bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma levels of an endogenous Na+–K+ pump inhibitor in relation to haemodynamic data in cardiopathic patients
Authors: Delva Pietro , Devynck Marie-Aude , Degan Maurizio , Pernollet Marie-Gabrielle , Carraroli Marco , Capra Claudio , Steele Anthony , Lechi Alessandro
Published: August 2015

1. Despite the fact that numerous studies provide evidence for the existence of an endogenous inhibitor of the cell membrane Na+-K+ pump in plasma, little is known about the relationships between this factor and the main haemodynamic parameters.

2. In order to shed some light on this, we attempted to correlate haemodynamic parameters, measured during heart catheterization in a group of 22 cardiopathic subjects, with plasma digitalis-like activity levels, determined by two different procedures.

3. The ability of plasma to inhibit a human renal Na+-K+-ATPase showed an inverse correlation with cardiac index and a direct correlation with peripheral resistance. Plasma cross-reactivity with digoxin antibodies correlated directly with left atrial pressure.

4. These results furnish confirmation of a number of theoretical assumptions which attribute to the digitalis-like factor the ability to modify the contractility of the cardiovascular system.
Circulatory adaptation to orthostatic stress in healthy 10–14-year-old children investigated in a general practice
Authors: Dambrink J. H. A. , Imholz B. P. M. , Karemaker J. M. , Wieling W.
Published: August 2015

1. The magnitude and time course of circulatory adaptation to active standing were investigated in healthy premenarchic girls and boys (n = 24; 10–14 years old) by non-invasive measurement of heart rate and continuous finger blood pressure (Finapres).

2. Four subjects (two girls, two boys) showed presyncopal symptoms after 4–9 min of free standing.

3. In the 20 non-fainting subjects, changes in blood pressure and heart rate upon standing did not differ between girls (n = 10) and boys (n = 10). In the initial phase of standing (first 30 s) systolic and diastolic blood pressures dropped by 22 ± 14 (mean ± sd) and 16 ± 7 mmHg, respectively, at 8 ± 2 s. Blood pressure subsequently recovered and showed an overshoot in all subjects. The transient drop in blood pressure was accompanied by an increase in heart rate of 40 ± 7 beats/min. These characteristic transient changes were not observed with passive head-up tilt. During the early steady-state phase (2 min), systolic blood pressure was similar to the supine value and diastolic blood pressure rose by 11 ± 5 mmHg. Heart rate increased by 25 ± 11 beats/min. In six of the subjects (three girls, three boys) the increase in heart rate exceeded 30 beats/min (postural tachycardia). Little further changes were observed during prolonged (10 min) standing.

4. Typical findings in the four near-fainting subjects were higher supine heart rates, no blood pressure overshoot in the initial phase (in three out of four subjects), postural tachycardia in the early steady-state phase and progressive decreases in blood pressure and heart rate afterwards.

5. In conclusion, for investigation of orthostatic circulatory adaptation in childhood it is important to pay attention to the dynamics of the circulatory response. No important differences appear to exist in orthostatic circulatory control between premenarchic girls and boys: orthostatic tachycardia and fainting appear to be common in both.
Mast cell tryptase and histamine concentrations in bronchoalveolar lavage fluid from patients with interstitial lung disease
Authors: Walls A. F. , Bennett A. R. , Godfrey R. C. , Holgate S. T. , Church M. K.
Published: August 2015

1. Mast cell activation in the lung was investigated by measuring concentrations of mast cell tryptase and histamine in the bronchoalveolar lavage fluid from patients with bronchial carcinoma, sarcoidosis, extrinsic allergic alveolitis or cryptogenic fibrosing alveolitis and from normal subjects.

2. Histamine concentrations in bronchoalveolar lavage fluid supernatants were elevated in the bronchial carcinoma and cryptogenic fibrosing alveolitis groups, and were correlated with the histamine content of the cells recovered.

3. An avidin-biotin-enhanced antigen-capture e.l.i.s.a., using polyclonal rabbit antibody specific for tryptase, and mouse monoclonal antibody AA5, allowed the quantification of tryptase in all samples of bronchoalveolar lavage fluid. Tryptase concentrations were increased in the bronchial carcinoma and extrinsic allergic alveolitis groups and in some of the patients with sarcoidosis, and the levels correlated with mast cell numbers and also with concentrations of albumin.

4. There was no significant correlation between levels of tryptase and histamine, suggesting differences in the rates of metabolism or different cellular sources.

5. The tryptase and histamine concentrations measured suggest that there is continuous degranulation of mast cells within the normal lung, but that this process is more pronounced in patients with bronchial carcinoma or interstitial lung disease.
Local blood volume changes in women with pelvic congestion measured by applied potential tomography
Authors: Thomas D. Clive , McArdle Frank J. , Rogers Vera E. , Beard Richard W. , Brown Brian H.
Published: August 2015

1. Applied potential tomography is a new, noninvasive technology for observing changes in blood volume. We have used it to study 12 women with lower abdominal pain caused by pelvic congestion, and 15 control subjects.

2. A significant increase in blood volume of 1.8% was observed in the pelvis of women with congestion when changing from the supine to the erect position, and of 2.7% in the control subjects (P< 0.0002). The difference between the groups was not significant.

3. The distribution of the area over which blood volume changes took place was significantly different between the two groups (P< 0.002). More of the posterolateral part of the pelvis was involved in women with pelvic congestion than in the control subjects.

