bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancement of specific [3H]ouabain binding and ouabain sensitive 86rubidium influx in intact human lymphocytes by a dialysable factor in human and fetal calf serum
Authors: Oh V. M. S. , Taylor E. A. , Ding J. L. , Boon N. A. , Aronson J. K. , Grahame-Smith D. G.
Published: August 2015

1. We have measured specific [3H]ouabain binding and ouabain sensitive 86rubidium influx in intact human lymphocytes incubated for up to 7 days in media containing different concentrations of fetal calf serum and human serum.

2. Incubation for periods of up to 7 days with fetal calf serum and human serum produced increases in both specific [3H]ouabain binding and ouabain sensitive 86rubidium influx that were dependent on concentration and time.

3. Neither specific [3H]ouabain binding nor ouabain sensitive 86rubidium influx was altered when dialysed serum was used, suggesting that both fetal calf serum and human serum contain a dialysable factor or factors which stimulate specific [3H]ouabain binding and ouabain sensitive 86rubidium influx in intact human lymphocytes.

4. To further elucidate the mechanisms underlying these changes we also measured the activity of two other enzymes of the lymphocyte plasma membrane, 5′-nucleotidase and γ-glutamyltransferase, the uptake of [3H]thymidine by the intact cells, and the effects of cycloheximide, puromycin, and anisomycin, inhibitors of protein synthesis.

5. The activity of 5′-nucleotidase was increased after incubation of the lymphocytes in fetal calf serum for 72 h, but the activity of γ-glutamyltransferase was not changed, suggesting some selectivity of the stimulatory effect.

6. Measurements of [3H]thymidine uptake by the lymphocytes showed that the major part of the observed changes in specific [3H]ouabain binding and ouabain sensitive 86rubidium influx was not attributable to transformation of the lymphocytes to lymphoblasts.

7. All three inhibitors of protein synthesis prevented the increase in specific [3H]ouabain binding due to fetal calf serum.
Adrenergic control of plasma magnesium in man
Authors: Whyte Kenneth F. , Addis George J. , Whitesmith Robert , Reid John L.
Published: August 2015

1. Regulation of magnesium balance is poorly understood. However, hypomagnesaemia has been reported in patients in clinical situations where circulating catecholamines are raised including myocardial infarction, cardiac surgery and insulin-induced hypoglycaemia stress tests.

2. The effects of l-adrenaline infusions, sufficient to achieve pathophysiological levels of adrenaline, and of therapeutic intravenous infusions of salbutamol, a β2-agonist, on plasma magnesium, plasma potassium, plasma glucose and plasma insulin levels were studied in a placebo-controlled design in eight normal subjects.

3. Plasma magnesium levels fell significantly during the adrenaline infusion and also during the salbutamol infusion, though more slowly. In a 1 h period of observation after cessation of the infusions no recovery of plasma magnesium levels was seen. Significant falls in plasma potassium levels were also observed during both infusions with spontaneous recovery within 30 min after the infusions.

4. No significant changes in plasma insulin levels occurred with either salbutamol or l-adrenaline compared with control. Plasma glucose levels rose significantly during the adrenaline infusion.

5. The study suggests that both l-adrenaline and salbutamol cause shifts in plasma magnesium which are not mediated by insulin. We propose that intracellular shifts of magnesium occur as a result of β-adrenergic stimulation.
Plasma atrial natriuretic peptide concentrations during exercise in sodium replete and deplete normal man
Authors: Richards A. M. , Tonolo G. , Cleland J. G. F. , McIntyre G. D. , Leckie B. J. , Dargie H. J. , Ball S. G. , Robertson J. I. S.
Published: August 2015

1. To explore the effects of exercise on plasma atrial natriuretic peptide (ANP) concentrations, eight normotensive volunteers performed maximal treadmill exercise in sodium replete and deplete states.

2. Baseline immunoreactive plasma ANP concentrations were significantly lower during sodium depletion. During exercise plasma ANP rose in all subjects on both occasions. Plasma peptide responses were attenuated by sodium depletion with peak exercise levels only double baseline values, in contrast to the threefold increase in ANP concentrations observed when subjects were sodium replete.

3. Plasma renin and aldosterone concentrations also rose with exercise. In contrast to changes in plasma ANP, the responses of both were enhanced by sodium depletion.
Intrathyroidal autonomic nerves can directly influence hormone release from rat thyroid follicles: A study in vitro employing electrical field stimulation and intracellular microelectrodes
Authors: Green Stephen T.
Published: August 2015

1. The role of the autonomic nervous system in the control of thyroxine release from the rat thyroid gland in vitro, has been investigated using electrical field stimulation as a device to induce intrathyroidal nerves to release their neurotransmitters.

2. The effects of field stimulation on follicular cell membrane potential and input resistance have been investigated using continuous intracellular recordings from individual cells.

3. Electrical field stimulation promotes up to an eightfold increase in throxine release from the thyroid gland in vitro. This effect is blocked by the neurotoxin, tetrodotoxin.

4. Electrical field stimulation has no effect on follicular cell membrane potential or input resistance. This is consistent with the results of previous pharmacological experiments using this preparation.

5. It is concluded that electrical field stimulation induces intrathyroidal nerves to release their neurotransmitters, and that the net effect of this is to cause thyroxine release from the thyroid follicles. The existence of a directly acting secretomotor innervation to the thyroid follicle is suggested.
Effects of ethanol ingestion on blood pressure reactivity
Authors: Eisenhofer G. , Lambie D. G. , Johnson R. H.
Published: August 2015

1. We examined the acute effects of ethanol consumption on circulatory responses to the cold pressor test, to handgrip exercise and to intravenous infusion of methoxamine in eight normal male subjects.

