bluuebunny/crossref_metadata_2025 huggingface dataset:
Impaired Autoregulatory Responses in Contralateral Kidneys of Two-Kidney, One-Clip Hypertensive Rats
Authors: Ploth D. W. , Roy R. N. , Huang Wann-Chu , Navar L. G.
Published: August 2015

1. Micropuncture and clearance experiments in two-kidney, one-clip renal vascular hypertensive rats examined the ability of the kidney contralateral to renal vascular stenosis to maintain renal function during conditions of reduced renal arterial blood pressure.

2. At their respective spontaneous blood pressures, renal vascular resistance was higher and glomerular filtration rate (GFR) and renal blood flow were not different in the contralateral kidneys of the hypertensive rats (170 ± 5 mmHg) compared with normal animals (129 ± 1 mmHg). Urine flow and absolute and fractional excretion of electrolyte were greater from the kidneys of the hypertensive animals. However, pressures in cortical structures were similar in the two groups.

3. As blood pressure was reduced acutely, the kidney contralateral to the renal artery stenosis achieved only small decreases in renal vascular resistance that failed to allow GFR, renal blood flow or pressures in cortical structures to be maintained. In contrast, normal rats efficiently autoregulated renal vascular resistance to allow GFR, renal blood flow and cortical pressures to be unchanged as blood pressure was altered between 130 and 115 mmHg. Urine flow and electrolyte excretion decreased to a greater extent in the hypertensive kidneys; at comparable blood pressure these indices of excretory function were not different in the two groups.

4. These observations indicate that the contralateral kidney can maintain normal haemodynamic and glomerular function only at elevated blood pressure and suggest the possibility that the impaired capacity to autoregulate renal resistances may contribute to the maintenance of hypertension observed in this model.
Chronic Lability of Arterial Pressure in the Rat Does Not Evolve into Hypertension
Authors: Talman W. T. , Alonso D. R. , Reis D. J.
Published: August 2015

1. In rats, electrolytic lesions of the A2 group of catecholamine neurons result in lability of arterial pressure without hypertension.

2. To establish whether labile arterial pressure, when chronic, will lead to fixed hypertension, we placed lesions in the A2 area of adult male Sprague-Dawley rats and measured mean arterial pressure, heart rate and their variability (expressed as the standard deviation) 11 months later. Controls were age-matched, unoperated or sham-operated rats.

3. In rats with A2 lesions: (a) the mean arterial pressure was lower (103 ± 7.5 mmHg; n = 6; P<0.05) than in sham-operated (123 ± 4.7 mmHg; n = 4) or unoperated (120 ± 3.1 mmHg; n = 9) controls; (b) the standard deviation of mean arterial pressure was higher (16 ± 1.8 mmHg; P<0.001) than in sham-operated (5 ± 0.7 mmHg) or unoperated controls (7 ± 0.6 mmHg); (c) the mean and standard deviation of heart rate did not differ between groups. No histopathological changes were detected in the A2 group.

4. Chronic lability of arterial pressure does not evolve into sustained hypertension nor does it induce systemic lesions.
Visualization of the Renal Arteries during Excretory Urography
Authors: Ingrisch H. , Holzgreve H. , Frey K. W.
Published: August 2015

1. Intravenous excretory urography was modified and expanded in order to visualize the aorta and the renal arteries.

2. The new procedure consists of the rapid intravenous injection of contrast medium, determination of the circulation time between the injection site and abdominal aorta, tomography with a multileaf cassette with five films (angiotomography) and continuation of the investigation as with routine excretory urography.

3. In 343 patients a total of 739 single or multiple renal arteries were identified at least partially. Of these, 83% could be clearly outlined between the aorta and the first division.

4. In 71 hypertensive patients angiography and angiotomography were separately evaluated. With angiotomography all 165 single or multiple renal arteries seen with angiography were visualized at least partially, whereas a total of 149 (90%) of renal arteries could be completely outlined between the aorta and the first division of the renal arteries.

5. A sensitivity for the presence of renal artery stenosis of 92% and a specificity for the absence of artery stenosis of 99% can be calculated for angiotomography in the diagnosis of renal artery stenosis.

6. Thus this method permits the detection or exclusion of renal artery stenosis in almost three-quarters of patients with hypertension, without angiography.
Influence of Sympatholytic Drugs on the Cardiovascular Response to Isometric Exercise
Authors: Watt S. J. , Thomas R. D. , Belfield P. W. , Goldstraw P. W. , Taylor S. H.
Published: August 2015

1. The effects of single oral doses of various sympatholytic drugs on the heart rate and blood pressure increases during isometric handgrip contraction were studied in six healthy subjects.

2. Bethanidine reduced both the systolic and diastolic increases in pressure. Clonidine reduced the systolic but not the diastolic increase. Oxprenolol alone or in combination with phentolamine or phenyoxybenzamine failed to influence the pressor response.

3. The increase in systemic blood pressure associated with sustained contraction of voluntary muscle appears to be relatively resistant to acute sympathetic adrenoreceptor blockade in man.
Cardiovascular and Autonomic Reflexes in Haemodialysis Patients
Authors: Naik R. B. , Mathias C. J. , Wilson C. A. , Reid J. L. , Warren D. J.
Published: August 2015

1. Blood pressure and heart rate responses to head-up tilt, standing, the Valsalva manoeuvre, sustained handgrip and cutaneous cold were measured in 27 haemodialysis patients (10 of whom had episodes of haemodialysis-induced hypotension) and 15 control subjects to assess autonomic nervous function. Plasma nor-adrenaline levels were measured at rest and during head-up tilt.

