whom were infected with Giardia lamblia.

2. Enzymic analysis of the biopsy homogenates revealed a selective reduction of certain enzymes (alkaline phosphatase, γ-glutamyl transferase) localized at least in part to the brush border. Other enzymes (leucyl-2-naphthylamidase, α-glucosidase) were unaffected.

3. Density gradient centrifugation confirmed the selective decrease in the brush-border activity but the equilibrium density of the organelle was normal. Homogenization studies revealed that the brush border was unusually fragile.

4. Apart from reduced activities of the basal—lateral marker enzyme 5′-nucleotidase and enhanced lysosomal fragility, other organelles showed normal properties. There were no significant differences in any of these parameters in the patients with or without giardiasis.

5. The patients were restudied after their jejunal morphology and clinical features had returned to normal. All these parameters, apart from a persistently reduced activity of 5′-nucleotidase, returned to normal.

6. It is suggested that the principal lesion in patients with post-infective tropical malabsorption affects the cell membrane, specifically affecting the absorptive—digestive capacity of the enterocyte. These findings suggest that there is direct brush-border damage rather than mucosal invasion by bacteria, viruses or Giardia lamblia.
l-Asparaginyl-Trna Synthetase and l-Asparagine Synthetase Activities of l-Asparaginase-Sensitive and -Resistant Forms of the Mouse Gardner Lymphoma 6C3HED
Authors: Davies M. R. , Lambert Lucy P. , Marshall R. D.
Published: August 2015

1. The mouse Gardner lymphoma 6C3HED was grown in ascites fluid in a form sensitive to the action of l-asparaginase (line 1), in another form which was resistant to l-asparaginase (line 2) and in a third form with partial sensitivity to l-asparaginase (line 3).

2. The l-asparaginyl-tRNA synthetase activities of extracts of the tumour cells, cultured both in the mouse and in vitro, were determined. Two of the lines, 1 and 3, in early passage numbers, showed a derepression mechanism involving l-asparagine. Mutation occurred with these lines resulting in the l-asparaginyl-tRNA synthetase activity of all the tumour cell lines being the same.

3. Cells of line 1 had low l-asparagine synthetase activity, which was unchanged by altering the supply of l-asparagine in vitro. Cells of lines 2 and 3 exhibited l-asparagine synthetase activities, which changed with the supply of l-asparagine.

4. It is not certain that l-asparagine synthetase activity of l-asparaginase-sensitive cells is controlled by l-asparaginyl-tRNA acting as a corepressor.
Effect of Intravenous Sodium Lactate on Renal Tubular Reabsorption of Phosphate in Man
Authors: Walton R. J.
Published: August 2015

1. The effects of sodium dl-lactate and sodium chloride (2·5 mg/kg as 865 mmol/l solutions given by intravenous infusion over 20 min) on the renal tubular reabsorption of phosphate have been compared in five normal adults.

2. Sodium lactate produced a marked but transient increase in urinary phosphate excretion due to a reduction in net renal tubular reabsorption of phosphate; the mean value of the maximum rate of renal tubular reabsorption of phosphate/unit of glomerular filtration rate (TmP/GFR) decreased from 1·14 to 0·82 mmol/l.

3. This effect was not due simply to expansion of the volume of the extracellular fluid, since the reduction in TmP/GFR after sodium chloride infusion was less marked, nor did it seem to be due entirely to alkalinization of the urine since the maximum increase in urinary pH occurred 20–40 min after the maximum decrease in TmP/GFR.
Protein Synthesis in Isolated Human Skeletal Muscle Tissue: Evaluation of an Experimental Model
Authors: Lundholm K. , Scherstén T.
Published: August 2015

Amino acids were incorporated into soluble proteins, myosin and myoglobin at constant rates for at least 4 h on incubation of isolated human skeletal muscle fibres. The time course of incorporation of leucine into proteins not attached to ribosomes was approximately constant, suggesting a continuous termination of proteins. A comparison between estimated pool size of ribosomes and incorporation rate of leucine into proteins indicated that initiation of peptides occurred even in the absence of insulin.
Effect of Indomethacin on Blood Pressure in the Normotensive Unanaesthetized Rabbit: Possible Relation to Prostaglandin Synthesis Inhibition
Authors: Colina-Chourio J. , McGiff J. C. , Nasjletti A.
Published: August 2015

1. To test the hypothesis that endogenous prostaglandins contribute to the regulation of blood pressure, we studied the effect of an inhibitor of prostaglandin synthesis, indomethacin, on mean aortic blood pressure in the normotensive, unanaesthetized rabbit.

2. Daily administration of indomethacin at 42 μmol/kg subcutaneously, but not of vehicle only, for 14 consecutive days, elevated the average mean arterial pressure in seven rabbits from 88 ± 3 mmHg on the last day of the control period to 105 + 3 mmHg (P < 0·01) and 107 ± 2 mmHg (P < 0·01) on days 6 and 14 of indomethacin treatment respectively, and reduced the urinary excretion of prostaglandin-like substance from 1·06 ± 0·26 to 0·17 ± 0·05 nmol of prostaglandin E2 equivalents/ day (P < 0·05; n = 5). Neither indomethacin nor the vehicle affected the intake of water, the 24 h urine volume, the cumulative difference between sodium intake and urinary sodium excretion, or the plasma volume.