2. Ethanol consumption reduced systolic blood pressure responses to the cold pressor test and to handgrip exercise and depressed both systolic and diastolic blood pressure responses to infusion of methoxamine. The depressant effects of ethanol on blood pressure responses to methoxamine were considerably greater than the effects on the cold pressor test and handgrip exercise. Catecholamine concentrations during the cold pressor test and handgrip exercise were not significantly different with or without prior ethanol consumption.

3. Alcohol has been shown to have an acute hypotensive action with all the stimuli.
Oral absorption of the somatostatin analogue SMS 201–995: Theoretical and practical implications
Authors: Fuessl Hermann S. , Domin Jan , Bloom Stephen R.
Published: August 2015

1. Oral administration of SMS 201–995 (SMS), a subcutaneously injectable somatostatin analogue, was investigated in five healthy volunteers, who drank 2 mg of SMS with 75 g of glucose.

2. Mean maximal plasma SMS concentrations after the 2 mg oral dose were comparable with those after subcutaneous injection of 50 μg, although the peak was delayed (90 vs 15 min).

3. Biological activity of absorbed SMS was shown by significant and lasting suppression of plasma insulin concentrations, resulting in significant hyperglycaemia at 90 and 120 min compared with the control study.

4. The feasibility of oral administration of SMS may extend its use in the treatment of acromegaly and gut endocrine tumours. Other peptide hormone analogues, structurally ‘protected’ against enzymatic degradation, may also be active orally and thus be useful therapeutically.
Cardiac and renal hyperplasia in newborn spontaneously hypertensive rats
Authors: Kunes Jaroslav , Pang Stephen C. , Cantin Marc , Genest Jacques , Hamet P.
Published: August 2015

1. Cardiac hyperplasia in newborn spontaneously hypertensive rats (SHR) has been noted by our group as well as by other investigators. The present study was designed to establish whether early (neonatal) hyperplasia is confined to the heart or is a generalized phenomenon in this hypertensive model.

2. The ventricles, kidney and liver of newborn SHR, Wistar and Wistar-Kyoto (WKY) rats were analysed for their protein and DNA content.

3. Total organ weight and the organ/body weight ratio of the heart and kidney but not of the liver were significantly greater in the SHR than in the control rats, irrespective of total body weight.

4. The higher relative DNA content (per 100 mg of tissue or 100 g body weight) indicated that hyperplasia rather than hypertrophy was responsible for the enlarged heart as well as the kidney of newborn SHR.

5. The cause of this selective cardiac and renal hyperplasia is not yet known: it may be due to putative ‘haemodynamic growth stimuli’, an intrinsic genetic abnormality of cells in the heart and kidney, circulating growth-promoting factors, or innervation.
Atrial natriuretic peptide: Evidence of action as a natriuretic hormone at physiological plasma concentrations in man
Authors: Anderson J. V. , Donckier J. , Payne N. N. , Beacham J. , Slater J. D. H. , Bloom Pr S. R.
Published: August 2015

1. The administration of exogenous atrial natriuretic peptide (ANP) causes a natriuresis and diuresis in man, but this has, to date, only been demonstrated at plasma ANP concentrations within the high pathological or pharmacological ranges. Evidence that ANP acts physiologically requires the demonstration of a natriuretic effect when it is infused to recreate plasma concentrations similar to those observed after physiological stimuli.

2. We infused human α-ANP (1–28) at a calculated rate of 1.2 pmol min−1 kg−1 for 3 h into seven water-loaded normal subjects, achieving plasma ANP concentrations within the upper part of the physiological range. The subjects' resting plasma ANP concentration increased from 3.8 ± 1.5 to 20.9 ± 1.9 pmol/l.

3. The infusion of ANP caused a 60% increase of mean urinary sodium excretion from 111 ± 18 to 182 ± 30 μmol/min (P < 0.001) and a 28% increase of mean water excretion from 10.8 ± 0.8 to 13.8 ± 1.6 ml/min (P < 0.01).

4. The infusion suppressed mean plasma renin activity from 1.55 ± 0.10 to 1.17 ± 0.06 pmol of ANG I h−1 ml−1 (P < 0.001). Mean plasma aldosterone concentration (242 ± 16 basally and 215 ± 15 pmol/l at the end of ANP infusion) did not change significantly. Pulse rate and blood pressure were unchanged throughout the study.

5. No significant change in any of the variables mentioned above occurred during the infusion of the vehicle alone on a separate study day.

6. The demonstration that recreation of plasma concentrations of ANP within the physiological range by intravenous infusion induces a natriuresis provides new evidence supporting the role of ANP as a natriuretic hormone.
Reduced brain Na+,K+-ATPase activity in rats with galactosamine-induced hepatic failure: relationship to encephalopathy and cerebral oedema
Authors: Ede Roland J. , Gove Christopher D. , Hughes Robin D. , Marshall William , Williams Roger
Published: August 2015

1. Previously we have shown that sera from patients with fulminant hepatic failure (FHF) will inhibit partially purified rat brain Na+,K+-ATPase and sodium efflux from human leucocytes in vitro. Similar inhibition may be involved in the pathogenesis of encephalopathy and cerebral oedema in these patients.

2. In the present study we have attempted to establish whether the activity of brain Na+,K+-ATPase is decreased in vivo in rats with d-galactosamine induced hepatic failure using homogenates of snap-frozen brains.

3. Na+,K+-ATPase activity was significantly reduced in the forebrain region at the stage of mild encephalopathy (43 h after injection), while at the deeper stage of coma (43–53 h after injection) enzyme activity was further reduced in the forebrain region and was also significantly reduced in the hindbrain region. Ouabain insensitive ATPase activity was not significantly altered at any time.