2. Mean resting supine blood pressure, heart rate and plasma noradrenaline levels were higher in haemodialysis patients than in the control subjects. There was no fall in blood pressure during head-up tilt or standing. The ratio of the R-R intervals of the thirtieth and the fifteenth heart beat after standing (30: 15) was lower in the patients; this may be related to their higher resting heart rate. Head-up tilt raised plasma noradrenaline levels in both groups. Heart rate responses to the Valsalva manoeuvre were similar in the patients and control subjects.

3. Systolic blood pressure and heart rate responses to sustained handgrip were similar in both groups. Diastolic and mean blood pressure changes, however, were lower in the patients. The blood pressure and heart rate responses to cutaneous cold were similar in the patients and control subjects.

4. We conclude that generalized autonomic nervous dysfunction does not appear to cause haemodialysis-induced hypotension in patients with chronic renal failure on maintenance haemodialysis.
Development of a Technique for Measuring the Oxidation Rate of a 14C-Labelled Substrate from 14CO2 Production without the Need for Collection of Expired Air
Authors: Clague M. B. , Keir M. J. , Wright P. D.
Published: August 2015

1. A method is proposed for the determination of the rate of oxidation of 14C-labelled substrates in man from blood sampling only.

2. The method was verified by simulating release of 14C into the bicarbonate pool of patients by using a constant-rate infusion of sodium [14C]bicarbonate, the plasma level of total 14CO2 (d.p.m. ml−1 70 kg−1) correlating well (r = 0.878, P = 0.001) with the infusion rate (μCi/h).

3. Techniques involved in employing this method are discussed, particularly in the light of errors involved.
Radioimmunoassay of Human Cardiac Tropomyosin in Acute Myocardial Infarction
Authors: Cummins P. , McGurk B. , Littler W. A.
Published: August 2015

1. Tropomyosin was prepared from fresh human myocardium and antisera raised in rabbits. A sensitive radioimmunoassay was developed for the detection of human cardiac tropomyosin in human sera down to levels of 1 ng/ml.

2. Values for human cardiac tropomyosin in normal patients ranged from less than 1 to 3 ng/ml. In 18 patients with acute myocardial infarction all had elevated tropomyosin levels ranging from 41 to above 200 ng/ml with a mean peak level of 101 ng/ml. In this study there were no false positive or false negative results.

3. In the initial stages of infarction the time course of appearance and peak levels of cardiac tropomyosin, total creatine kinase and creatine kinase MB isoenzyme were similar. Although total creatine kinase and creatine kinase MB isoenzyme levels were normal after 72 h in patients with single, uncomplicated infarction, cardiac tropomyosin levels were still significantly elevated above normal after this time, being 30–60% of peak values.

4. Radioimmunoassay of human cardiac tropomyosin may prove useful in the diagnosis and in the management of patients with acute myocardial infarction, particularly in the long-term postinfarction period.
Aggravation of Hypertension in Spontaneously Hypertensive Rats by Heymann Nephritis
Authors: Tikkanen I. , Miettinen A. , Fyhrquist F. , Törnroth T.
Published: August 2015

1. To explore the effect of nephritis on development of genetic hypertension we immunized 10-week-old spontaneously hypertensive rats with purified rat kidney brush-border antigen. This induces Heymann nephritis (autologous immune complex nephritis), which does not elevate blood pressure in normal rats.

2. Nephritis developed in 11 of the 12 immunized animals, and systolic blood pressure rose to a significantly higher level than in the non-immunized spontaneously hypertensive rats within 4 weeks. Blood pressure remained higher in the immunized rats at 17 weeks, heart weights were greater, but creatinine clearance remained unchanged.

3. At 6 weeks, urinary sodium excretion was greater in the immunized spontaneously hypertensive rats, whereas at 17 weeks, sodium excretion was decreased in these animals along with reduced serum protein concentration, packed cell volume and plasma renin activity, as compared with that of the controls.

4. Development of hypertension in nephritic rats, therefore, appeared unrelated to sodium excretion; signs of volume expansion emerged later.

5. Acceleration of the development of spontaneous hypertension by Heymann nephritis, also leading to sustained higher blood pressure levels than in spontaneously hypertensive rats, offers a new approach to experimental study of immune mechanisms behind acceleration of pre-existing hypertension. This may have important bearings on essential hypertension as well.
Urine Composition in Normal Subjects after Oral Ingestion of Oxalate-Rich Foods
Authors: Finch A. M. , Kasidas G. P. , Rose G. A.
Published: August 2015

1. Urinary composition was studied in nine healthy adults on unrestricted diet and low-oxalate diet with and without individual oxalate-rich foods.

2. Urine oxalate was constant on the low-oxalate and constant high-oxalate diets and only fluctuated greatly on unrestricted diet.

3. Urine oxalate was mainly due to dietary oxalate which accounts for up to two-thirds of urinary oxalate.

4. Urine oxalate was unaffected by urine volume.

5. Varying percentages of dietary oxalate were absorbed depending on the nature of the foodstuff.

6. Although tea was the main source of dietary oxalate in some people it, like strawberries, did not represent a real risk factor. Chocolates, peanuts, beetroot, rhubarb and spinach were considered as high-risk foods.