4. Applied potential tomography distinguishes between normal women and those having pelvic congestion with a specificity of 87% and a sensitivity of 75%.
Hepatic energy status in hypotension of different aetiologies in dogs
Authors: Yokoyama Tadashi , Okamoto Ryoji , Yamamoto Yuzo , Manaka Dai , Sasaki Hirokazu , Washida Masanobu , Kitai Toshiyuki , Tanaka Akira , Yamaoka Yoshio , Kumada Kaoru , Ozawa Kazue
Published: August 2015

1. The alterations in hepatic energy metabolism in hypotension induced by the administration of trimetaphan camsylate (Arfonad) were investigated in comparison with those produced by hypotension resulting from massive haemorrhage by measuring the arterial ketone body ratio, which reflects the hepatic mitochondrial redox state, and other indices of hepatic energy metabolism together with simultaneous measurement of hepatic blood flow in dogs.

2. Mean arterial blood pressure was decreased from 130 mmHg to 60 mmHg by the continuous intravenous infusion of trimetaphan camsylate or by the use of Wiggers' shock model. In hypotension induced by trimetaphan camsylate, the arterial ketone body ratio, ATP and total adenine nucleotide concentrations and energy charge were maintained at near-control values throughout the experimental period. By contrast, the arterial ketone body ratio decreased from 1.04 ±0.09 to 0.29 ±0.06 at 3 h after haemorrhage in Wiggers' shock model (P <0.01). The ATP and total adenine nucleotide concentrations and energy charge also decreased significantly in this model (P <0.05). The difference in hepatic energy status was also shown by data from 31P nuclear magnetic resonance spectroscopy.

3. During hypotension, portal venous and total hepatic blood flows diminished significantly compared with the control values in each group (P <0.01). Although there was no significant difference in total hepatic flow between the two groups, the portal venous blood flow in hypotension induced by trimetaphan camsylate was significantly higher than that in Wiggers' shock model (P <0.05).

4. During hypotension induced by trimetaphan camsylate, the hepatic energy metabolism was well maintained at the mean arterial blood pressure value of 60 mmHg, but in haemorrhagic hypotension it was severely curtailed, although there was no significant difference in total hepatic blood flow between the two groups. It is conjectured that the portal venous blood flow contributes significantly to the maintenance of hepatic energy metabolism and hepatic tissue perfusion during hypotension induced by trimetaphan camsylate.
Intrathoracic airstream temperatures during acute expansions of thoracic blood volume
Authors: Gilbert Ileen A. , Regnard Jacques , Lenner K. A. , Nelson J. A. , McFadden E. R.
Published: August 2015

1. To determine the validity of employing intrathoracic heat flux as a reflection of changes in bronchial blood flow, we used a thermal probe to record airstream temperatures within the tracheobronchial tree in five normal and five asthmatic subjects during isocapnic hyperventilation challenges with and without inflation of the lower limb bladders of a pressure suit.

2. During hyperpnoea, airstream temperatures fell progressively in both subject groups. When blood volume was acutely shifted from the legs into the thorax via antishock trousers, airstream temperatures within the tracheobronchial tree rose and were significantly higher than the temperatures recorded during hyperpnoea alone. In the normal subjects, once hyperpnoea ceased, the rate of airway re-warming was similar whether or not the antishock trousers were inflated. In the asthmatic subjects, however, shifting blood into the thorax attenuated the obstructive response to hyperpnoea and slowed the rate of re-warming.

3. These data demonstrate that changes in airway blood volume are reflected in fluctuations in intrathoracic heat exchange and that disruption of the end hyperpnoea thermal gradient attenuates the airway obstruction that follows hyperpnoea. Since the bronchial blood supply is the major source of heat to the airways, this circulation may play an important role in thermally induced asthma.
Effect of different levels of briefly sustained ventricular pressure on arrhythmia in the isolated working rat heart
Authors: James M. A. , Jones J. V.
Published: August 2015

1. The effect of different levels of ventricular pressure upon the prevalence of ventricular arrhythmias has been studied in 42 rat hearts by using the isolated working heart model.

2. The results have shown that there is an increased prevalence of arrhythmia at the highest levels of pressure tested in hearts from both normal and hypertensive rats. In hearts from normal rats total ectopic counts were 304 at 140 mmHg and 150 at 60 mmHg (P < 0.05). In hearts from hypertensive rats total ectopic counts were 4217 at 180 mmHg and 2179 at 100 mmHg (P < 0.05).

3. Hearts from hypertensive rats demonstrated significantly more ectopic activity than hearts from normal rats at all test pressures. Median values for ectopic counts for each study period were 68 in hearts from hypertensive rats and seven in hearts from normotensive rats (P < 0.001).

4. There was evidence that the increased arrhythmia observed was not due to ischaemia or fatigue, and it seems likely that these effects of raised pressure are due to its effect on ventricular wall stress. The differences between various pressures were relatively small, but do suggest that a sustained increase in ventricular wall stress is arrhythmogenic.

5. This small arrhythmogenic effect over the relatively short period of these studies may be of much greater significance when considered in the context of the prolonged periods for which the diseased heart may be subjected to raised wall stress.
Arginine vasopressin attenuates phenylephrine-induced forearm vasoconstriction in men
Authors: Harada Seiki , Imaizumi Tsutomu , Momohara Michiko , Masaki Hiroyuki , Ando Shin-Ichi , Takeshita Akira
Published: August 2015

1. The aim of this study was to examine whether arginine vasopressin modulates the vasoconstricting action of phenylephrine in human forearms.

2. In seven healthy subjects, we determined the percentage increases in forearm vascular resistance evoked by intra-arterial infusion of phenylephrine at graded doses during simultaneous intra-arterial infusion of saline or arginine vasopressin at two doses. Similarly, in another seven subjects, we examined the effects of intra-arterial infusions of saline or angiotensin II on the vasoconstricting action of intra-arterial phenylephrine.