4. While a significant increase in the water content (0.5%) of the hindbrain region was found 43 h after galactosamine, there was no clear correlation between the development of cerebral oedema and the reduction of Na+,K+-ATPase activity.

5. The activity of partially purified normal rat brain Na+,K+-ATPase was 15% lower when incubated with sera from rats in the deep stage of coma compared with control sera.

6. These data support other evidence that the reduction in brain Na+,K+-ATPase is likely to be due to toxic substance circulating in serum which have been shown to inhibit this enzyme in vitro and to cause coma when administered to normal animals.
Effect of dietary linoleate content on the metabolic response of rats to Escherichia coli endotoxin
Authors: Wan Jennifer M. , Grimble R. F.
Published: August 2015

1. Dietary fat influences many aspects of immune function. Escherichia coli endotoxin is a potent stimulator of interleukin 1 production from macrophages.

2. The present study examines the effect of feeding with fat diets rich (corn oil) and poor (coconut oil) in linoleate at high and low concentrations on responses to endotoxin.

3. Spleen phosphatidylcholine linoleate contents were higher in the corn oil than in the coconut oil group and arachidonate concentrations were highest in the group fed a high concentration of corn oil.

4. Coconut oil completely abolished the responses to endotoxin.

5. The inhibitory effects of coconut oil could largely be due to reduced prostaglandin and leukotriene synthesis.
The ulcerogenic and protective action of rice and rice fractions in experimental peptic ulceration
Authors: Jayaraj A. P. , Tovey F. I. , Clark C. G. , Rees K. R. , White J. S. , Lewin M. R.
Published: August 2015

1. The ulcerogenic and protective effects of various rice fractions in the diet were studied in the pylorus ligated ulcer model in the rat.

2. Oil present in rice and particularly rice bran becomes ulcerogenic on storage and in this model results in a significant increase in the median (range) numbers of ulcers from six (one to ten) to nine (six to 15) (P > 0.05). The ulcerogenic effect of stored rice bran oil was reversed by cysteine which significantly reduced the ulcer incidence from 100% to 60% (P > 0.005) and the numbers of ulcers from 26 (six to 70) to one (zero to four) (P > 0.001).

3. Fresh rice bran significantly reduced the numbers of ulcers from six (one to ten) to one (one to four) (P > 0.05). Similarly, unmilled rice and freshly milled newly harvested rice was also shown to be protective in this model by significantly reducing the ulcer incidence from 87.5% to 50% and 0% respectively (P values > 0.025) and the numbers of ulcers from three (zero to 17) to one (zero to one) and zero (zero to zero) respectively (P values > 0.001).

4. These results could in part explain the geographical distribution of duodenal ulceration, where the incidence is high in all the rice eating areas of the world, and provide a plausible hypothesis to explain the mechanism of dietary ulcerogenesis.
Changes in the plasma levels of atrial natriuretic peptides during mineralocorticoid escape in man
Authors: Cappuccio Francesco P. , Markandu Nirmala D. , Buckley Martin G. , Sagnella Giuseppe A. , Shore Angela C. , MacGregor Graham A.
Published: August 2015

1. Plasma levels of atrial natriuretic peptide (ANP) were measured by radioimmunoassay in eight normal healthy volunteers before and during mineralocorticoid escape.

2. Mean plasma ANP on a fixed sodium intake before fludrocortisone was 6.5± sem 1.1 pg/ml. Within 24 h of fludrocortisone administration there was a significant increase in plasma ANP which continued to increase daily reaching a plateau by day 4 (14.9 ± 2.4 pg/ml) to day 7 (15.1 ± 2.6 pg/ml).

3. The rise in plasma ANP was closely related to the amount of sodium retained during the fludrocortisone treatment and the sodium ‘escape’ occurred by days 4 to 7.

4. These results support the concept that ANP could play an important hormonal role in overcoming the sodium-retaining effects of mineralocorticoids in man.
β-Adrenoceptor blockade and plasma lipoproteins. Comparison of the effects of propranolol and pindolol on plasma lipoproteins including high-density lipoprotein subfractions
Authors: Northcote Robin J. , Ballantyne David
Published: August 2015

1. β-Adrenoceptor blocker therapy is known to cause disturbances of the lipoprotein profile. The long-term effects of β-adrenoceptor blockers and the influence of intrinsic sympathomimetic activity (ISA) has not been clearly defined. We measured serum lipoproteins during chronic β-adrenoceptor blockade in patients with stable angina pectoris treated with propranolol (without ISA) (n = 21) or pindolol (with ISA) (n = 19).

2. No significant changes occurred in the lipoprotein profile of the patients taking pindolol. In those taking propranolol, very low density lipoprotein (VLDL) increased at 52 weeks (P < 0.05) and total high density lipoprotein (HDL) decreased at 26 weeks (P < 0.01) and at 52 weeks (P < 0.05). However, HDL2 rose significantly at 52 weeks (P < 0.05). There was a corresponding increase in HDL2/HDL3 ratio.

3. We conclude that pindolol is less likely to exert a harmful effect on plasma lipoproteins than β-adrenoceptor blockers without ISA.
The relationship between the plasma potassium concentration and renal potassium excretion in the adrenalectomized rat
Authors: West M. L. , Sonnenberg H. , Veress A. , Halperin M. L.
Published: August 2015

1. The purpose of this study was to evaluate the renal mechanisms which lead to a high urine [K+] in adrenalectomized (ADX) rats devoid of aldosterone.

2. By dividing the urine [K+] by the urine to plasma osmolality ratio, the [K+] in the cortical collecting duct luminal fluid can be estimated; dividing this value by the plasma [K+] yields an index of the transtubular [K+] gradient (TTKG) in vivo.