7. Calcium oxalate crystalluria at 4°C was increased significantly when the oxalate-rich foods were taken. When urine was examined at 37°C no increase in crystalluria was found.
Opposite Effects of Captopril on Angiotensin I-Converting Enzyme ‘Activity’ and ‘Concentration’; Relation between Enzyme Inhibition and Long-Term Blood Pressure Response
Authors: Boomsma F. , de Bruyn J. H. B. , Derkx F. H. M. , Schalekamp M. A. D. H.
Published: August 2015

1. The relationship between the antihypertensive action of captopril and its inhibitory effect on angiotensin I(ANG I)-converting enzyme has been investigated. Converting enzyme was measured in plasma by its ability to generate hippuric acid from the synthetic substrate hippuryl-l-histidyl-l-leucine. Inhibition by captopril appeared transient on storage of the plasma samples at −20°C, so that measurements in such samples were not a valid index of the effect in vivo.

2. Rapid reversal of captopril's inhibitory effect on ANG I-converting enzyme in plasma was achieved by the addition of N-ethylmaleimide (0.1 mmol/l). In this way an estimate of converting enzyme ‘concentration’ was obtained both in stored and in freshly prepared plasma samples. Measurements of converting enzyme ‘activity’ in freshly prepared samples, in the absence of N-ethylmaleimide, were used as an index of inhibition in vivo.

3. In eight hypertensive subjects ANG I-converting enzyme ‘concentration’ did not change after a single oral 100 mg dose of captopril. Long-term treatment of 10 hypertensive subjects with captopril was associated with a gradual increase in converting enzyme ‘concentration’ from 29 ± 2 to 47 ± 3 m-units/ml (mean ± sem) over a period of several weeks. In contrast, captopril caused a rapid fall of converting enzyme ‘activity’.

4. Abrupt withdrawal of captopril after long-term treatment caused a gradual decrease in ANG I-converting enzyme ‘concentration’ to the control value. In contrast, converting enzyme ‘activity’ rose rapidly and became equal to enzyme ‘concentration’ 2 days after the drug had been stopped.

5. The concentration of enzymatically active renin in plasma rose from 13 ± 3 to 81 ± 34 μ-units/ml during long-term captopril treatment (mean ± sem). Blood pressure fell from 168 ±4/108 ± 3 to 140 ± 3/90 ± 3 mmHg and had not returned to the control value in the first week after the drug had been stopped, despite the fact that circulating active renin and ANG I-converting enzyme ‘activity’ were elevated.

6. It is concluded that long-term inhibition of ANG I-converting enzyme by captopril is associated with an increased plasma concentration of this enzyme. The results also suggest that the level of converting enzyme ‘activity’ in plasma is not the only factor that determines the long-term effect of captopril on blood pressure.
The Contribution of Upper Airway and Inspiratory Muscle Mechanisms to the Detection of Pressure Changes at the Mouth in Normal Subjects
Authors: Gandevia S. C. , Killian K. J. , Campbell E. J. M.
Published: August 2015

1. With standard psychophysical techniques the ability of normal subjects to detect negative pressures applied at the mouth was estimated.

2. The ability to detect changes in pressure when confined to the upper airway by closure of the glottis was less than when the pressures were transmitted below the glottis and were actively overcome by inspiratory muscle contraction.

3. The ability to detect changes in pressure with the glottis open was also impaired by passive ventilation and vibration of the chest.

4. Our results imply that the most sensitive mechanism for the detection of negative pressures applied at the mouth involves afferent information from active inspiratory muscle contraction.
Postprandial Thermogenesis in Obesity
Authors: Shetty P. S. , Jung R. T. , James W. P. T. , Barrand M. A. , Callingham B. A.
Published: August 2015

1. The thermogenic response and changes in plasma substrates and hormones were tested after a liquid meal in lean, obese and formerly obese women.

2. Subjects with a family history of obesity tested either while obese or after slimming to a normal weight had a thermogenic response, which was only half that of the lean group.

3. The immediate response in plasma glucose and insulin was greater in the lean subjects, but the sustained changes in circulating substrates did not differ in the three groups. Thyroidal hormone concentrations did not alter postprandially: venous noradrenaline levels rose in the obese groups only.

4. The differences in postprandial thermogenesis at rest would reduce the energy requirements of subjects with familial obesity, but they still had a metabolic rate estimated to be nearly 1MJ (240 kcal)/day in excess of the lean group so additional thermogenic defects must exist for familial obesity to be explained solely on a metabolic basis.
Renal Prostaglandins and Water Balance: Studies in Normal Volunteer Subjects and in Patients with Central Diabetes Insipidus
Authors: Düsing R. , Herrmann R. , Glänzer K. , Vetter H. , Overlack A. , Kramer H. J.
Published: August 2015

1. In six healthy volunteer subjects polydipsic water loading significantly increased urine volume from 1203 ± 242 (sem) to 5072 ± 320 ml/24 h (P < 0.001) with a significant decrease in urinary osmolality. This increase in urine volume by more than fourfold was associated with a slight increase in urinary excretion of prostaglandin E2 from 466 ± 66 to 1017 ± 174 pmol/24 h (P = 0.05).

2. In five patients with central diabetes insipidus mean urine volume of 10 838 ± 107 ml/24 h was reduced to 1205 ± 204 ml/24 h (P < 0.001) by treatment with 1-desamino-8-arginine vasopressin (desamino-[Arg8]vasopressin; 15 μg/day) with a significant rise in urinary osmolality. Desamino-[Arg8]vasopressin treatment was associated with a significant increase of suppressed urinary excretion of prostaglandin E2 (PGE2) in four of these patients from 246 ± 66 to 2643 ± 677 pmol/24 h (P < 0.01).