3. The results of the study are compatible with the hypothesis that one or more prostaglandins contribute to maintain normotension in the rabbit and that reduction in prostaglandin biosynthesis may cause blood pressure to rise.
Carbon Dioxide Equilibration in Canine Lungs during Rebreathing and Acute Alkalosis
Authors: Latimer R. D. , Laszlo G.
Published: August 2015

1. The left lower lobe of the lungs of six anaesthetized dogs were isolated by the introduction of a bronchial cannula at thoracotomy. Catheters were introduced into the main pulmonary artery and a vein draining the isolated lobe.

2. Blood-gas pressures and pH were measured across the isolated lobe and compared with gas pressures in alveolar samples from the lobe.

3. When the isolated lobe was allowed to reach gaseous equilibrium with pulmonary arterial blood for 30 min, there was no significant difference between alveolar and pulmonary venous Pco2. Mean values of whole-blood base excess were similar in pulmonary arterial and pulmonary venous blood.

4. After injection of 20 ml of 8·4% sodium bicarbonate solution into a peripheral vein, Pco2, pH and plasma bicarbonate concentrations rose in the mixed venous blood. There was no change of whole-blood base excess across the lung, indicating that HCO−3, as distinct from dissolved CO2, did not enter lung tissue in measurable amounts.

5. No systematic alveolar—pulmonary venous Pco2 differences were demonstrated in this preparation other than those explicable by maldistribution of lobar blood flow.
Gilbert's Syndrome: Analytical Subcellular Fractionation of Liver Biopsy Specimens. Enzyme Activities, Organelle Pathology and Evidence for Subpopulations of the Syndrome
Authors: Dawson J. , Seymour C. A. , Peters T. J.
Published: August 2015

1. The hepatic organelle pathology of 12 patients with Gilbert's syndrome was studied by analytical subcellular fractionation in combination with enzymic microanalysis of liver biopsy material.

2. All patients showed increased activities of the endoplasmic reticulum marker enzyme, neutral α-glucosidase. Seven patients showed a decrease in the modal density of the endoplasmic reticulum, from 1·20 to 1·15 g/ml. These patients also showed striking hypertrophy of the hepatocyte smooth endoplasmic reticulum on electron microscopy. The remaining five patients showed normal endoplasmic reticulum density distribution with a peak at 1·20 g/ml, and had normal appearance of the endoplasmic reticulum on electron microscopy.

3. All patients showed increased activity of three lysosomal marker enzymes: N-acetyl-β-glucosaminidase, acid phosphatase and β-glucuronidase. The distribution of these enzymes in the sucrose gradients showed less enzyme in the high-density region of the gradients, indicating a reduced equilibrium density of the lysosomes. Assays of latent and sedimentable N-acetyl-β-glucosaminidase, a measure of lysosomal integrity, were normal.

4. Marker enzyme activities and density gradient distribution of other organelles, including plasma membrane (5′-nucleotidase), mitochondria (malate dehydrogenase), biliary canaliculi (γ-glutamyl transferase) and cytosol (lactate dehydrogenase) were normal. Increased catalase activities were noted.
Release of Dipeptide Hydrolase Activities from Rat Small Intestine Perfused in Vitro and in Vivo
Authors: Gardner M. L. G. , Plumb Jane A.
Published: August 2015

1. Hydrolase activities against three dipeptides were measured in mucosal cytoplasm in unperfused intestines and in mucosal cytoplasm, luminal effluents and serosal secretions after perfusion in vitro and in vivo for 1 h. Intestines in vitro were prepared both from anaesthetized rats and from freshly killed rats.

2. Only 0·6–1·9% of the initial cytoplasmic activity was recovered in the luminal effluent when intestines in vitro were prepared from anaesthetized rats. Recoveries in luminal effluents were similar (1·3–3·3%) during perfusion in vivo.

3. Losses of dipeptidases into the luminal effluent were four to eight times greater when intestines in vitro were prepared from freshly killed animals.

4. Similar losses of dipeptidases into the secretion on to the serosal surface were observed; they too were much greater when intestines were prepared from freshly killed animals.

5. Small losses of mucosal DNA during perfusion were also observed; however, losses of cytoplasmic peptidases were consistently slightly greater.

6. Enzyme loss therefore probably occurs both by sloughing of whole cells and by a more specific process which is greatly influenced by experimental procedure. Caution is necessary in the interpretation of peptide transport experiments in vitro, although the possibility that intraluminal hydrolysis is of physiological significance must not be excluded.
Muscle Protein Degradation in Premature Human Infants
Authors: Ballard F. J. , Tomas F. M. , Pope L. M. , Hendry P. G. , James B. E. , MacMahon R. A.
Published: August 2015

1. Myofibrillar protein degradation has been measured by the rate of 3-methylhistidine excretion in premature infants weighing between 635 g and 1295 g. Analyses were made in conjunction with 1–3 day nitrogen balance studies.