3. Arginine vasopressin and angiotensin II caused small, but insignificant, increases in baseline forearm vascular resistance. Arginine vasopressin at the two doses significantly attenuated the percentage increases in forearm vascular resistance evoked with phenylephrine at graded doses. Angiotensin II did not alter the forearm vascular responses to phenylephrine.

4. Intra-arterial infusion of arginine vasopressin at doses of 0.6 and 1.8 ng/min raised the plasma arginine vasopressin concentration in the venous effluents from 1.6 ± 0.3 (control) to 4.0 ± 0.9 and to 16.4 ± 6.9 pg/ml, respectively.

5. These results suggest that arginine vasopressin at physiological concentrations with a minimal direct effect on resistance arteries attenuates the vasoconstricting action of phenylephrine in human forearms.
Metabolic balance studies of mineral supplementation in osteoporosis
Authors: Stamp Trevor , Katakity Monica , Goldstein A. J. , Jenkins M. V. , Kelsey C. R. , Rose G. A.
Published: August 2015

1. We studied the effect of mineral supplementation and its duration is osteoporosis by analysing the calcium and phosphorus balances of 49 treated osteoporotic patients whose median length of calcium treatment was 19 weeks with a range of 8 days to over 4 years. Forty-four studies satisfied statistical criteria of reproducibility and included 35 women (10 also receiving oestrogen replacement therapy) and nine men.

2. Mean calcium balance was positive in women taking calcium supplements alone, +1.9 ± 2.5 mmol daily (P < 0.002), and was significantly more positive (P < 0.05) in women also taking oestrogens, +4.2 ± 2.1 mmol daily. Calcium balance was not significantly positive in men.

3. Calcium balance correlated negatively with duration of supplementation, but, significantly, only when duration of supplementation was expressed logarithmically (r = −0.401, P < 0.01) giving the regression equation y = 4.2–1.6 log x, where y = calcium balance in mol/day and x = duration of supplementation in weeks. Theoretical net calcium retention, without allowance for dermal loss, could be calculated by integration.

4. Mean phosphorus balance was significantly positive in both groups of women and in the whole population. Although its correlation with duration of supplementation did not reach statistical significance (P < 0.1), the ratio of the regression slopes for calcium and phosphorus, 1.5:1, corresponded to their molar ratio in bone.

5. These statistics are, we believe, the first to describe an exponential decline in calcium balance during mineral treatment of osteoporosis, but they firmly suggest that such treatment, with or without oestrogen therapy, conveys temporary benefit.
Effect of induced supraventricular tachycardias on changes in urine output and plasma hormone levels in man
Authors: Kaye Gerald C. , Bayliss Peter , Lowry Philip J. , Drury P. L. , Camm A. John
Published: August 2015

1. A symptomatic diuresis, polyuria, sometimes accompanies paroxysmal tachycardias in man. A study was undertaken in patients with inducible supraventricular tachycardia, irrespective of the symptom of polyuria, to measure simultaneous changes in urine output and plasma hormone levels during the arrhythmia.

2. During 14 episodes of induced tachycardia in 10 patients, there was a significant increase in mean urine flow, which was independent of the state of patient hydration. During a mean tachycardia duration of 30 ± 3 min, the mean group urine flow increased from 3.2 ± 2.3 ml/min to 7.6 ± 3.7 ml/min (P<0.001). This was characterized by a consistent increase in free water excretion and a variable increase in sodium excretion.

3. The plasma atrial natriuretic peptide level (five patients) significantly increased from 7.6 ± 4.6 pg/ml to 34.6 ± 21.7 pg/ml (P<0.02) during the arrhythmia. There was no significant change in the plasma argininevasopressin level and a non-significant reduction in plasma renin activity.

4. This study has shown that induced supraventricular tachycardias in man are accompanied by a significant diuresis. The mechanisms responsible remain unknown, but do not appear to involve the plasma arginine-vaso-pressin level alone.
A comparison of the pharmacological and mechanical properties in vitro of large and small pulmonary arteries of the rat
Authors: Leach R. M. , Twort C. H. C. , Cameron I. R. , Ward J. P. T.
Published: August 2015

1. The mechanical and pharmacological properties of small pulmonary arteries (100–300 μm normalized lumen diameter) were directly compared with those of the left main pulmonary artery (1–2 mm) from the rat. The active and passive length-tension characteristics and responses to a variety of agonists and antagonists were dependent on arterial diameter.

2. Maximum contractile function was obtained in both groups of vessels when stretched so as to give an equivalent transmural pressure of 30 mmHg. This is substantially lower than that found for systemic vessels, and reflects the normal low pulmonary arterial pressure.

3. Noradrenaline was a powerful vasoconstrictor in large but not small pulmonary arteries (P> 0.001). In contrast, bradykinin produced a significantly greater response in the small arteries (P < 0.001). In comparison with large pulmonary arteries, small arteries were more sensitive to noradrenaline (P<0.05) and 5-hydroxytryptamine (P < 0.001), less sensitive to endothelin-1 (P> 0.001) and had the same sensitivity to prostaglandin F2α.

4. The mechanism that maintains the low arterial tone of the pulmonary circulation is unknown, but it may involve the release of relaxing factors from the endothelium. In this preparation, basal resting tone could not be demonstrated in either large or small arteries.

5. Acetylcholine-induced relaxation of pre-contracted pulmonary arteries was reduced or absent in the small artery, despite histological evidence of an intact endothelium. In large arteries pre-contracted with prostaglandin F2α, acetylcholine (100 μmol/l) caused 88.2% relaxation compared with 25.2% in the small artery.