3. Concomitant treatment with indomethacin in addition to desamino-[Arg8]vasopressin significantly suppressed urinary excretion of PGE2 and significantly increased urinary osmolality as compared with treatment with desamino-[Arg8]vasopressin alone.

4. Desamino-[Arg8]vasopressin significantly increased urinary excretion of adenosine 3′:5′-cyclic. monophosphate (cyclic AMP). However, there was no further change in urinary excretion of cyclic AMP during concomitant indomethacin treatment.

5. The results suggest that urine flow itself is not an important determinant of urinary PGE2 excretion. In patients with central diabetes insipidus the urinary concentrating response to desamino-[Arg8]vasopressin is enhanced during inhibition of prostaglandin synthesis without changes in urinary excretion of cyclic AMP.
Pattern of Breathing during Cigarette Smoking
Authors: Rees P. J. , Clark T. J. H.
Published: August 2015

1. Recordings were made of the pattern of breathing during and after smoking a cigarette in 14 smokers and nine non-smokers.

2. The most consistent effect was an increase in tidal volume during smoking which reverted to baseline over 1–2 min. Changes in breath times were smaller and less consistent. Similar effects were observed with intermittent inhalations of charcoal.

3. In four subjects the tidal volume response was significantly decreased by oropharyngeal and laryngeal anaesthesia with lignocaine.

4. Filtration of particulate matter from the cigarette smoke delayed the onset of changes in tidal volume.

5. The changes probably represent an irritant response with stimulation at laryngeal or oropharyngeal level.
The Excretion of Isotope in Urea and Ammonia for Estimating Protein Turnover in Man with [15N]Glycine
Authors: Fern E. B. , Garlick P. J. , McNurlan Margaret A. , Waterlow J. C.
Published: August 2015

1. Four normal adults were given [15N]-glycine in a single dose either orally or intravenously. Rates of whole-body protein turnover were estimated from the excretion of 15N in ammonia and in urea during the following 9 h. The rate derived from urea took account of the [15N]urea retained in body water.

2. In postabsorptive subjects the rates of protein synthesis given by ammonia were equal to those from urea, when the isotope was given orally, but lower when an intravenous dose was given.

3. In subjects receiving equal portions of food every 2 h rates of synthesis calculated from ammonia were much lower than those from urea whether an oral or intravenous isotope was given. Comparison of rates obtained during the post-absorptive and absorptive periods indicated regulation by food intake primarily of synthesis when measurements were made on urea, but regulation primarily of breakdown when measurements were made on ammonia.

4. These inconsistencies suggest that changes in protein metabolism might be assessed better by correlating results given by different end-products, and it is suggested that the mean value given by urea and ammonia will be useful for this purpose.
Vasopressin in the Plasma of Stroke-Prone Spontaneously Hypertensive Rats
Authors: Rascher W. , Weidmann E. , Gross F.
Published: August 2015

1. Plasma concentration of arginine vasopressin, plasma osmolality and packed cell volume were measured in stroke-prone spontaneously hypertensive rats (SHRSP) and in normotensive Wistar-Kyoto (WKY) rats at different ages.

2. In young and in adolescent SHRSP, at 6, 9 and 12 weeks of age, plasma concentration of vasopressin was diminished as compared with age-matched WKY rats (P < 0.01), whereas, in 18-week-old rats, the difference was not significant (P > 0.05). In contrast, in 24-week-old rats, plasma vasopressin was elevated as compared with WKY rats of the same age (P < 0.01).

3. In none of the age groups did plasma osmolality differ between the two strains of rats, but in all groups packed cell volume in SHRSP was higher than in WKY rats.

4. During a 48 h period of dehydration, plasma vasopressin concentrations increased similarly in SHRSP and in WKY rats of 6 and 12 weeks of age respectively.

5. It is concluded that vasopressin does not contribute to the development of high blood pressure in SHRSP rats. The reduced plasma concentration of vasopressin may account for the decreased plasma and blood volume and the slightly elevated plasma sodium concentration observed in young SHRSP rats.
Effect of Binding to Plasma Proteins on the Interpretation of Plasma Cortisol Concentrations after Accidental Injury
Authors: Barton R. N. , Passingham B. J.
Published: August 2015

1. The binding of cortisol to plasma proteins has been studied by multiple equilibrium dialysis of plasma samples taken from 14 patients before treatment after moderate or severe accidental injury and 2–5, 6–12 and 14–25 days later.

2. The total plasma cortisol concentration was initially high, but fell by 6–12 days to stable values probably near the upper limit of normal.

3. The plasma albumin and total protein concentrations fell during the first few days after the injury, but the fall in albumin was proportionally the greater. Both were rising again at the end of the study period. The albumin concentration was positively correlated with an index of its binding to cortisol calculable from the dialysis data.

4. The concentration of corticosteroid-binding globulin (CBG) rose between weeks 1 and 2 after trauma, with no statistically significant change before or afterwards.

5. The changes in binding proteins after injury were relatively small and did not greatly alter the relationship between free and total cortisol concentrations in plasma. It is concluded that in most trauma patients changes in free cortisol, generally considered to be the active fraction in plasma, can be followed adequately by measuring the total cortisol concentration.
Total Body Nitrogen and Its Relation to Body Potassium and Fat-Free Mass in Healthy Subjects
Authors: Burkinshaw L. , Morgan D. B. , Silverton N. P. , Thomas R. D.
Published: August 2015

1. The amount of lean tissue in the body can be assessed by measuring total body nitrogen, total body potassium or fat-free mass. To compare these techniques we have measured total body nitrogen, total body potassium and fat-free mass in 91 healthy subjects (62 males, 29 females).