2. In 56 balance studies in 36 infants, total muscle protein breakdown varied between 0·70 and 2·58 (mean 1·05) g day−1 kg−1 body weight while the percentage of total muscle protein degraded each day was between 3·3 and 8·3 (mean 4·8).

3. Both total and fractional rates of protein breakdown showed highly significant negative correlations with nitrogen retention but no relationship to total energy input.

4. Protein degradation was higher than average in infants who were losing weight at the time of the balance study, lower in infants who were gaining weight and higher in those who died within 2 weeks of the analysis.

5. Myofibrillar protein breakdown was not different between infants fed orally and those receiving total parenteral nutrition.

6. Generally the effects of nitrogen and energy status on muscle protein degradation in the premature infants are different from changes reported in adult human beings or adult rats. We suggest that this difference may be a consequence of the very limited energy reserves of the premature infant.
Haemodynamic Profile of Angiotensin II Antagonism in Essential Hypertensive Patients
Authors: Hunyor S. N. , Larkin H. , Rowe Janet
Published: August 2015

1. The haemodynamic response to antagonistic (10 μg min−1 kg−1) and agonistic (40 μg min−1 kg−1) doses of saralasin was studied in young essential hypertensive patients. Blood pressure behaviour alone was thought to be inadequate to describe the response pattern.

2. Pre-saralasin setting of the renin-angiotensin axis was varied with salt intake (15 and 290 mmol of Na+/day) each for 10 days. This failed to influence blood pressure or plasma volume.

3. Antagonist blockade after low salt lowered blood pressure in three patients with the highest plasma renin values. Cardiac output rose in two of these, but it dropped in all others.

4. Decreases in cardiac output occurred with both doses of saralasin and even with suppression of the renin-angiotensin axis. This response is therefore unlikely to be due to removal of myocardial or venous angiotensin effects.

5. The renin-angiotensin system played a part in maintenance of blood pressure only with severe salt restriction and in a small proportion of cases.

6. No heart rate effect was seen with saralasin.

7. Blood pressure and total peripheral resistance responses were dependent on pre-(antagonist/ agonist) setting, but heart rate and cardiac output were not influenced by this factor.
Recordings of Renal and Splanchnic Sympathetic Nervous Activity in Normotensive and Spontaneously Hypertensive Rats
Authors: Thorén P. , Ricksten S.-E.
Published: August 2015

1. Recordings have been obtained from single sympathetic fibres to the left kidney in anaesthetized adult spontaneously hypertensive (SH) rats and Wistar—Kyoto normotensive (WK) rats.

2. Under control conditions SH rats had a mean sympathetic activity of 3·3 ± se 0·45 Hz and WK rats 1·6 ± 0·23 Hz. During noradrenaline infusion single fibre discharge decreased graudally to low levels in both SH and WK rats. The absolute decrease in fibre activity/mmHg rise of arterial pressure was greater in SH rats than in WK rats, but the reverse was true when the discharge reduction was expressed as a percentage change.

3. Recordings have also been obtained from the left splanchnic nerve in awake SH and WK rats. Upon volume load with blood, in SH rats the sympathetic activity decreased significantly more than in WK rats.

4. Thus the sympathetic discharge to the kidneys is higher in SH rats than in WK rats. Upon volume load SH rats show an exaggerated reflex response, probably due to an augmented volume-receptor response.
Absence of Sympathetic Cholinergic Vasodilatation in Cats during Early Stages of Affective Behaviour Elicited by Stimulation of Central Amygdala, Postero—Lateral Hypothalamus and Locus Coeruleus
Authors: Stock G. , Stumpf H. , Schlör K. H.
Published: August 2015

1. Stimulation of the central amygdala, posterolateral hypothalamus and locus coeruleus in cats resulted in a sustained increase in arterial pressure, an increase in heart rate, with a poststimulation bradycardia and an increase in peripheral resistance (vasoconstriction in the vessels of the hindlimbs). The behavioural pattern was characterized by an alerting reaction. Increased stimulus intensities resulted in rage reactions if the amygdala or the hypothalamus were stimulated.

2. Stimulation of the basal amygdala resulted in a cardiovascular pattern characterized by a sympathetic cholinergic vasodilatation. The concomitantly observed behaviour was characterized by alerting, anxious behaviour, eventually resulting in defence.

3. Alerting was not necessarily linked to sympathetic cholinergic vasodilatation.

4. The cardiovascular pattern including sustained vasoconstriction of the vessels of the hindlimbs was supposed to be of greater importance for the induction of hypertension than the cardiovascular pattern, including sympathetic cholinergic vasodilatation.
Low Urinary Kallikrein Excretion and Elevated Blood Pressure Normalized by Orally Applied Kallikrein in Essential Hypertension
Authors: Overlack A. , Stumpe K. O. , Ressel C. , Krück F.
Published: August 2015

1. Urinary kallikrein was measured in 67 patients with essential hypertension and 25 normotensive subjects variously on unrestricted and low sodium diet. Also, the effect of orally applied hog pancreatic kallikrein on elevated blood pressure and kallikrein excretion was evaluated.