6. These results suggest that it would be unwise to extrapolate from results obtained either in large pulmonary artery preparations or in perfused lungs to what may occur in the functionally important resistance arteries.
Pressor response to a postural change in cirrhosis: an experimental study in the CCI4-treated rat
Authors: Bomzon Arieh , Weinbroum Avraham , Blendis Laurence M.
Published: August 2015

1. Systemic hypotension, blunted cardiovascular responsiveness to noradrenaline and an abnormal hypertensive pressor response to a postural change have been described in cirrhotic patients.

2. We have examined the role of blunted responsiveness in these abnormalities by studying basal arterial blood pressure and its response to a postural change (vertical head-up 90° tilting) in conscious and pithed CCl4-treated (cirrhotic) rats, as well as assessing the pressor response to noradrenaline in vivo and the vascular contractile response to noradrenaline in vitro.

3. A diminished hypotensive response to a change in posture was found in pre-cirrhotic portal hypertensive rats, whereas an inverted hypertensive pressor response in the face of systemic hypotension occurred in the cirrhotic rats with portal hypertension.

4. The inverted pressor response was abolished in the pithed portal hypertensive cirrhotic rats.

5. The pressor response to noradrenaline in vivo in conscious cirrhotic rats and the vascular contractile responsiveness to noradrenaline in vitro were intact.

6. We conclude that blunted responsiveness to noradrenaline is not a contributory factor to the development of systemic hypotension or the inverted pressor response to a change in posture in cirrhosis.
Responsiveness of superficial hand veins to α-adrenoceptor agonists in insulin-dependent diabetic patients
Authors: Eichler Hans-Georg , Blaschke Terrence F. , Kraemer Fredric B. , Ford Gary A. , Blöchl-Daum Brigitte , Hoffman Brian B.
Published: August 2015

1. Diabetic autonomic neuropathy causes loss of sympathetic cardiovascular control and is associated with increased vascular sensitivity to catecholamines. Supersensitivity to catecholamines could be due to either a postsynaptic increase in vascular sensitivity or to decreased catecholamine uptake into peripheral sympathetic nerve endings.

2. To differentiate between these possible mechanisms we have measured the responsiveness in vivo to noradrenaline and phenylephrine with local infusions into peripheral veins of diabetic patients with and without symptomatic autonomic neuropathy and of healthy control subjects. The dorsal hand vein compliance technique was used.

3. Symptomatic diabetic patients required significantly lower doses of noradrenaline for half-maximal venoconstriction (ED50) (geometric mean 2.14 ng/min) than control subjects (geometric mean 6.61 ng/min, P = 0.032), but there was no difference in the results from the phenylephrine dose-response curves between the groups. Thesre were no differences in venous responsiveness to noradrenaline or phenylephrine between the asymptomatic diabetic group and the control group. However, in the asymptomatic diabetic group, postural blood pressure change (an index of loss of sympathetic control) was correlated with the ED50 for noradrenaline (r = 0.74, P = 0.014), but not with the ED50 for phenylephrine. In the control group the ED50 values for noradrenaline and phenylephrine were correlated with each other (r= 0.81, P= 0.0005).

4. Both vasopressor drugs act on vascular α-adrenoceptors, but only noradrenaline is taken up into peripheral sympathetic nerve endings. Our results suggest that, in diabetic patients, vascular supersensitivity to catecholamines is primarily determined by decreased neuronal catecholamine uptake. A postsynaptic increase in vascular a-adrenoceptor stimulation does not appear to be prominent in diabetic autonomic neuropathy.
Vascular responses and ion exchange in diabetes
Authors: Wardle E. N.
Published: August 2015

The use of erythrocyte Na+/Li+ countertransport as a gold standard, as in the article by Halkin et al. (Clin. Sci. 1991; 81, 223–32) [1], should give rise to disquiet because it has been known for a long time that this parameter is influenced by low-density lipoprotein (LDL), by cholesterol and by saturated fatty acids. Recently, it has been clarified that LDL increases the Vmax of this flux [2]. One has to agree that it is interesting that there is an inverse relationship between the ability to dilate blood vessels and Na+/Li+ exchange in the diabetic patient, but actually the basis for this apparent relationship is already known and it is not quite as direct as the authors might wish to imply.

It is not native LDL but oxidized LDL [3] that stops the formation of endothelium-derived relaxing factor (EDRF) [4], reduces prostacyclin production and even enhances ‘tissue factor' formation by endothelial cells [5]. In fact, the reduced production of EDRF by diabetic patients that is pertinent to atherogenesis can be correlated with a raised plasma level of cholesterol [6] and also with the plasma level of lipid peroxides [7].

In that case there is some basic information missing concerning the effects of lipid peroxides on Na+/Li+ fluxes in erythrocytes. When this is known, it might well explain why this parameter seems to relate to hypertension and/or nephropathy in diabetic patients.

Meantime, in a study of this kind [1] we should have been told which of the subjects were smokers, especially as there were two outstanding points on each graph that formed the relationship.
α-Adrenoceptor blockade by phentolamine inhibits adrenaline-induced platelet activation in vivo without affecting resting measurements
Authors: Larsson P. T. , Wallén N. H. , Egberg N. , Hjemdahl P.
Published: August 2015

1. The effects of phentolamine (500 μg/min) on platelet aggregability in vivo at rest and during adrenaline infusion were assessed by ex vivo filtragometry and measurements of plasma β-thromboglobulin levels in 10 healthy male subjects. Plasma levels of von Willebrand factor antigen and free fatty acids were also measured.