2. Total body nitrogen in the women and civilian men agreed closely with the few values reported previously and was closely related to total body potassium and fat-free mass.

3. The simplest estimate of total body nitrogen in a subject whose body content has not been measured is the mean value for healthy people of the same sex. The standard deviation of individual values about this mean is 253 g. The precision of the estimate can be improved considerably by predicting body nitrogen from fat-free mass (156 g) and somewhat more by predicting it from body potassium (115 g). The error of measuring total body nitrogen directly is approximately 76 g.

4. When an individual's total body potassium is measured in a search for potassium depletion, the observed value must be compared with the value expected if the subject were healthy. The standard deviation of the healthy values about the group means is 408 mmol. The precision of the estimate can be improved by predicting total body potassium from fat-free mass (sd 237 mmol), and rather more by predicting it from total body nitrogen (sd 186 mmol). If gross body composition is normal, measurement of total body nitrogen has little advantage over measurement of fat-free mass by the anthropometric technique.

5. These results suggest that the simpler measure of fat-free mass from body weight and skinfold thickness has a major role in the assessment of total body nitrogen, and thus lean body tissue, in the individual.
Protection against Superoxide and Hydrogen Peroxide in Synovial Fluid from Rheumatoid Patients
Authors: Blake D. R. , Hall N. D. , Treby D. A. , Halliwell B. , Gutteridge J. M. C.
Published: August 2015

1. On exposure of synovial fluid to superoxide and hydrogen peroxide, generated enzymically or by activated polymorphonuclear leucocytes, hyaluronic acid is depolymerized and the fluid loses its lubricating properties. The ability of synovial fluid from rheumatoid patients to scavenge superoxide and hydrogen peroxide was therefore examined.

2. Synovial fluid from a range of rheumatoid patients contained no superoxide dismutase activity, insufficient caeruloplasmin to scavenge any superoxide radical and little, if any, catalase activity.

3. Total ascorbate (reduced ascorbate + dehydroascorbate) concentrations in the plasma and synovial fluid of rheumatoid patients were similar in each case. The values are at the low end of the normal range.

4. These results are discussed in relation to the role of oxygen radicals in inflammatory joint disease.
Blunted Pressor Response to Angiotensin and Sympathomimetic Amines in Bile-Duct Ligated Dogs
Authors: Finberg J. P. M. , Syrop H. A. , Better O. S.
Published: August 2015

1. The pressor and heart rate response to angiotensin II, noradrenaline, isoprenaline, tyramine and β-phenylethylamine were examined before and after bile-duct ligation in conscious trained dogs.

2. The pressor response to angiotensin II was markedly suppressed after bile-duct ligation, although responses to noradrenaline and the indirectly acting sympathomimetic amines were only slightly reduced.

3. Bradycardia, in response to the pressor drugs, and tachycardia, in response to isoprenaline, were unchanged after bile-duct ligation.

4. Refractoriness to the pressor action of angiotensin after chronic bile-duct ligation in the present study is similar to that reported previously by others in patients with liver cirrhosis.

5. No evidence was found in the bile-duct ligated dog to support a role of false neurotransmitters as mediators of the circulatory disturbances associated with liver injury.
Effect of Exercise on Protein Turnover in Man
Authors: Rennie M. J. , Edwards R. H. T. , Krywawych S. , Davies C. T. M. , Halliday D. , Waterlow J. C. , Millward D. J.
Published: August 2015

1. We have investigated the effects of moderate long-term exercise on protein turnover in fed man by measuring the extent of whole-body nitrogen production, the labelling of urinary ammonia from ingested [15N]glycine and plasma, muscle and urine free amino acid concentrations.

2. Judged both from nitrogen production, and from the extent of 13CO2 production from ingested l-[l-13C]leucine, exercise causes a substantial rise in amino acid catabolism.

3. Amino acids catabolized during exercise appear to become available through a fall in whole-body protein synthesis and a rise in whole-body protein breakdown. After exercise, protein balance becomes positive through a rise in the rate of whole-body synthesis in excess of breakdown.

4. Studies of free 3-methylhistidine in muscle, plasma and urine samples suggest that exercise decreases the fractional rate of myofibrillar protein breakdown, in contrast with the apparent rise in whole-body breakdown.
Diurnal Variation in the Intestinal Toxicity of 5-Fluorouracil in the Rat
Authors: Gardner M. L. G. , Plumb Jane A.
Published: August 2015

1. Water absorption rates by small intestine in vitro and the incidence of diarrhoea in vivo were estimated after 5-fluorouracil was injected into rats at various times of day and night.

2. Impairment of water absorption and the incidence of diarrhoea were minimal in rats on a normal dietary regimen when the 5-fluorouracil was injected at around 02.00 hours.

3. the DNA content of the mucosa of the small intestine from uninjected animals also showed a diurnal variation, with a maximum at around 03.00 hours.

4. Manipulation of the time of injections (possibly in relation to feeding time) provides a potential means for increasing the therapeutic value of 5-fluorouracil.
Haemodynamic Effects of Noise Exposure before and after β1-Selective and Non-Selective β-Adrenoceptor Blockade in Patients with Essential Hypertension
Authors: Andrén L. , Hansson L. , Björkman M.
Published: August 2015

1. Noise stimulation (100 dBA) for 10 min caused a significant increase in diastolic (7.0%, P < 0.001) and mean arterial blood pressure (4.3%, P < 0.01) in patients with essential hypertension.

2. The blood pressure response to noise was due to an increase in total peripheral resistance (4.8%, P < 0.02); heart rate, stroke volume and cardiac output were unchanged.