3. The TTKG was close to 7 in aldosterone deficient ADX rats while on a normal K+ diet and fell towards unity when amiloride or a low K+ diet was administered to these rats.

4. With a longer time on a low K+ diet, the TTKG was less than 1 in ADX rats. This suggests that K+ was reabsorbed in the medullary collecting duct under these conditions.

5. Hyperkalemia appears to have an ‘aldosterone-like’ action in the cortical collecting duct in vivo in the absence of aldosterone in ADX rats. This action of hyperkalemia permits normal K+ excretion rates despite the absence of mineralocorticoids.
Bronchial effects of leukotriene D4 inhalation in normal human lung
Authors: Bisgaard Hans , Groth Steffen
Published: August 2015

1. The aim of the study was to investigate whether inhaled leukotriene (LT) D4 could mimic the characteristics of asthmatic patients after allergen-induced attack, i.e. a prolonged subclinical bronchial obstruction, an increased reactivity of the airways and a late reaction. The effects of LTD4 were compared with those of histamine and the mechanism of action sought.

2. Thirty-three non-atopic individuals participated in the study. The two drugs were inhaled as an aerosol of small particles causing a relative peripheral deposition pattern in order to mimic the preferential involvement of peripheral airways in asthmatic patients out of attack.

3. LTD4 caused a dose-dependent obstruction of the airways as measured by partial flow-volume curves and volume of trapped gas, yet only minor changes in forced expiratory volume in 1 s (FEV1) and peak expiratory flow rate. LTD4 was 1900–7000 times more potent than histamine. LTD4 inhalations were almost symptomless as opposed to the irritative and dyspnoeic symptoms seen after inhalation of histamine.

4. The time duration for the induced change in partial flow-volume curves was the same for the two drugs. Approximately 30 min elapsed until the bronchial obstruction had decreased by 50% of the maximum effect, and no delayed reaction was observed within 10 h.

5. The reactivity of the airways did not change during 10 h after inhalation of LTD4 as tested by repeated exercise challenges.

6. Pretreatment with ipratropium bromide prevented the effect of LTD4 on FEV1, yet not on partial flow-volume curves. Pretreatment with either cimetidine and mepyramine or with indomethacin, did not affect the bronchial obstruction after LTD4.

7. In conclusion, peripheral deposition of LTD4 in non-atopic subjects causes symptomless reduction in airflow with changes in lung function imitating that found in asthmatic patients out of attack. Unlike an allergen-induced asthmatic attack, inhalation of LTD4 does not seem to induce bronchial hyper-reactivity to exercise nor a late reaction. These findings are compatible with LTD4 as a mediator involved in bronchial asthma.
Gliadin binding to rat and human enterocytes
Authors: Colyer J. , Kumar P. J. , Waldron N. M. , Clark M. L. , Farthing M. J. G.
Published: August 2015

1. Binding of 125I-crude gluten digest (Frazer's fraction III, FF-III) and 125I-concanavalin A (Con A) to isolated rat enterocytes and of 125I-FF-III to human enterocytes was investigated.

2. Specific binding of 125I-FF-III to rat enterocytes was observed but binding was not inhibited by any of a range of simple and complex saccharides, although casein and bovine serum albumin displaced FF-III at high concentrations.

3. Con A also bound to enterocytes in a specific manner and was inhibited by α-methyl-D-mannoside, confirming a lectin-mediated interaction.

4. 125I-FF-III exhibited quantitatively similar specific binding to both normal human and coeliac enterocytes.

5. The primary interaction of gliadin peptides with the enterocyte surface membrane is not lectin-mediated and unlikely to be of fundamental importance in the pathogenesis of coeliac disease.
Haemodynamic consequences of experimental papillary necrosis in the rat
Authors: Russell Gavin I. , Bing Robert F. , Thurston Herbert , Swales John D.
Published: August 2015

1. Experimental renal papillary necrosis induced by 2-bromoethylamine hydrobromide (BEA) results in hypertension in the rat. The haemodynamics of this increase in blood pressure were investigated with radiolabeled microspheres, thus enabling individual organ blood flows to be evaluated.

2. Total peripheral resistance was raised in BEA-treated rats (3.6 ± 0.3 mmHg ml−1 minm 100 g) compared with control rats (2.87 ± sem 0.2, P < 0.05) whilst cardiac index remained similar (39.9 ± 3.6 vs 39.2 ± 3.1 ml min−1 100g−1).

3. Heart and brain from BEA rats demonstrated a significant rise in vascular resistance with a normal blood flow. In the kidneys vascular resistance increased still further and here there was a reduction in renal blood flow despite an increase in kidney size.

4. These findings are compatible with a loss of renomedullary vasodepressor mechanisms acting directly or indirectly on the resistance vessels.
Influence of cardiopulmonary receptors on the bradycardic responses to carotid baroreceptor stimulation in man
Authors: Parati G. , Grassi G. , Coruzzi P. , Musiari Luisa , Ravogli Antonella , Novarini A. , Mancia G.
Published: August 2015

1. Animal studies have shown that arterial baroreflexes are modulated by reflexes originating from the cardiopulmonary volume receptors, and that this modulation consists of a reduction of the inhibitory influence exerted by arterial baroreceptors on the heart and peripheral circulation. This has not been confirmed in man, however, in whom no reduction in the bradycardic response to carotid baroreceptor stimulation has been observed after the mild increase in central venous pressure (right atrial catheter) and cardiopulmonary receptor activity provided by passive leg raising.