2. Adrenaline induced marked and expected increases in heart rate and systolic blood pressure and decreased diastolic blood pressure when venous plasma adrenaline levels were elevated from 0.12 ± 0.02 to 2.9 ± 0.3 nmol/l (P < 0.01).

3. Adrenaline caused platelet activation in vivo. Ex vivo filtragometry readings were shortened by 58 ± 9% (P < 0.01), plasma β-thromboglobulin levels increased by 99 ± 44% (P < 0.01) and platelet counts increased by 26 ± 6% (P < 0.01). Plasma levels of von Willebrand factor antigen and free fatty acids increased by 53 ± 5% and 475 ± 113% (both P < 0.01), respectively.

4. Phentolamine enhanced the β-adrenergic vasodilator responses to adrenaline, as both the decrease in diastolic blood pressure and the reflexogenic increase in heart rate were enhanced (both P < 0.01). Marked elevations in plasma noradrenaline levels were found during infusions of phentolamine and adrenaline (P < 0.001).

5. Phentolamine did not alter platelet indices at rest, but abolished adrenaline-induced platelet activation, as filtragometry readings, plasma β-thromboglobulin levels and platelet counts remained at, or below, resting levels. Responses of plasma levels of von Willebrand factor antigen and free fatty acids to adrenaline were not influenced by phentolamine and did not seem to influence platelet responses.

6. Thus, platelet activation by adrenaline in vivo is mediated via α-adrenoceptors, apparently with minor influences of other physiological responses. Circulating and/or locally released catecholamines may activate platelets directly via α-adrenoceptor stimulation during stressful physiological and pathophysiological conditions in humans.
Platelet cytosolic free calcium concentration and parathyroid hormone: changing relationships with haemodialysis in end-stage renal disease
Authors: Fluck R. J. , McMahon A. C. , Alameddine F. M. , Dawnay A. B. S. , Baker L. R. I. , Raine A. E. G.
Published: August 2015

1. Twelve patients receiving haemodialysis for end-stage renal failure were studied at a single dialysis session. Platelet cytosolic calcium concentration, plasma ionized calcium concentration and serum parathyroid hormone concentration were measured before dialysis, mid-dialysis and 30 min after dialysis.

2. Plasma ionized calcium concentration increased towards dialysate calcium concentrations, falling insignificantly after cessation of dialysis. Serum parathyroid hormone concentration fell by 39% during dialysis, with incomplete recovery afterwards. There was no overall change in platelet cytosolic calcium concentration.

3. Patients were divided into two subgroups: low parathyroid hormone (serum parathyroid hormone concentration < 10 pmol/l) and high parathyroid hormone (serum parathyroid hormone concentration > 10 pmol/l). Before dialysis, values of platelet cytosolic calcium concentration or plasma ionized calcium concentration were not statistically different between the subgroups, but the platelet cytosolic calcium concentration was higher in the high-parathyroid hormone subgroup during and after dialysis.

4. Before haemodialysis there was a linear correlation between plasma ionized calcium concentration and platelet cytosolic calcium concentration, which disappeared during dialysis. In contrast, there was no relationship between serum parathyroid hormone concentration and platelet cytosolic calcium concentration before dialysis, but after dialysis a hyperbolic relationship was evident.

5. These results suggest that uraemic toxins may interfere with cytosolic calcium homoeostasis, allowing passive diffusion of extracellular calcium to influence the resting concentration, and that this effect is reversible by haemodialysis.
Hypertension in Dahl salt-sensitive rats: biochemical and immunohistochemical studies
Authors: Bouhnik J. , Richoux J. P. , Huang H. , Savoie F. , Baussant T. , Alhenc-Gelas F. , Corvol P.
Published: August 2015

1. The renin-angiotensin and kinin-kallikrein systems of Dahl salt-sensitive and salt-resistant rats fed diets with different salt contents were analysed using biochemical and immunocytochemical techniques.

2. Blood pressure increased by 45% in salt-sensitive rats only, after 4 weeks on a high-salt diet. The plasma renin activity and plasma angiotensin II concentration remained at the same levels in salt-sensitive rats on the high-salt diet as on the normal salt diet, whereas the plasma renin activity and plasma angiotensin II concentration of salt-resistant rats fed the high-salt diet were lower. The plasma renin activity and the plasma angiotensin II concentration were elevated in both salt-resistant and salt-sensitive rats fed the salt-deficient diet but were much more elevated in salt-resistant than in salt-sensitive rats.

3. The kidney immunocytochemical data paralleled the data on plasma parameters. Salt-sensitive rats had fewer renin positive juxtaglomerular apparatuses than salt-resistant rats on the normal diet, and the increase on the sodium-deficient diet was also smaller in salt-sensitive rats. Salt-sensitive rats fed the high-salt diet and the standard diet had almost no angiotensin II immunoreactivity compared with the salt-resistant rats on the same diets.

4. The total renal kallikrein content of salt-sensitive rats was lower than that of salt-resistant rats on all three diets, as was the amount of kallikrein excreted in the urine on the standard and the high-salt diets. The differences resulted from a reduction in active kallikrein. The increase in kallikrein in salt-sensitive and salt-resistant rats on the salt-deficient diet was not significantly different.

5. There were similar changes in immunopositive kallikrein in the kidneys of salt-sensitive and salt-resistant rats with diet, with a large increase in kallikrein biosynthesis on the low-salt diet. The plasma concentration of high-molecular-mass kininogen was not significantly different in salt-sensitive and salt-resistant rats, but there was a significant increase in T-kininogen in salt-sensitive rats fed the high-salt diet.