3. β1-selective adrenoceptor blockade (metoprolol) did not change the haemodynamic reaction pattern induced by noise.

4. Noise exposure during non-selective β-adrenoceptor blockade (propranolol) caused an accentuated blood pressure response with increments of both systolic and diastolic blood pressure as well as a more pronounced rise in total peripheral resistance.

5. The haemodynamic changes induced by noise stimulation at 100 dBA totally disappeared after 5 min of quiet rest at 40 dBA.
The Relationship between Ambulatory Blood Pressure and Echocardiographically Assessed Left Ventricular Hypertrophy
Authors: Rowlands D. B. , Ireland M. A. , Glover D. R. , McLeay R. A. B. , Stallard T. J. , Littler W. A.
Published: August 2015

1. Continuous intra-arterial ambulatory monitoring of blood pressure was recorded in 46 patients with mild to moderate hypertension under standardized conditions. M-mode echocardiography was performed after recording and left ventricular mass index calculated by standard formulae.

2. Systolic blood pressure from continuous recording was significantly correlated with left ventricular mass index (mean 24 h: r = 0.543, n = 45, P < 0.001). Diastolic blood pressure exhibited a weaker but still significant correlation with left ventricular mass index (mean 24 h: r = 0.318, n = 45, P < 0.05). Casual systolic blood pressure was significantly correlated with left ventricular mass index (r = 0.476, n = 46, P < 0.001) but casual diastolic blood pressure did not correlate with left ventricular mass index (r = 0.245, n = 46). Awake blood pressure variability, age, resting plasma renin activity and resting plasma noradranaline levels did not have a significant correlation with left ventricular mass index.

3. Nine patients were treated for 16 weeks with once-daily timolol and repeat ambulatory monitoring and M-mode echocardiography was performed with the same protocol.

4. Once-daily timolol provided good 24 h control of blood pressure and repeat echocardiography showed a reduction in left ventricular mass index in that group of patients (t = 2.59, P < 0.05).
Combined Pre- and after-Load Reduction in Hypertensive Patients with Cardiomegaly and Normal Filling Pressure
Authors: Hunyor S. N. , Nelson G. I. , Donnelly G. L.
Published: August 2015

1. Twelve hypertensive patients with cardiomegaly were treated with equivalent antihypertensive doses of prazosin (11 weeks) and β-adrenoceptor-blocking drug (9 weeks) in random crossover fashion.

2. At the end of each treatment period haemodynamic assessment included the response to isometric handgrip exercise (4 min at 30% of maximum voluntary contraction).

3. Resting cardiac index and heart rate were higher on prasozin although the latter was only 65 beats/min. Systemic vascular resistance and left ventricular filling pressure were insignificantly higher on β-adrenoceptor-blocking drug.

4. During isometric handgrip the blood pressure rise was similar on the two regimens, but the mechanism whereby it was achieved was quite different. On prazosin an increase in cardiac output accounted for the pressor response with virtually no change in systemic vascular resistance, whereas on β blockade there was a flat cardiac output response with a marked increase in the systemic vascular resistance.

5. Ventricular function curves indicated a predominant utilization of the Frank-Starling mechanism during β blockade, whereas enhanced contractility played a major role during prazosin treatment.

6. The isometric exercise response pattern during prazosin treatment resembles that in normal subjects whereas in the β blockade phase it corresponded to that in untreated hypertensive patients with left ventricular hypertrophy or cardiomegaly or to that in congestive heart failure patients.

7. There was no evidence of harmful effects of combined pre- and after-load reduction in hypertensive patients with cardiomegaly and normal filling pressure, even under conditions of moderately severe cardiac loading with isometric exercise.
Excitatory Effect of Converting Enzyme Inhibitors on Efferent Sympathetic Postganglionic Nerve Activity to the Kidney in the Rat
Authors: Recordati G. , Genovesi S. , Cerati D. , Di Cintio R. , Gerometta P.
Published: August 2015

1. Experiments were designed to evaluate the effect of converting enzyme inhibitors on autonomic nervous system function in the rat.

2. Arterial blood pressure, heart rate, efferent postganglionic sympathetic activity and afferent nerve activity from the right renal nerves were recorded in anaesthetized, spontaneously breathing, non diuretic rats, either with an intact spinal cord or with a spinal cord transected at the T6 level, before, during and after intravenous injections of 0.5–1.0 mg/kg of teprotide or captopril.

3. After injection of drugs, efferent sympathetic nerve activity markedly increased and reached its peak value 4 min later, both in rats with an intact spinal cord (101 ± 21% mean ± se, above the control discharge) and with a spinal cord transected at the T6 level (166 ± 41%, above the control).

4. Afferent activity from the renal nerve, on the other hand, did not consistently change during converting enzyme blockade.

5. The results indicate that the efferent sympathetic excitation cannot be due either to a baroreceptor or to a renorenal reflex. This excitation might be responsible, at least in part, for the increase in renin secretion which follows the blockade of angiotensin-converting enzyme.
Exaggerated Fractional Sodium Excretion in Hypertension with Advanced Renal Disease: The Role of Renal Prostaglandin and Kallikrein
Authors: Abe Keishi , Imai Yutaka , Sato Makito , Haruyama Toshiaki , Sato KO , Hiwatari Masao , Kasai Yutaka , Itoh Sadayoshi , Yasujima Minoru , Seino Masahide , Yoshinaga Kaoru
Published: August 2015

1. The role of renal prostaglandin E (PGE) and kallikrein in the mechanism of the exaggerated fractional sodium excretion in hypertensive patients with advanced renal disease was investigated.