2. Urinary kallikrein was reduced in a large subgroup of patients with sustained essential hypertension.

3. With salt restriction, urinary kallikrein rose markedly in normotensive subjects and patients with borderline hypertension but not in those with sustained hypertension.

4. Oral kallikrein normalized reduced kallikrein excretion and lowered elevated blood pressure.

5. The rise in urinary kallikrein with oral kallikrein was due to an increased formation of endogenous enzyme.

6. A defective kallikrein—kinin system may be involved in both the low urinary kallikrein excretion and the hypertension.
Blood Pressure Effects of Endogenous Brain Angiotensin in Rats are Increased by Inhibition of Prostaglandin Biosynthesis
Authors: Schölkens B. , Steinbach R. , Ganten D.
Published: August 2015

1. In Sprague—Dawley rats experiments were carried out to evaluate the influence of prostaglandins (PG) on the local generation of angiotensin (ANG) from brain angiotensinogen in cerebrospinal fluid and on the blood pressure effects of brain ANG.

2. In rats, pretreated with the PG biosynthesis inhibitor indomethacin (5 mg/kg subcutaneously every other day for 10 days), hog kidney renin was injected in doses of 0·001, 0·01 and 0·1 unit into the lateral brain ventricle.

3. At 15 min after the renin injections cerebrospinal fluid concentrations of ANG I and ANG II were markedly increased in a dose-dependent manner in the indomethacin-treated and in the untreated groups. At 60 min after the injection of renin ANG I concentrations decreased in both groups. However, the fall in ANG I in cerebrospinal fluid was more marked in indomethacin-pretreated animals.

4. Renin in doses of 0·001, 0·01 and 0·1 unit was injected into the lateral brain ventricles of unanaesthetized normotensive rats. A dose-dependent, long-lasting (> 2 h) increase in blood pressure of 9, 15 and 20% was observed. In conscious rats pretreated with indomethacin the blood pressure effects of the renin were greater (12, 23, 27%) when compared with results for untreated controls.

5. Intracerebroventricular injection into conscious rats of the ANG II antagonists [Sar1, Val5, Ala8]ANG II and [NSuc1, Val5, Phg8]ANG II in doses of 1 and 10 μg/kg reduced or abolished the renin-induced increases in blood pressure.

6. The results demonstrate that ANG I as well as ANG II are generated from brain angiotensinogen. The endogenously formed ANG II increases arterial blood pressure. This effect can be inhibited by brain intraventricular administration of specific ANG II antagonists, but it can be increased by inhibition of prostaglandin biosynthesis.
Effect of Isometric Exercise on the Renal Excretion of Sodium and Potassium in Mild Hypertension
Authors: Parfrey P. S. , Wright P. , Ledingham J. M.
Published: August 2015

1. Basal levels of pulse rate, blood pressure and rates of sodium and potassium excretion were observed in eight white male patients with mild hypertension and eight age-, sex- and colour-matched controls during an initial rest period of 90 min and then for 5 h after a 1 h period of isometric exercise involving all four limbs in rotation. The studies were repeated on another day with the subjects resting instead of exercising for 1 h.

2. Changes in systolic pressure after exercise were similar in the hypertensive and control groups, whereas the rise in diastolic pressure was higher and the rise in pulse rate lower after exercise in the hypertensive group compared with the control group.

3. The changes in the rate of salt excretion were significantly different in the two groups, the hypertensive group retaining proportionately more sodium and potassium over several hours.
Mechanism of the Haemodynamic Interaction between Atenolol, a Cardioselective β-Adrenoreceptor-Blocking Agent, and Chlorthalidone in Hypertensive Patients
Authors: Velasco M. , Guevara J. , Morillo J. , Ramírez A. , Urbina-Quintana A. , Hernández-Pieretti O.
Published: August 2015

1. The effect of the cardioselective β-adrenoreceptor antagonist atenolol on blood pressure, heart rate, systolic time interval, limb blood flow and limb vascular resistance was studied, both when the drug was used by itself, and also when combined with chlorthalidone. Plasma renin activity and plasma atenolol concentration were also measured.

2. After the administration of atenolol alone, there was a decrease in mean blood pressure from 131·8 ± sem 2·88 mmHg to 119·0 ± 4·05 mmHg (P < 0·001), in heart rate from 76·4 ± 3·58 beats/min to 57·0 ± 2·55 beats/min (P < 0·001), in calf blood flow from 9·23 ± 1·39 ml min−1100 g−1 to 5·05 ± 0·89 ml min−1 100 g−1 (P < 0·001), and an increase in calf vascular resistance from 16·54 ± 1·90 (mmHg min−1100 g−1)/ml to 28·53 ± 3·40 (mmHg min−1 100 g−1)/ml) (P < 0·005). Atenolol did not alter the pre-ejection period index significantly (P > 0·1). In atenolol-treated patients, upon addition of chlorthalidone there was a further decrease in mean blood pressure from 119·0 ± 4·05 mmHg to 105·9 ± 4·12 mmHg (P < 0·001). There was no further significant alteration in heart rate, pre-ejection period index, calf blood flow or calf vascular resistance.