6. In conclusion, the absence of decreases in the plasma renin activity and the plasma angiotensin II concentration in salt-sensitive rats fed the high-salt diet might partially explain the increase in blood pressure.
Atrial natriuretic peptide inhibits fluid intake in hyperosmolar subjects
Authors: Burrell Louise M. , Palmer J. M. , Baylis P. H.
Published: August 2015

1. The effect of atrial natriuretic peptide on osmotically stimulated thirst appreciation and consequent fluid intake was investigated in healthy man.

2. Six seated male subjects were studied on two occasions: synthetic α-human atrial natriuretic peptide (99–126) (2 pmol min−1kg−1) or placebo (saline, 150 mmol/l NaCl) was infused intravenously for 105 min; 30 min after the start of atrial natriuretic peptide/placebo infusion, hypertonic saline (855 mmol/l NaCl) was infused (0.06 ml min−1 kg−1) for 60 min. Subjects were then allowed free access to water for the next 2 h; infusion of atrial natriuretic peptide/ placebo continued for the first 15 min of the drinking period.

3. The plasma atrial natriuretic peptide concentration did not alter significantly during infusion of hypertonic saline and placebo; it rose to a steady state of 12.7 ± 1.1 pmol/l (mean ± SEM) during the infusion of atrial natriuretic peptide and hypertonic saline, and remained at this level during the first 15 min of the drinking period. During infusion of hypertonic saline and atrial natriuretic peptide or placebo, similar increases in plasma osmolality (P < 0.001) and plasma vasopressin concentration (P < 0.005) occurred. During infusion of hypertonic saline and atrial natriuretic peptide or placebo, thirst increased significantly over the time course of both studies (P<0.01), but the effect of atrial natriuretic peptide infusion compared with placebo infusion was to significantly decrease thirst at 60 min.

4. Drinking rapidly abolished thirst and vasopressin secretion before changes in plasma osmolality occurred. Subjects drank significantly less water after atrial natriuretic peptide infusion compared with after placebo infusion (P<0.01).

5. In conclusion, physiological increases in plasma atrial natriuretic peptide concentrations blunt osmotically stimulated thirst appreciation and attenuate subsequent fluid intake in hyperosmolar man.
Comparisons between basal metabolic rate and diet-induced thermogenesis in different types of chronic obstructive pulmonary disease
Authors: Green J. H. , Muers M. F.
Published: August 2015

1. Some patients with the emphysematous type of tobacco-related chronic obstructive pulmonary disease are hypermetabolic. Since the likely mechanism is the increased work of breathing, other groups of patients with chronic obstructive pulmonary disease should be similar. We have now measured basal metabolic rate and diet-induced thermogenesis in six patients with chronic obstructive pulmonary disease with an arterial partial pressure of CO2 of <5kPa (emphysematous), nine patients with chronic obstructive pulmonary disease with an arterial partial pressure of CO2 of >6kPa (bronchitic), eight patients with chronic obstructive pulmonary disease due to chronic asthma and seven control subjects. Diet-induced thermogenesis was measured for 4h after a meal of 87% carbohydrate, 11% protein and 2% fat as energy, with a total energy content of 40% of basal metabolic rate.

2. There was no difference between measured and predicted basal metabolic rate in the control (5541 ± 272 versus 5881 ± 245 kJ/24h) or emphysematous (5552 ± 370 versus 6239 ± 197 kJ/24 h) groups, but measured basal metabolic rate was significantly higher than predicted in the bronchitic (6126 ± 387 versus 5405 ± 250 kJ/24 h) and asthmatic (6293 ± 197 versus 5701 + 245, mean ± SEM, P<0.01) groups. All the control subjects had measured basal metabolic rates within 10% of predicted, whereas two out of six emphysematous patients, four out of nine bronchitic patients and five out of eight asthmatic patients were hypermetabolic. The contributions of fat, carbohydrate and protein oxidation rates to the overall basal metabolic rate were similar between groups.

3. Diet-induced thermogenesis was similar between groups. The postprandial fuel mix oxidized was also similar between all four groups.

4. Thus, some patients with both types of smoking-related chronic obstructive pulmonary disease and other patients with chronic asthma were hypermetabolic. This could not be predicted from detailed lung function tests, arterial blood gases or anthropometric measurements, and suggests that the increased work of breathing may not be the only cause of the hypermetabolism and weight loss seen in these patients.
Effects of endothelin in portal hypertensive rats
Authors: Yu Pi-Chin , Kuo Jon-Son , Lin Han-Chieh , Yang May C. M.
Published: August 2015

1. Effects of endothelin-1 on systemic arterial blood pressure, heart rate and portal venous pressure were compared in normal Sprague-Dawley rats and rats with portal hypertension induced by CCl4 and partial portal vein ligation.

2. Endothelin-1 produced biphasic effects on systemic blood pressure and portal venous pressure in all three groups of rats. However, the magnitude of the changes in blood pressure was less in portal hypertensive rats.

3. The ability of endothelin-1 to increase the portal venous pressure was also significantly diminished in portal hypertensive rats. On the other hand, the initial decrease in portal pressure was augmented in rats with partial portal vein ligation, and disappeared at higher dosage in CCl4-treated rats.

4. In accordance with the pressure recording in vivo, the dose-response vasoconstrictive activity of endothelin-1 was significantly attenuated in the intrahepatic vasculature.

5. The plasma immunoreactive endothelin concentration was significantly higher (5.55 ± 0.81 fmol/ml) in Sprague-Dawley rats than in CCl4-treated rats (2.83 ± 0.56 fmol/ml) and rats with partial portal vein ligation (2.68 ± 0.53 fmol/ml).