2. Urinary excretion of PGE and kallikrein was significantly decreased in patients with sustained hypertension.

3. Four times higher values for fractional sodium excretion and four or five times higher values for the urinary excretion of PGE corrected for creatinine clearance were found in patients with sustained hypertension. There was a significant positive correlation (r = 0.677) between the two, suggesting that PGE in the renal tubular compartment may be involved in the mechanism of the exaggerated fractional Na excretion in patients with advanced renal disease.

4. The urinary excretion rate of kallikrein corrected for creatinine clearance was three times greater in patients with borderline hypertension, but not significantly increased in those with sustained hypertension, compared with that in healthy volunteers.
An Analysis of the Blood Pressure Response to Labetalol in Hypertensive Patients
Authors: McNeil J. J. , Anderson A. E. , Louis W. J.
Published: August 2015

1. Blood pressure measurements were made in hypertensive subjects after single intravenous and oral doses of labetalol and subsequently during chronic administration.

2. Oral therapy can be as effective as intravenous therapy in achieving acute blood pressure reduction.

3. Blood pressure control with chronic labetalol monotherapy was satisfactory in 11 of the 12 subjects.

4. High dose therapy with labetalol and 49 diuretic produced greater postural blood pressure falls.
Antihypertensive Effect of Guanfacine: Long-Term ‘Once-a-Day’ Treatment and Sudden Withdrawal
Authors: Szám I. , Holló J.
Published: August 2015

1. Twenty patients with essential hypertension were treated with guanfacine given in single daily doses of 1–5 mg over a period of 24 weeks. Compared with the initial values at the end of the first wash-out period, there was a significant decrease of blood pressure and heart rate. The most common side effect, dryness of the mouth, usually disappeared after 8–10 weeks of treatment. No changes in laboratory values were seen. In the post-treatment placebo period there were significant increases in blood pressure and heart rate compared with the last readings during the treatment period. However, these never exceeded the pretreatment values.

2. In a second trial guanfacine (1–5 mg daily) was abruptly discontinued in 11 patients after 6–20 weeks' treatment. Blood pressure was measured twice a day, in lying and standing positions, during the 4 days before abrupt withdrawal of guanfacine and for 7 days after discontinuation. Clopamide was given concurrently to two patients, and this was continued after withdrawal of guanfacine. Only in two patients did the blood pressure rise to values above the initial levels (30 mmHg systolic and 10 mmHg diastolic), but no clinical symptoms were observed during the withdrawal. A transitory increase of heart rate of between 10 and 30 beats/min was observed in five patients after abrupt discontinuation of the drug.
Autonomic Control of the Immediate Heart Rate Response to Lying Down
Authors: Bellavere F. , Ewing D. J.
Published: August 2015

1. The initial heart rate response to lying down was analysed in 18 younger (23–36 years) and 10 older (48–67 years) normal subjects, and consisted of an immediate shortening of the R—R interval reaching a maximum around the third or fourth beat after lying, followed by a lengthening beyond the resting value to reach a steady level around beats 25–30. In six diabetic patients with autonomic neuropathy, no cardiac acceleration occurred and the deceleration was markedly diminished.

2. In eight young normal subjects the pattern of response was altered by atropine, which abolished the initial shortening of the R—R interval over the first 10 beats. Thereafter slow but steady lengthening of the R—R interval occurred. With additional propranolol the later part of the response was further attenuated. Propranolol alone did not affect the normal pattern of response.

3. Six young normal subjects performed short periods of muscular exercise, lying, sitting and standing, and the heart rate patterns were compared with that after lying down. After both manoeuvres R—R interval shortened and then lengthened back to the resting level within 10–15 beats. Thereafter it remained steady after muscular exercise, but continued to lengthen after lying down.

4. In four young normal subjects, no initial R—R interval shortening occurred during fast or slow ‘passive’ tilting from the 80° head-up position to horizontal, whereas shortening was seen both with fast and slow ‘active’ lying down.

5. It is concluded that the immediate part of the heart rate response to lying down (during the first 10 beats) is under vagal control and the later part predominantly under sympathetic control. The first part of the response is probably due to a ‘muscle—heart’ reflex which occurs during the change in posture.
Muscarinic Acetycholine Receptors of the Small Intestine and Pancreas of the Rat: Distribution and the Effect of Vagotomy
Authors: Isaacs P. E. T. , Whitehead J. S. , Kim Y. S.
Published: August 2015

1. The distribution of muscarinic cholinergic receptors (mAChR), detected by atropine-inhibitable binding of [3H]quinuclidinyl benzilate, was examined in membrane fractions of pancreas, small intestinal muscle, mucosa, villi and crypts of sham-operated and vagotomized rats.

2. Specific (atropine inhibitable) [3H]quinuclidinyl benzilate binding was greater to the ileal mucosa than to jejunal mucosa or to duodenal mucosa, but binding to crypt and villus fractions was not significantly different. This distribution of specific [3H]quinuclidinyl benzilate binding suggests that cholinergic mucosal innervation is more important in the ileum than the jejunum.

3. Vagotomy produced a decrease in the amount of specific [3H]quinuclidinyl benzilate binding to duodenal mucosa only, suggesting that parasympathetic denervation of the small intestine does not cause mucosal hypersensitivity to acetylcholine by an increase in mAChR.
Glucocorticoids Decrease the Conversion of Thyroxine into 3,5,3′-Tri-Iodothyronine by Isolated Rat Renal Tubules
Authors: Heyma P. , Larkins R. G.
Published: August 2015

1. The effect of glucocorticoids on the deiodination of thyroxine (T4) to 3,5,3′-tri-iodothyronine (T3) was studied in rat renal tubules prepared by collagenase digestion.