3. Atenolol decreased plasma renin activity from 4·69 ± 0·87 to 2·85 ± 0·68 ng h−1 ml−1 (P < 0·05), and the addition of chlorthalidone increased it from 2·85 ± 0·68 to 3·81 ± 0·98 ng h−1 ml−1 (P < 0·05).

4. There was a 7·8 fold-interindividual variability in the relationship between plasma atenolol concentration and the dose of atenolol after a single oral dose of 100 mg of the drug.
An Evaluation of Tienilic Acid, a New Diuretic Uricosuric Agent, in the Therapy of Arterial Hypertension
Authors: Lechi A. , Covi G. , Danti G. , Riva A. Dalla , Pedrolli E. , Pomari S.
Published: August 2015

1. Tienilic acid and hydrochlorothiazide were evaluated in a double-blind trial in order to investigate their antihypertensive and metabolic effects.

2. After 5 weeks, the decreases in blood pressure and the changes in plasma or serum electrolytes, urea, creatinine, glucose, cholesterol and triglycerides, and in creatinine clearance, did not differ in the two groups of patients.

3. In patients taking tienilic acid a significant decrease in serum uric acid and an increase in urate clearance was observed, whereas in patients receiving hydrochlorothiazide a slight increase in serum uric acid, with no modification of urate clearance, occurred.

4. The diuretic and antihypertensive actions of tienilic acid and hydrochlorothiazide are very similar. The uricosuric/hypouricaemic effect of tienilic acid could assume clinical relevance in long-term therapy of hypertensive patients.
Serum Testosterone Depression Associated with Hypoxia in Respiratory Failure
Authors: Semple P. D'A. , Beastall G. H. , Watson W. S. , Hume R.
Published: August 2015

1. We have measured serum testosterone and arterial blood gas values in men with chronic obstructive airways disease.

2. Depression of serum testosterone concentrations was found.

3. The degree of testosterone depression was related to the severity of arterial hypoxia.
Creatinine Metabolism in Chronic Renal Failure
Authors: Mitch W. E. , Collier V. U. , Walser M.
Published: August 2015

1. Creatinine metabolism was studied in nine patients with severe chronic renal failure who were nevertheless in a nearly steady state with respect to their creatinine pool. Labelled creatinine was injected intravenously and the specific radioactivity of creatinine in urine was measured during the ensuing 5–7 days.

2. In each patient, the decline in specific radioactivity with time was a single exponential function after 12 h. The volume of distribution of creatinine averaged 49.1 ± 2.8% body weight. The average rate of creatinine production was 148 μmol day−1 kg−1, which is similar to predicted values for normal subjects of the same age, weight and sex. Creatinine metabolism rate/kg body weight, estimated as the difference between production rate/kg body weight, determined radioisotopically, and creatinine appearance rate (excretion plus accumulation), averaged 42 μmol day−1 kg−1.

3. Total creatinine metabolism rate/kg body weight was correlated with serum creatinine. Thus, as serum creatinine rises, an increasing fraction of the produced creatinine was metabolized rather than excreted. This relationship could account for the diminished creatinine excretion commonly seen in patients with chronic renal failure.

4. Extrarenal clearance (metabolism/serum creatinine) of this magnitude (approximately 31% of renal clearance in these patients) would be an undetectably small fraction of normal renal clearance. This could explain the absence of demonstrable creatinine metabolism in normal subjects.

5. Two pathways of metabolism were identified: a recycling of creatinine to creatine and an irreversible degradation of creatinine to products other than creatine.
Parathyroid Hormone- and Deoxycorticosterone Acetate-Induced Hypertension in the Rat
Authors: Berthelot A. , Gairard A.
Published: August 2015

1. Hypertension induced by treatment with deoxycorticosterone acetate and sodium chloride was studied in male Sprague-Dawley rats and related to parathyroid hormone secretion.

2. Lack of parathyroid hormone (due to parathyroidectomy) or decreased parathormone secretion (due to a high-calcium diet) partially inhibited the development of arterial hypertension.

3. In contrast, in thyroparathyroidectomized rats supplemented with thyroxine, the administration of parathyroid hormone rapidly elevated arterial blood pressure.

4. Maintaining a physiological concentration of serum calcium in the absence of parathyroid hormone (by feeding a high-calcium diet to parathyroidectomized rats) was not sufficient to establish mineralocorticoid hypertension.

5. These results show that parathyroid hormone is necessary for the complete development of mineralocorticoid hypertension.
Effect of Phalloidin on Biliary Lipid Secretion in Rats
Authors: Dubin Marta , Erlinger S.
Published: August 2015

1. The effect of phalloidin on bile acid, phospholipid and cholesterol secretion into bile was studied in rats with bile fistulae.