6. It was concluded that a lower plasma level of endothelin and a reduced vascular responsiveness may contribute, at least in part, to the hyperdynamics of portal hypertension.
Resting energy expenditure and the thermic effect of adrenaline in patients with liver cirrhosis
Authors: Müller Manfred J. , Willmann Olaf , Fenk Andrea , Rieger Annette , Selberg Oliver , Canzler Helmut , von zur Mühlen Alexander , Schmidt Friedrich W.
Published: August 2015

1. Resting energy expenditure and the metabolic responses to adrenaline (infusion rate: 0.03 μg min−1 kg−1 fat-free mass for 1 h) were investigated in 25 patients with liver cirrhosis. The patient group was heterogeneous and varied with respect to the aetiology of cirrhosis, the clinical condition (i.e. Child A or B), the nutritional status and the degree of hyper-insulinaemia.

2. When compared with 10 healthy control subjects the basal plasma adrenaline and noradrenaline concentrations were both increased in cirrhosis and remained elevated during adrenaline infusion (+39% and +31%, respectively; P<0.05). Concomitantly, the peripheral plasma insulin concentration and the molar C-peptide/insulin ratio were increased in liver cirrhosis (+96% and + 30%, respectively; P<0.05). Hyperinsulinaemia was more pronounced in patients with ethanol-induced liver cirrhosis.

3. When expressed per kg fat-free mass, resting energy expenditure was enhanced in liver cirrhosis (+21%; P<0.05) and was more pronounced (i.e. resting energy expenditures of +35% to +49% above estimated values) in patients with ethanol-induced cirrhosis, at advanced stages of the disease and in association with decreased body cell mass.

4. Infusion of adrenaline increased heart rate, O2 consumption and the plasma concentrations of glucose, lactate, free fatty acids, glycerol and 3-hydroxybutyrate, and similar transient increases and subsequent decreases in the respiratory quotient were observed in both groups. However, the lipolytic, ketogenic and thermic responses were reduced in cirrhotic patients. Reduced metabolic responses were more pronounced in hyperinsulinaemic patients.

5. We conclude that resting energy expenditure is variable but may be substantially increased in patients with ethanol-induced cirrhosis. In contrast, the thermic effect of adrenaline is reduced in cirrhotic patients. Variations in resting energy expenditure are strongly associated with variations in body cell mass, which explains 65% of its variability. No parameter of body composition is predictive for thermogenesis.
Aggregation of erythrocyte sodium/lithium countertransport activity in families of patients with immunoglobulin A nephropathy
Authors: Fabbri A. , Boero R. , Esposti E. Degli , Guarena C. , Lucatello A. , Sturani A. , Piccoli G. , Fusaroli M.
Published: August 2015

1. We evaluated the inheritance of erythrocyte Na+/Li+ countertransport activity in IgA nephropathy by assessing this parameter in 19 patients with biopsy-proven IgA nephropathy and in their 53 relatives (32 parents and 21 siblings). The possible use of erythrocyte Na+/Li+ countertransport activity as a marker of poor prognosis was also evaluated.

2. A significant correlation was found between ‘familial’ and proband Na+/Li+ countertransport activity, but not between that of spouses.

3. Mean blood pressure, although within the normal range, and Na+/Li+ countertransport activity were significantly higher in patients with proteinuria than in those without proteinuria.

4. Parents of proteinuric patients had a higher Na+/Li+ countertransport activity than parents of non-proteinuric patients.

5. In IgA nephropathy the inheritance of erythrocyte Na+/Li+ countertransport activity was preserved. Therefore genetic factors could play a role in the non-immunological progression of IgA nephropathy.
Pancreatic secretion of lysosomal enzymes stimulated by intraduodenal instillation of a liquid meal in rabbits
Authors: Hirano T. , Manabe T. , Saluja A. K. , Steer M. L.
Published: August 2015

1. Studies have been performed to determine the effect of intraduodenal food on pancreatic secretion of lysosomal enzymes.

2. Intraduodenal instillation of a liquid meal (3 g/kg body weight; 15.3% protein, 19.7% fat, 59.7% carbohydrate) caused significant increases in pancreatic juice volume and pancreatic secretion of amylase and protein compared with basal values for 2 h after instillation in anaesthetized rabbits.

3. Intraduodenal instillation of a liquid meal also caused significant increases in pancreatic secretion of three lysosomal enzymes (cathepsin B, N-β-acetyl-galactosaminidase and N-acetyl-β-glucosaminidase) compared with basal values for 2 h after instillation.

4. In addition, there were significant correlations between cathepsin B secretion and amylase secretion (r = 0.7764, P<0.001) and between cathepsin B secretion and protein secretion (r = 0.6216, P<0.001), both in basal conditions and in response to the liquid meal.

5. These results are evidence for the localization of lysosomal enzymes in the secretory granules-zymogen granules in normal acinar cells, and also indicate that the pancreatic secretion of lysosomal enzymes is gut-hormone-regulated.
Altered prostaglandin synthesis and impaired sodium conservation in the kidneys of old rats
Authors: Rathaus M. , Greenfeld Z. , Podjarny E. , Brezis M. , Green J. , Bernheim J.
Published: August 2015

1. The aim of this investigation was to study the role of prostaglandins in the impaired Na+ conservation of the ageing kidney.