2. In seven normotensive subjects carotid baroreceptors were gradedly stimulated by progressively increasing carotid transmural pressure through a neck chamber device, the resulting reflex lengthening in R–R interval being measured in the two–three cardiac cycles immediately after the baroreceptor stimulus. This manoeuvre was performed in control conditions and repeated during a head-out water immersion which increased central venous pressure (right atrial catheter) from 1.5 ± 0.2 to 12.0 ± 0.9 mmHg (mean ± SE), thereby providing a marked increase in the cardiopulmonary receptor stimulus.

3. In the control condition graded stimulation of the baroreceptors caused a progressive lengthening in R–R interval, the maximal effect being + 477.4 ± 57.2 ms. Immersion increased the R–R interval from 774.2 ± 3.2 to 961.6 ± 5.8 ms (P < 0.01) and reduced mean arterial pressure (cuff measurement) from 96.0 ± 1.0 to 82.3 ± 0.9 mmHg. The changes in R–R interval induced by carotid baroreceptor stimulation were virtually identical with those observed in the absence of immersion. However, owing to the lower baseline heart rate during immersion, this meant a lesser degree of reflex bradycardia to carotid baroreceptor stimulation (maximal reduction − 30.5 ± 3.0 beats/min and −19.3 ± 3.1 beats/min before and during immersion respectively).

4. Thus, although the baroreflex sensitivity as expressed by changes in R–R interval is altered, the arterial baroreceptor ability to modulate heart rate (and perhaps cardiac output) is reduced when cardiopulmonary receptor activity is markedly increased. This may have implications in a number of physiological and pathophysiological settings.
Effects of verapamil and converting enzyme inhibition on bilateral renal function of two-kidney, one-clip hypertensive rats
Authors: Ploth David W. , Kleeman Kurt , Morrill Linell , Rademacher Ricardo , Jackson Cynthia A.
Published: August 2015

1. Experiments were conducted in two-kidney, one-clip renal vascular hypertensive rats (GHR) to assess the responses of each kidney to acute treatment with the antihypertensive calcium channel blocking agent verapamil in the presence and in the absence of converting enzyme inhibitor (CEI). One group of GHR (0.2 mm inner diam. clip 3 weeks before study) were examined during a control period, and during a second period of infusion of verapamil (600 μg h−1 kg−1). A second group of GHR were examined during a control period, during CEI (teprotide, 3 mg h−1 kg−1) infusion and during a third period of verapamil (600 μg h−1 kg−1) infusion superimposed on CEI infusion.

2. Although systemic blood pressure (BP) decreased from 175 ± 4 to 149 ± 5 mmHg (mean ± SEM) in response to verapamil alone, renal blood flow for non-clipped kidneys increased from 5.9 ± 0.4 to 6.5 ± 0.3 ml/min, indicating a 30% reduction of renal vascular resistance (P values 0.01; n = 9). Glomerular filtration rate (GFR) for non-clipped kidneys (n = 24) increased from 0.91 ± 0.09 to 1.47 ± 0.14 ml/min and filtration fraction increased from 0.32 ± 0.04 to 0.47 ± 0.03 (P values 0.05). Urine flow rate and absolute and fractional sodium excretion for non-clipped kidneys increased. GFR for clipped kidneys decreased during verapamil.

3. Treatment with CEI alone resulted in nearly identical responses of BP and function of the non-clipped kidney, except filtration fraction was unchanged. The addition of verapamil to ongoing converting enzyme blockade tended to augment the increased GFR of the non-clipped kidney.

4. Plasma renin activity (PRA) increased from 30 ± 3 to 59 ± 7 ng of angiotensin (ANG) I h−1 ml−1 with verapamil alone, a significantly larger increment than the increase of PRA from 27 ± 5 to 39 ± 9 ng of ANG I h−1 ml−1 in GHR subjected to comparable blood pressure reduction by mechanical aortic constriction.

5. Verapamil resulted in many similar effects on renal function to those observed during blockade of converting enzyme. The increased filtration fraction observed in response to verapamil may be the result of vasodilatation of the afferent arteriole or of an increase in the glomerular ultrafiltration coefficient.
Influence of cyclo-oxygenase inhibition and of leukotriene receptor blockade on pulmonary vascular pressure/cardiac index relationships in hyperoxic and in hypoxic dogs
Authors: Leeman Marc , Naeije Robert , Lejeune Philippe , Melot Christian
Published: August 2015

1. Overall mean pulmonary arterial pressure (MPAP)/cardiac index (CI) relationships were investigated in 13 pentobarbital anaesthetized dogs ventilated consecutively with a fraction of inspired O2 (F1o2) of 0.4 and with a F1o2 of 0.1. This sequence of alternated F1o2 0.4 and F1o2 0.1 was repeated (1) in the dogs with a strong pulmonary pressor response to hypoxia (more than 20% increase in pulmonary vascular resistance) (n = 6) under a continuous infusion of the leukotriene receptor blocker FPL 57231 (2 mg min−1 kg−1), and (2) in the dogs with a weak pressor response to hypoxia (n = 7) after cyclo-oxygenase inhibition by acetylsalicylic acid (1 g intravenously). Five-point MPAP/CI plots were constructed by opening a femoral arteriovenous fistula or by stepwise inflations of an inferior vena cava balloon catheter. The MPAP/CI plots were rectilinear in all experimental conditions.

2. In responders, hypoxia was associated with an increase in MPAP over the entire range of CI studied (1–5 litres min−1 m−2). Infusion of FLP 57231 abolished the vasoconstricting effect of hypoxia.

3. In non-responders, MPAP was not affected by hypoxia over the entire range of CI. After acetylsalicylic acid administration, hypoxia resulted in a significant rise in MPAP from 2 to 5 litres min−1 m−2.