2. In short-term (6 h) experiments, cortisol and dexamethasone inhibited the conversion of T4 into T3 at concentrations of 2 × 10-4 mol/l and 2 × 10-5 mol/l respectively. The inhibition by cortisol and dexamethasone was time dependent and was prevented by actinomycin D and progesterone, suggesting that the inhibition is mediated by an effect on nuclear transcription dependent on binding to glucocorticoid receptors.

3. In long-term (16 h) experiments, cortisol and dexamethasone inhibited T4 to T3 conversion by the tubules at concentrations of 1 × 10-12 mol/l and above. In addition, physiological concentrations of corticosterone (1 × 10-8 mol/l) were able to decrease T3 generation from T4.

4. Our data provide strong evidence that physiological concentrations of glucocorticoids are able to affect T3 production from T4 directly and suggest that they may be important regulators of T4 deiodination.
Effect of Vagotomy on the Breathing Pattern and Exercise Ability in Emphysematous Patients
Authors: Bradley G. W. , Hale T. , Pimble J. , Rowlandson R. , Noble M. I. M.
Published: August 2015

1. The potential value of right vagotomy for the relief of breathlessness has been explored in five patients with emphysema. Two patients had symptomatic improvement, two had minor symptomatic improvement, and one was unchanged.

2. Exercise ventilation was not noticeably depressed by unilateral right vagotomy in the two patients investigated fully, but the pattern of breathing was altered. After vagotomy, breathing was deeper, and the rise in the frequency of breathing with exercise was depressed.

3. After right vagotomy the response to rebreathing carbon dioxide also consisted of slower deeper breaths.

4. Right vagotomy sometimes appears to remove an influence preventing slow deep breathing and exacerbating dyspnoea.

5. Results of bilateral pulmonary denervation, attempted in one patient, were complicated by the need for left thoracotomy, which removed any possible beneficial effects.
Sources of Bile Pigment Overproduction in Gilbert's Syndrome: Studies with Non-Radioactive Bilirubin Kinetics and with δ-[3,5-3H]Aminolaevulinic Acid and [2-14C]Glycine
Authors: Zeneroli M. L. , Piaggi V. , Cremonini C. , Gozzi C. , Ventura E.
Published: August 2015

1. The kinetics of non-radioactive bilirubin were investigated in 100 patients with chronic non-haemolytic unconjugated hyperbilirubinaemia and in nine normal volunteers.

2. The patients with Gilbert's syndrome were divided on the basis of a two-compartment model into two distinct groups: group 1 (74 patients) with decreased hepatic uptake and conjugation of bilirubin and a bilirubin turnover rate within the normal range, and group 2 (26 patients) having normal uptake, impaired conjugation and increased bilirubin turnover rate.

3. On the basis of these findings, studies were made of early pigment production in four patients of group 1, in six patients of group 2 and in four of the normal volunteers, with [14C]glycine and ş-[3H]aminolaevulinic acid.

4. After receiving injections of labelled haem precursors, the four patients in group 1 had a normal rate of incorporation of both tracers, whereas abnormalities in incorporation were found in group 2. Four patients showed an increase of the first component of the early peak of [14C]bilirubin as well as of the early peak of [3H]bilirubin, suggesting an increased turnover of hepatic haem. Two patients showed an increased incorporation of [14C]glycine characterized by the fusion of the two early peaks, whereas the incorporation of the δ-[3H]aminolaevulinic acid was normal, indicating the presence of a primary shunt hyperbilirubinaemia.

5. The results confirm that Gilbert's syndrome is a heterogeneous condition with respect to bilirubin turnover rate. The population of Gilbert's syndrome with increased bilirubin turnover rate comprises not only patients with an increased haem erythroid turnover, but also patients with increased metabolism of nonerythroid haem protein in the liver.
Preservation of the Hypoxic Drive to Breathing in Diabetic Autonomic Neuropathy
Authors: Calverley P. M. A. , Ewing D. J. , Campbell I. W. , Wraith P. K. , Brash H. M. , Clarke B. F. , Flenley D. C.
Published: August 2015

1. Unexplained cardiorespiratory arrests have been reported in patients with diabetic autonomic neuropathy and these could be due to denervation of the carotid chemoreceptors.

2. We have studied the ventilatory response to transient hypoxia () during exercise in 22 male diabetic patients, six with symptomatic and cardiovascular evidence to suggest diabetic autonomic neuropathy (DAN+) and 12 without these features (DAN−).

3. There was no difference in the ventilatory response to transient hypoxia between the different groups of diabetic patients ( in DAN+ patients = −0·9 ± 0·2 litre min−1 kPa−1; in DAN− patients = −1·2 ± 0·6 litres min−1 kPa−1) even allowing for differences in the level of exercise achieved (CO2 production in DAN+ patients = 743 ± 103 ml/min; CO2 production in DAN– patients = 800 ± 144 ml/min). These results fell within our normal range for ventilatory response to transient hypoxia at this level of exercise.

4. The heart rate response to transient hypoxia varied within the groups but was significantly (P < 0·05) less in the patients with established diabetic autonomic neuropathy.

5. We conclude that the peripheral chemoreceptors are intact in diabetic autonomic neuropathy and that other mechanisms must be implicated in the unexpected cardiorespiratory arrests seen in these patients.