2. We measured the urinary excretion of thromboxane B2, 6-keto-prostaglandin F1α and prostaglandin E2 in young (3–4 months) and old (20–21 months) rats after 12, 24 and 36 h of Na+ deprivation. In a separate protocol, we measured prostanoid synthesis by isolated glomeruli, cortical homogenates, medullary slices and papillary slices from young and old rats in basal conditions and after 15 days of dietary Na+ deprivation.

3. In the acute study, urinary excretion of 6-ketoprostaglandin F1α and prostaglandin E2 decreased in young but not in old rats. Urinary excretion of prostaglandin E2 was lower in old rats, but did not vary significantly with Na+ deprivation.

4. In old rats, thromboxane B2 synthesis was increased in all the portions of the kidney except the medulla. Production of 6-keto-prostaglandin F1α was elevated in glomeruli and tended to increase in the cortex. Prostaglandin E2 synthesis was also elevated in the cortex. Thromboxane B2 synthesis tended to increase in the medulla and was enhanced in the papilla. After Na+ deprivation, only glomerular prostaglandin E2 synthesis increased in young rats. In old rats, cortical and papillary synthesis of 6-ketoprostaglandin F1α increased, whereas prostaglandin E2 synthesis did not change.

5. The results suggest increased thromboxane synthesis in the ageing kidney. Increased prostacyclin and prostaglandin E2 synthesis may be an attempt to counteract enhanced thromboxane production. Blunting of this tendency in medulla and papilla could contribute to the conservation of medullary solute concentration, whereas inappropriate stimulation of prostacyclin synthesis during Na+ deprivation could impair Na+ conservation.
Sodium-lithium countertransport and platelet cytosolic free calcium concentration in relation to peripheral insulin sensitivity in postmenopausal women
Authors: Mattiasson Ingrid , Berntorp Kerstin , Lindgärde Folke
Published: August 2015

1. Peripheral glucose disposal (assessed by the euglycaemic-hyperinsulinaemic clamp technique), Na+-Li+ countertransport in erythrocytes and the cytosolic free Ca2+ concentration in platelets were determined in 41 women with impaired glucose tolerance and in 38 women with normal glucose tolerance. The groups were matched for body mass index (range 18–44 kg/m2) and diastolic blood pressure (range 58–109 mmHg).

2. Na+-Li+ countertransport was correlated significantly with body mass index, basal plasma insulin concentration and basal plasma glucose concentration, and was inversely correlated with peripheral glucose disposal rate. Stepwise regression analysis showed that Na+-Li+ countertransport was positively correlated with basal plasma insulin concentration (r2 = 8.7%).

3. Systolic blood pressure was correlated with fasting plasma insulin concentration (model r2 = 25%) and with Na+-Li+ countertransport (model r2 = 34%) in the group with impaired glucose tolerance. In the group with normal glucose tolerance there were no correlations between blood pressure and Na+-Li+ countertransport.

4. No correlation was found between platelet cytosolic free Ca2+ concentration and any of the variables measured.

5. It is concluded that Na+-Li+ countertransport is correlated with the degree of peripheral insulin sensitivity and with the plasma insulin concentration. Platelet cytosolic free Ca2+ concentration was not correlated with any of these variables, and there was no relationship between Na+-Li+ countertransport and the platelet cytosolic free Ca2+ concentration.
Study of the actions of human recombinant erythropoietin on rat renal haemodynamics
Authors: Huang Chunlong , Davis Gerard , Johns Edward J.
Published: August 2015

1. Studies were undertaken to examine the effect of acute and chronic administration of human recombinant erythropoietin on kidney cortical and papillary perfusion in the anaesthetized rat using laser-Doppler flowmetry.

2. Thirty minutes after erythropoietin (50 and 150 units/kg intravenously), blood pressure, cortical perfusion and papillary perfusion were unchanged.

3. In animals treated chronically with erythropoietin over 7 days (three doses of 150 units/kg subcutaneously) blood pressure was similar to that of vehicle-treated animals, whereas cortical perfusion and papillary perfusion were reduced by 23% and 20%, respectively (both P<0.05), and the packed cell volume (51.1 ± 0.7%) was significantly (P<0.01) greater than in vehicle-treated animals (46.2 ± 0.6%).

4. Bolus doses of vasopressin and phenylephrine increased blood pressure (by between 10% and 40%) and decreased cortical and papillary perfusion (by between 10% and 20%), while angiotensin II caused similar increases in blood pressure and decreases in cortical perfusion but not papillary perfusion. The magnitude and pattern of these responses were comparable after both acute and chronic administration of erythropoietin.

5. Erythropoietin given acutely at therapeutic levels has a marginal effect on cortical and papillary perfusion. However, the chronic treatment indicated that there was a sustained reduction in both cortical and papillary perfusion, reflecting a vasoconstriction. This reduction in renal haemodynamics could contribute to the increase in blood pressure observed when this hormone is administered in man.
Generation of angiotensin II from human plasma by tissue kallikrein
Authors: Krivoy N. , Schlüter H. , Karas M. , Zidek W.
Published: August 2015

1. Human plasma was incubated with tissue kallikrein from porcine pancreas, dialysed to obtain a fraction with a molecular mass < 10 kDa and further purified by reverse-phase chromatography.

2. Vasopressor activity in the fractions obtained was tested in the isolated perfused rat kidney.

3. In one fraction a strong vasopressor action was found, which was blocked by saralasin and by an angiotensin II antibody.

4. Aprotinin inhibited the formation of vasopressor substances by tissue kallikrein.

5. U.v.-laser desorption/ionization mass spectrometry revealed a molecular mass of 1046 Da in the purified active fraction.

6. It is concluded that tissue kallikrein forms not only kinins, but also angiotensin II, from human plasma under physiological conditions.