4. Infusion of FLP 57231 decreased mean systemic arterial pressure at both F1o2 0.4 and F1o2 0.1, while acetylsalicylic acid had no effect on systemic haemodynamics.

5. Stability of pulmonary vascular tone at F1o2 0.4 and at F1o2 0.1 and reproducibility of the hypoxic pressor response was ascertained in an additional group of five dogs with CI kept constant and MPAP measurements every 6 min during four consecutive periods of 30 min (i.e. maximum time needed to generate a MPAP/CI plot) alternately at F1o2 0.4 and at F1o2 0.1.

6. These results suggest that pulmonary vascular reactivity to hypoxia is regulated by balanced actions of vasoconstricting leukotrienes and vasodilating prostaglandins in anaesthetized dogs. They also indicate a vasodilating effect of FPL 57231 on systemic vessels.
Corticosteroid binding globulin in normotensive and hypertensive human pregnancy
Authors: Potter Julia M. , Mueller Utz W. , Hickman Peter E. , Michael Con A.
Published: August 2015

1. Corticosteroid binding globulin (CBG) concentrations in maternal plasma have been measured throughout pregnancy in a series of 100 singleton pregnancies in 89 normotensive women. Plasma CBG concentrations were monitored also in 10 women with essential or renovascular hypertension. Plasma albumin, Cortisol and oestriol were measured concurrently.

2. Plasma CBG increased two and a half to three times during pregnancy. In those women who developed hypertension in pregnancy (mean arterial pressure > 107 mmHg), the plasma CBG concentrations were significantly lower than in those who remained normotensive. In women who developed hypertension, the CBG either failed to increase at the same rate as in normal pregnancies or the level fell before the appearance of hypertension. The earlier the onset of hypertension, the greater the decline in CBG. In all subjects, the CBG concentration at 34–36 weeks gestation was directly related to the birthweight of the infant.

3. Plasma Cortisol levels were depressed in hypertension relative to that in the normotensive women. Whilst plasma albumin levels decreased at least 30% in most women during pregnancy, the fall tended to be less in hypertensive women, but there was marked overlap between patient groups. Plasma oestriol concentrations were depressed only in the very severely affected cases.

4. It is suggested the CBG concentration is a further reflection of the metabolic abnormalities associated with hypertension in pregnancy, and that it can be used as a marker to identify and monitor those patients at risk.
Elastase inhibitors in sputum from bronchitic patients with and without α1-proteinase inhibitor deficiency: partial characterization of a hitherto unquantified inhibitor of neutrophil elastase
Authors: Morrison H. M. , Kramps J. A. , Afford S. C. , Burnett D. , Dijkman J. H. , Stockley R. A.
Published: August 2015

1. Anti-elastase function in sputum sol-phase from patients with α1-proteinase inhibitor (α1PI) deficiency was compared with sol-phase from patients with cigarette smoke-induced bronchitis and emphysema.

2. Both α1PI (2P < 0.01) and anti-leucoprotease (ALP) (2P < 0.01) concentrations were lower in sol-phase from the α1PI-deficient group, although α2-macroglobulin (α2M) levels were similar.

3. There was no difference in α1PI function between the two groups, but the inhibitor was only ≃ 30% active.

4. The absolute neutrophil elastase (NE) inhibitory capacity was similar in both groups (median 185 μg of NE inhibited/ml of sputum, range 80–480, for the α1PI-deficient group; median 175, range 80–300, for the bronchitic group). A substantial proportion of NE inhibition in secretions could not be accounted for by the amount of α1PI, ALP and α2M present (median 74.8%, range 43.2–97.4, for α1PI-deficient sol-phase; median 50.0%, range 0–80.8, for bronchitic sol-phase).

5. Gel filtration of sol-phase demonstrated the presence of NE inhibition in the low molecular weight fractions which was markedly sensitive to changes in substrate concentration and ionic strength, in contrast to purified α1PI and ALP.

6. Sputum sol-phase from both groups failed to prevent hydrolysis of elastin–fluorescein or succinyltrialanyl-p-nitroanilide by NE completely during prolonged incubation in the presence of an excess of functional inhibitors. This was more apparent in secretions from subjects with α1PI deficiency and may explain why such patients have a more rapidly progressive form of emphysema.
Erythrocyte phosphoinositide metabolism in essential hypertensive patients and their normotensive offspring
Authors: Riozzi A. , Heagerty A. M. , Ollerenshaw J. D. , Swales J. D.
Published: August 2015

1. The metabolism of phosphoinositides was investigated in erythrocyte membranes of essential hypertensive patients, normotensive offspring of hypertensive patients and matched controls.

2. Measurement of 32P-labelling of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bis-phosphate revealed no differences in the rate of incorporation of the isotope in essential hypertensive patients compared with controls.

3. In the normotensive offspring of essential hypertensive patients there was a highly significant increase in the rate of 32P incorporation (P < 0.01), compared with matched controls, indicating a higher rate of metabolic turnover in these subjects.

4. These data demonstrate that phosphoinositide metabolism is enhanced in subjects genetically at risk of hypertension, before the blood pressure has risen, but once the blood pressure is established, it is no different from control values. Abnormal phosphoinositide metabolism may be a further manifestation of a genetically determined defect of membrane physicochemical function underlying essential hypertension.
Effect of different levels of protein intake on renal deterioration and nutritional state in experimental renal disease
Authors: Okuda Seiya , Motomura Kenichi , Sanai Tohru , Hirakata Hideki , Nanishi Fumio , Onoyama Kaotu , Fujishima Masatoshi
Published: August 2015

1. We examined the effects of various levels of dietary protein on the course of adriamycin-induced nephropathy in rats fed with high (30%), intermediately low (10%) or strictly low (5%) protein diets for 24 weeks.