2. Phalloidin, when given for 7 days, induced a significant decrease in biliary cholesterol concentration and cholesterol saturation index. Bile acid and phospholipid concentration in bile remained unchanged. This effect was less marked in animals receiving the drug for 3 days, and not detectable in animals treated for 1 day.

3. These results provide circumstantial evidence for the hypothesis that microfilament dysfunction may lead to alterations in cholesterol secretion into bile.
Metabolic Aspects of Hypothermia in the Elderly
Authors: Stoner H. B. , Frayn K. N. , Little R. A. , Threlfall C. J. , Yates D. W. , Barton R. N. , Heath D. F.
Published: August 2015

1. Plasma concentrations of glucose, lactate, amino acids, non-esterified fatty acids, glycerol, ketone bodies, insulin and cortisol were measured in 43 elderly patients with hypothermia. In 15 of these patients forearm arteriovenous differences were also measured. Core temperatures ranged from 25.9 to 35.5°C.

2. The metabolic state was of mobilization of glycogen and triacylglycerol stores, with high plasma concentrations of lactate and lipid metabolites. The plasma concentration of glucose was raised in those with hypothermia of a short duration (<6 h). In other patients it was low in those with core temperatures around 30°C, but below this temperature it was variable and often high. Concentrations of other metabolites or hormones were not related to core temperature.

3. Plasma concentrations of cortisol were high and positively correlated with those of lactate and glycerol, suggesting active involvement in stimulation of muscle glycogenolysis and of lipolysis.

4. Plasma concentrations of insulin ranged from very low to very high and appeared to depend on the concentrations of both glucose and alanine.

5. Arteriovenous differences were generally small. There was peripheral release of lactate and of amino acids but no overall peripheral uptake of glucose. In nine out of 15 patients there was a significant peripheral release of glucose.

6. No differences in metabolism were observed between patients where the hypothermia appeared accidental and those with an obvious precipitating illness, despite a significantly lower mortality in the former group.

7. It was concluded that therapy should primarily involve rewarming of patients by physical means, without metabolic intervention.
Plasma Renin Activity in Normal Human Pregnancy and in Pregnancy-Associated Hypertension, with Reference to Cryoactivation
Authors: Gallery E. D. M. , Stokes G. S. , Györy A. Z. , Rowe J. , Williams J.
Published: August 2015

1. Because hypertension is the central feature of pre-eclampsia, and because plasma renin activity is known to be elevated in normal pregnancy (with conflicting results published for pre-eclampsia), a prospective study of plasma renin activity was conducted in pregnancy, under conditions of a fixed sodium intake, in 178 initially normotensive volunteer subjects. Thirty of these women developed pregnancy-associated hypertension (pre-eclampsia) in the third trimester.

2. There was a significant elevation of plasma renin activity from the published values for non-pregnant women, throughout gestation in normotensive women. There was no significant difference, at any stage of gestation, between the values for normal women and those who developed pregnancy-associated hypertension.

3. The extent of cryoactivation of renin, produced by usual collection procedures, was investigated in a subgroup of the total population. It was highly significant and quite variable, but was similar in those who developed pregnancy-associated hypertension and in normal pregnant women. The mean increase in plasma renin concentration in maximally cryoactivated samples was 16-fold.

4. Neither measurement of peripheral plasma renin activity nor of cryoactivatable plasma renin concentration is of value in distinguishing between normal pregnant women and those destined for, or with pregnancy-associated, hypertension.
Changes in Lung Volume, Perfusion, Ventilation and Airway Diameter in Dogs with Pulmonary Oedema
Authors: Snashall P. D. , Keyes S. J. , Morgan B. , Rawbone R. G. , McAnulty R. , Mitchell-Heggs P.
Published: August 2015

1. In dogs that were supported in the upright position and that were breathing spontaneously acute pulmonary oedema was induced either by extracellular fluid volume expansion (n = 5) or by increasing pulmonary microvascular permeability with alloxan (n = 5).

2. Before oedema was induced, the bronchi of the right lung were outlined with tantalum powder.

3. During a baseline period, standard chest radiographs were taken at inflation pressures from 0 to 2 kPa and the distributions of perfusion (with radioactive microspheres) and ventilation (with 133Xe) were measured. Arterial and mixed venous blood samples were taken to estimate the degree of venous admixture (physiological shunt) and pulmonary arterial and wedge pressures were measured.

4. After oedema had developed the radiographs and observations were repeated at a time when the pulmonary vascular pressures were insignificantly different from the baseline state.

5. With induction of oedema, particularly when due to volume expansion, the lower-lung zones decrease in volume. There were no significant changes in the upper zones.

6. Abnormal venous admixture occurred only in dogs with >20% loss of lower-zone volume; volume loss and physiological shunt were significantly correlated.

7. The distribution of perfusion changed little with induction of oedema. Volume-expanded dogs showed a slight diversion of perfusion away from the bases and towards the upper zones.

8. There was an approximately 30% reduction of ventilation to the lung bases and a corresponding increase to the upper zones.

9. With induction of oedema, bronchi were narrowed when there was a reduction of lung volume. There was a significant linear correlation between volume change and narrowing.
The Relationship between the Production of Thromboxane B2 and Malondialdehyde by Human Blood Platelets
Authors: Best L. C. , Jones P. B. B. , Russell R. G. G.
Published: August 2015

1. The formation of thromboxane B2 and malondialdehyde was studied in human platelet-rich plasma, in gel-filtered platelets and in bovine platelet microsomes.

2. Exogenous sodium arachidonate was converted into thromboxane B2 and malondialdehyde in a concentration-dependent manner. Pre-incubation of platelets with aspirin inhibited the production of both thromboxane B2 and malondialdehyde, although malondialdehyde could apparently be detected in the absence of thromboxane B2.

3. The aggregating agents, thrombin, collagen and the ionophore A23187 also caused production of thromboxane B2 and malondialdehyde. ADP and adrenaline produced a smaller rise whilst the endoperoxide analogue U 46619 had only a slight influence on thromboxane and malondialdehyde, even though they all induced aggregation.

4. Pre-incubation of platelets with imidazole or 1-N-butylimidazole, which inhibit thromboxane synthetase, resulted in an inhibition of both thromboxane B2 and malondialdehyde formation in response to collagen.

5. The results indicate that thromboxane B2 and malondialdehyde are formed in parallel, in comparable quantities. However, under the conditions used in these studies, the apparent amounts of malondialdehyde exceed those of thromboxane B2, especially in the presence of exogenous arachidonate. Thus the thiobarbiturate reaction used to assay malondialdehyde may detect other products of lipid peroxidation.

6. Platelet thromboxane B2 concentrations did not always relate to the extent of aggregation. In particular, platelet aggregation could occur in the absence of detectable thromboxane B2 production.
Conventional Haemodialysis and Ultrafiltration: Effects on Erythrocyte 2,3-Diphosphoglycerate and Oxygen Affinity in Patients with Uraemia
Authors: Severini G. , Giuliani A. , Maffi D. , Cerulli N.
Published: August 2015

1. The relationship between erythrocyte 2,3-diphosphoglycerate (2,3-DPG) and changes in blood pH and in oxygen affinity were studied in six patients treated with two dialysis techniques: conventional haemodialysis and ultrafiltration followed by conventional haemodialysis.

2. The decrease in erythrocyte 2,3-diphosphoglycerate and increase in pH after conventional haemodialysis may significantly increase the affinity of haemoglobin for oxygen and consequently result in inadequate oxygenation of tissue.

3. Ultrafiltration followed by conventional haemodialysis, on the contrary, is more beneficial for oxygenation of tissue and post-dialysis symptoms may be reduced.
The Effect of Age on the Pharmacokinetics of Diazepam
Authors: MacKlon A. F. , Barton M. , James O. , Rawlins M. D.
Published: August 2015

1. After intravenous administration to 19 subjects, aged 18–95 years, plasma diazepam concentrations were measured over 160 h. Plasma protein binding of diazepam was also measured in each subject.

2. The terminal plasma half-life of diazepam ranged from 15.0 to 125 h and was positively correlated with age (r = 0.797). Total plasma diazepam clearance was not correlated with age (r = −0.017).

3. The free fraction of diazepam ranged from 0.0137 to 0.0386 and was significantly correlated with age (r = +0.863). Free diazepam clearance, which ranged from 432 to 1870 ml/min, was also correlated with age (r = −0.717).

4. It is concluded that the increased sensitivity of the elderly to diazepam is, at least in part, due to pharmacokinetic factors.
Altered Blood Pressure and Renin Responses to Converting Enzyme Inhibition after Aprotinin-Induced Kallikrein-Kinin-System Blockade
Authors: Overlack A. , Stumpe K. O. , Kuhnert M. , Heck I.
Published: August 2015

1. The effect of aprotinin-induced blockade of the kallikrein-kinin system on haemodynamic and biochemical responses to converting enzyme inhibition by SQ 14 225 was evaluated in 26 patients with essential hypertension.

2. SQ 14 225 lowered blood pressure in high, normal and low renin hypertension. In low and normal renin patients, but not in high renin patients, the acute blood pressure-lowering effect of SQ 14 225 could be overcome by aprotinin. Aprotinin infusion produced small vasopressor effects in all groups of patients.

3. Aprotinin lowered the level of circulating active renin but not that of inactive renin.

4. It is concluded that in low and normal, but not in high, renin hypertensive patients activation of the kallikrein-kinin system is responsible for the acute blood pressure reduction observed with converting enzyme inhibition.

5. With long-term converting enzyme inhibition kallikrein-kinin system activation seems to play only a minor role.

6. The kallikrein-kinin system may be involved in the regulation of blood pressure.

7. There is no direct evidence of a participation of kallikrein in the activation of prorenin in vivo.
Role of Prostaglandin in the Antihypertensive Mechanism of Captopril in Low Renin Hypertension
Authors: Abe Keishi , Ito Toru , Sato Makito , Haruyama Toshiaki , Sato KO , Omata Ken , Hiwatari Masao , Sakurai Yutaka , Imai Yutaka , Yoshinaga Kaoru
Published: August 2015

1. The role of endogenous prostaglandins in the antihypertensive mechanism of the angiotensin converting enzyme inhibitor, captopril, was investigated.