2. In the rats fed on the 30% protein diets, there were massive proteinuria, progressive increases in serum creatinine and focal glomerular sclerosis associated with severe tubulo-interstitial changes.

3. With the 5% dietary protein, proteinuria was decreased, the levels of serum creatinine were preserved within normal ranges and renal histological changes diminished. Weight loss and hypoproteinaemia were more marked.

4. With intermediate protein restriction (10% protein), renal function and plasma protein were preserved but body weight did not increase normally.

5. Aggregated human immunoglobulin G, which had been intravenously injected at weeks 12 and 24, accumulated in the glomeruli more densely in rats fed on the 30% protein diet than in those fed on the 10% or 5% protein diets.

6. We tentatively conclude that functional and histological deterioration of focal glomerular sclerosis can be prevented by appropriate restriction of dietary protein; however, severe protein restriction does aggravate nutritional states.
A comparison of the structural integrity of several commonly used preparations of rat small intestine in vitro
Authors: Plumb Jane A. , Burston David , Baker Terry G. , Gardner Michael L. G.
Published: August 2015

1. The structural integrities of various preparations of rat small intestine for the study of absorption in vitro have been compared after incubation or perfusion.

2. Perfused intestines removed from anaesthetized rats, and thus never deprived of a supply of oxygen, maintain their structural integrity even after perfusion for 1 h provided that a Krebs–Henseleit bicarbonate perfusate is used. However, intestines removed from freshly killed rats show severe villus disruption and oedema after perfusion for only 20 min.

3. Extensive damage to both crypts and villi is observed in everted sacs of small intestine incubated for 20 min, regardless of the buffer system used. Intestinal rings show damage at the tips of the villi after incubation for 2 min, but otherwise remain morphologically intact; this damage is progressive with time.

4. It is concluded that the exact mode of preparation of intestinal tissue is critical for preservation of structural and functional integrity and that this is especially important in quantitative studies on transport processes. Further, it is recommended that routine monitoring of the integrity of intestinal preparations in vitro is desirable and that histological assessment is an appropriate technique.
The effect of indomethacin on the response of protein synthesis to feeding in rats and man
Authors: McNurlan M. A. , McHardy K. C. , Broom J. , Milne E. , Fearns L. M. , Reeds P. J. , Garlick P. J.
Published: August 2015

1. Protein synthesis was measured in muscle of fed and fasted rats. Synthesis rates were 29% higher with feeding. Treatment with indomethacin before feeding completely blocked the stimulation of protein synthesis.

2. Whole-body protein synthesis was measured in six healthy volunteers with [15N]glycine in fasted and fed states. Feeding increased synthesis rates by 50%. An oral dose of indomethacin 2 h before the measurement of protein synthesis had no effect in either the fasted or fed state.
Does dopamine regulate aldosterone secretion in the rat?
Authors: Inglis G. C. , Kenyon C. J. , Hannah J. A. M. , Connell J. M. C. , Ball S. G.
Published: August 2015

1. This study investigated the role of dopamine in the control of adrenal steroidogenesis. Adrenaline, noradrenaline and dopamine have been measured in plasma and in the adrenal zona glomerulosa and medulla of rats fed low, normal and high sodium diets and in zona glomerulosa tissue of rats with adrenal regeneration hypertension (ARH).

2. Adrenal concentrations (means ± se) of adrenaline, noradrenaline and dopamine in rats fed a normal diet were 1471 ± 335, 527 ± 75 and 51 ± 12 nmol/g in the medulla, and 66 ± 17, 18 ± 9 and 6 ± 1 nmol/g in the zona glomerulosa. The dopamine content of the zona glomerulosa was greater than could be accounted for by simple contamination from the medullary catecholamines and is commensurate with that of tissue with dopaminergic innervation.

3. Adrenal noradrenaline and adrenaline concentrations and plasma catecholamine and corticosterone concentrations were not affected by dietary sodium intake. Plasma aldosterone concentrations were > 3030.4, 339.8 ± 41.5 and 55.2 ± 11.0 pmol/l in rats fed low, normal and high sodium diets respectively.

4. Five weeks after right adrenalectomy and nephrectomy and left adrenal enucleation, ARH rat systolic blood pressure had increased by 47 mmHg. In the regenerated gland, the concentrations of noradrenaline and adrenaline were negligible but dopamine was present in amounts similar to that of a normal adrenal cortex.

5. Dopamine is present in the adrenal zona glomerulosa in significant amounts but does not decrease when dietary sodium intake is reduced and is not inversely related to aldosterone secretion. These observations are compatible with findings in vivo which indicate that dopamine inhibits aldosterone secretion by an extra-adrenal process involving increased clearance of the major aldosterone trophin angiotensin II.
Platelet catecholamines and platelet function in normal human subjects
Authors: Wilson A. P. , Smith C. C. T. , Prichard B. N. C. , Betteridge D. J.
Published: August 2015

1. We have used high-performance liquid chromatography with electrochemical detection to measure plasma and platelet catecholamines in 24 normal subjects.

2. In the same subjects platelet function was assessed by measuring platelet aggregation in response to adenosine 5′-pyrophosphate, thrombin, adrenaline and collagen. Platelet sensitivity to prostacyclin was also examined.

3. Platelet noradrenaline showed a positive correlation with extent of aggregation induced by ‘low-dose’ collagen (1 μg/ml). No correlation was seen at the higher collagen concentration.

4. Platelet noradrenaline content also correlated with sensitivity of platelets to prostacyclin. High platelet noradrenaline concentrations appeared to result in decreased sensitivity to prostacyclin.

5. No other correlations were observed.

6. These data suggest that platelet noradrenaline rather than plasma levels may be involved in modifying platelet function in vivo. Local release of platelet catecholamines may affect the platelet/vessel wall interaction, the primary physiological step in platelet activation.
The effect of intravenous frusemide on urine dopamine in normal volunteers: Studies with indomethacin and carbidopa
Authors: Jeffrey R. F. , MacDonald T. M. , Rutter M. , Freestone S. , Brown J. , Samson R. R. , Lee M. R.
Published: August 2015

1. The urine dopamine response to intravenous frusemide (30 mg) was investigated in 15 salt replete male volunteers. The effects of oral indomethacin (100 mg) and oral carbidopa (100 mg) given before intravenous frusemide were studied in the same group of subjects.

2. Frusemide produced a significant increase in urine dopamine output within 15 min.

3. Indomethacin attenuated the natriuretic and renin responses to frusemide, but did not alter urine dopamine output.

4. Carbidopa lowered urine dopamine to undetectable levels, but did not significantly affect the natriuretic and renin responses to frusemide.

5. We conclude that urine dopamine excretion after frusemide is not directly related to increased sodium excretion or renin response and it is not mediated by the prostaglandins. In addition, dopamine does not contribute to the renal actions of frusemide under normal conditions.
Fatty acid synthesis and triacylglycerol accumulation in rat liver after chronic ethanol consumption
Authors: Venkatesan S. , Ward R. J. , Peters T. J.
Published: August 2015

1. Liver slices from chronically alcohol-fed rats incubated with 3H2O showed less than half the fatty acid synthesis rates of pair-fed controls. Addition of 50 mmol/l ethanol or of 10 mmol/l lactate and 1 mmol/l pyruvate to the incubation medium did not alter the fatty acid synthesis rates in either groups. Hepatic fatty acid synthesis rates measured in vivo with 3H2O were also significantly reduced in alcohol-fed rats.

2. Time-course experiments showed that after 1 week on the ethanol diet hepatic fatty acid synthesis rates in vitro were similar to control rats, although the liver triacylglycerol content was significantly increased. From the second week of feeding, fatty acid synthesis rates were significantly lower in alcohol-fed rats and the liver triacylglycerol content progressively increased compared with controls.

3. Fatty acid synthase activity in liver cytosolic fractions were similar to controls in the alcohol-fed group after 1 week of feeding but were significantly lower in alcohol-fed rats from the second week onwards.

4. These results indicate that hepatic triacylglycerol accumulation after alcohol feeding is not due to increased fatty acid synthesis. The reduced fatty acid synthesis observed is a consequence of triacylglycerol accumulation.
Renal response to vasopressin and indomethacin in cisplatin-treated rats
Authors: Lote Christopher J. , Harpur Ernest S. , Thewles Andrew , Phipps Donna J.
Published: August 2015

1. Cisplatin [6 mg/kg body weight, in 0.9% (w/v) NaCl] was injected intraperitoneally as a single dose to two groups of rats (Fischer 344 strain). Two further groups of rats, injected intraperitoneally with an equivalent volume of 0.9% (w/v) NaCl, were used as controls. The cisplatin-treated rats developed a pronounced polyuria which did not recover during an 18 week observation period.

2. After 21 weeks, one group of the cisplatin-treated animals received a 6 h infusion of 2.5% d-glucose. Vasopressin (60 μ-units min−1 100 g−1 body weight) was incorporated into the infusate for the final 2 h. A control group of animals received an identical infusion. One week later the other group of cisplatin-treated rats received a 6 h infusion of 0.9% (w/v) NaCl. Indomethacin was incorporated into the infusate for 15 min, at 3 h 52.5 min, to deliver a dose of 10 mg/kg body weight. A control group again received an identical infusion.

3. Cisplatin did not impair the antidiuretic effect of vasopressin, but it reduced the natriuretic effect of vasopressin, and also impaired the ability of the animals to produce concentrated urine.

4. Cisplatin did not alter basal PGE2 excretion, or the reduction in PGE2 excretion induced by indomethacin. However, the urine flow in the cisplatin-treated group did not fall after indomethacin, whereas there was a fall in urine flow in the control group.
Tubular prostaglandin E2 production and its role in urinary hypotonicity after release of ureteral occlusion in the rat
Authors: Torikai Shozo
Published: August 2015

1. In order to explore the involvement of endogenous prostaglandin E2 (PGE2) in the urine concentration defect after ureteral occlusion, PGE2 production by isolated collecting ducts in vitro and effects of indomethacin on urine osmolality in vivo were examined.

2. Twenty-four hours ureter obstruction caused increased PGE2 production by the medullary collecting ducts, which was maintained at a high level on the day after release of obstruction (0.8 ± 0.2 pg/mm normal, 8.1 ± 0.9 pg/mm 24 h obstruction, and 6.6 ± 1.0 pg/mm post-obstruction, mean ± sem). An enhanced PGE2 production was also observed for papillary collecting duct on the day after release of 24 h ureteral occlusion (3.9 ± 0.5 pg/mm normal and 7.7 ± 1.2 pg/mm post-obstruction).

3. Administration of indomethacin to the unilateral post-obstructive rats slightly raised the urine osmolality of the post-obstructed kidney (from 339 ± 17 to 390 ± 22 mosmol/kg H2O), while it had a greater effect on the contralateral intact kidney (from 1569 ± 138 to 2567 ± 198 mosmol/kg H2O).

4. Our data may indicate that the urine concentration defect after 24 h ureteral occlusion is ascribable mainly to a mechanism other than increased endogenous PGE2.