2. An unequivocal reduction in blood pressure and significant increase in plasma renin activity and urinary prostaglandin E excretion were found after the captopril administration.

3. The changes in blood pressure, plasma renin activity and urinary prostaglandin E excretion induced by captopril were reversed after the inhibition of endogenous prostaglandin synthesis by indomethacin. However, the responses in low renin hypertension were different from those in normal renin hypertension.

4. In low renin hypertensive patients who responded to captopril, the hypotensive effect was abolished after the addition of indomethacin, whereas no marked change in blood pressure was induced by indomethacin in normal renin hypertensive patients. In contrast, plasma renin activity was markedly increased after captopril administration in normal renin hypertension, and no significant change was found in low renin hypertension.

5. Potentiation of the prostaglandin system seems to be a principal factor in the antihypertensive mechanism of captopril in low renin hypertension, and inhibition of the renin-angiotensin system is important in normal renin hypertensives.

6. The increase in renin release after the administration of captopril was inhibited by indomethacin, suggesting that an endogenous prostaglandin system may contribute to the short feedback mechanism of renin release.
Cyclic AMP Generation in Hypothalamus of Hypertension-Prone and -Resistant Rats
Authors: Kobrin I. , Ebstein R. , Ben-Ishay D.
Published: August 2015

1. The noradrenaline-induced accumulation of cyclic AMP is decreased in both the anterior and the posterior hypothalamus of hypertension-prone as compared with resistant rats, but is similar in the cortex.

2. The nonadrenaline-induced accumulation of cyclic AMP is decreased in the posterior hypothalamus as compared with the anterior hypothalamus of both strains.

3. The decreased sensitivity to phosphodiesterase inhibitor in the hypothalamus of hypertension-prone as compared with resistant rats suggests that strain differences in phosphodiesterase activity may exist.

4. Since differences in cyclic AMP were found in the hypothalamus and the medulla oblongata, regions involved in blood pressure control, but not in the cortex, they may be relevant to the diverse susceptibility to hypertension of hypertension-prone and resistant rats.
Systemic and Regional Haemodynamics in Anterior Hypothalamic Hypertension in Spontaneously Hypertensive and Wistar-Kyoto Rats
Authors: Suarez D. H. , Pegram Barbara L. , Frohlich E. D.
Published: August 2015

1. Systemic and regional haemodynamics were determined in conscious Wistar-Kyoto and spontaneously hypertensive rats with the radioactive microsphere technique after sham lesion or bilateral electrolytic lesion of the nuclei of the anterior hypothalamus.

2. Anterior hypothalamic lesions produced an increase in blood pressure, heart rate and cardiac output.

3. In the rats with lesions there were changes in regional haemodynamics: heart and skeletal muscle flow increased; renal, skin and splanchnic flow decreased.

4. The haemodynamic consequences of ablation of the anterior hypothalamus were similar in both normotensive Wistar-Kyoto and spontaneously hypertensive rats. The haemodynamic pattern resembles that seen during fighting and exercise.
Genetic Influence on Brain Catecholamines: High Brain Noradrenaline in Salt-Sensitive Rats
Authors: Iwai Junichi , Friedman R. , Tassinari Lorraine
Published: August 2015

1. Rats genetically sensitive to salt-induced hypertension showed higher levels of plasma noradrenaline and adrenaline than rats genetically resistant to hypertension.

2. The hypertension-sensitive rats had higher hypothalamic noradrenaline and lower adrenaline than resistant rats.

3. In response to a high salt diet brain-stem noradrenaline increased in sensitive rats and resistant rats exhibited a decrease on the same diet.
Pathophysiological Changes Associated with Stress-Induced Hypertension in the Borderline Hypertensive Rat
Authors: Lawlerw J. E. , Barker G. F. , Hubbard J. W. , Schaub R. G.
Published: August 2015

1. This study sought to develop an animal model which would be prone to stress-induced hypertension without spontaneously developing it.

2. Eighteen male rats, F1 offspring of spontaneously hypertensive × Wistar-Kyoto rats, had tail-cuff systolic blood pressures of 152 mmHg at 12 weeks of age. Animals were randomly assigned to three groups of six each: experimental (subjected to ‘conflict’ 2 h daily for 12 weeks), restraint control (placed in conditioning cages but not subjected to conflict) and maturation control (neither restrained nor stressed).

3. Systolic blood pressure rose significantly in experimental animals to 186 mmHg. Experimental animals studied for a 10 week follow-up period without conflict maintained the elevated pressure. In addition, these animals showed myofibrillar degeneration and an elevation in heart weight/body weight ratios. Restraint animals showed a modest elevation in pressure during the study, but not during the 10 week follow-up. Maturation animals showed no changes in blood pressure.

4. The development of a model of hypertension combining genetics with psychological stress may serve as a means for determining the factors involved in triggering and sustaining stress-induced hypertension which may prove relevant to essential hypertension in man.