bluuebunny/crossref_metadata_2025 huggingface dataset:
Leucine Uptake by Splanchnic and Leg Tissues in Man: Relative Independence of Insulin Levels
Authors: Eriksson Ljusk Siw , Hagenfeldt Lars , Felig Philip , Wahren John
Published: August 2015

1. The influence on leucine disposal of physiological alterations in plasma insulin concentrations was examined in three groups of healthy male subjects, six in each group. After an overnight fast the subjects received an intravenous infusion of either leucine (300 μmol/min for 150 min, series A), or leucine plus glucose (2.2 mmol/min, series B), or leucine, somatostatin (7 μg/min) and glucagon (1 ng/min, series C). Arterial concentrations of substrates and their net exchange across the splanchnic and leg tissues were determined with a catheter technique.

2. Insulin concentrations rose from 12 ± 2 to 20–22 μ-units/ml in series A, from 11 ± 3 to 60–65 μ-units/ml in series B and decreased from 8 ± 1 to approximately 5 μ-units/ml in series C.

3. The basal leucine concentration for all subjects was 109 ± 8 μmol/l and it rose progressively during the infusions. In series A, the level was 598 ±20 μmol/l after 150 min. The corresponding value was 542 ±38 μmol/l in series B and 651 ±25 μmol/l in series C. Significant differences were observed between series A and B (P < 0.05) and series A and C (P < 0.01) when data for 90–150 min of infusion were combined (analysis of variance).

4. In all groups the leucine infusion resulted in an augmented net uptake of leucine across the leg (77-85 μmol/min) and across the splanchnic bed (61-72 μmol/min) but no significant inter-group differences were observed.

5. From these findings we conclude that insulin accelerates and hypoinsulinaemia slows the disposal of an exogenous load of leucine. These effects of insulin result in only modest differences in arterial leucine concentrations and in no demonstrable changes in peripheral or splanchnic leucine exchange, suggesting that insulin plays only a minor role in the disposal of leucine.
Urinary Coproporphyrin in Lead Intoxication: A Study in the Rabbit
Authors: Henderson M. J. , Toothill C.
Published: August 2015

1. Lead acetate was administered to adult New Zealand White rabbits in their drinking water. Their mean blood lead level rose to 4.5 μmol/l within a week and then remained relatively constant.

2. The rabbits developed a marked coproporphyrinuria. Plasma levels of coproporphyrin increased but not in proportion to the urine excretion. Thus the renal clearance of coproporphyrin rose from a mean of 1.8 ml/min to 32.2 ml/min whilst creatinine clearance remained constant.

3. The concentration of coproporphyrin in renal venous blood from control rabbits was found to be slightly lower than that in arterial blood. In the lead intoxicated rabbits the concentration of coproporphyrin in renal venous blood was approximately three times higher than the arterial concentration.

4. Significantly higher levels of lead, porphobilinogen, uroporphyrin, coproporphyrin and protoporphyrin were found in renal tissue than in brain, heart or liver.

5. Renal tissue homogenates from control rabbits were able to synthesize porphobilinogen, uroporphyrin, coproporphyrin and protoporphyrin when incubated with 5-aminolaevulinic acid. Renal tissue from lead intoxicated rabbits was also able to synthesize these haem precursors although at a reduced rate.

6. Three enzymes from the haem biosynthetic pathway were assayed in renal mitochondria. Compared with those from controls, mitochondria from lead intoxicated rabbits showed no significant difference in ferrochelatase activities, but the activities of coproporphyrinogen oxidase were decreased, and those of 5-aminolaevulinate synthase were increased.

7. It was concluded that a large portion of the excess coproporphyrin excreted by the lead intoxicated rabbits was of renal origin.
Study of the Electrophysiological Effects of Early or Subendocardial Ischaemia with Intracavitary Electrodes in the Dog
Authors: Donaldson R. M. , Taggart P. , Nashat F. , Abed J. , Rickards A. F. , Noble D.
Published: August 2015

1. The early electrophysiological patterns of regional subendocardial ischaemia were studied by using the paced endocardial evoked response and simultaneous endocardial monophasic action potential recordings in 16 experiments in open chested dogs. Ischaemia was produced by transient (1-3 min) coronary artery occlusion.

2. Regional subendocardial isochaemia caused asynchronous activation due to differential conduction delay and shortened repolarization as evaluated by the duration of the paced evoked response from 175±(sd) 18.7 ms to 167 ± 16 ms (P <0.001). These changes occurred within 60 s of occlusion and reversed rapidly after release of the occlusion.

3. In simultaneous endocardial monophasic action potentials there was a decrease in plateau amplitude and the duration of repolarization shortened from 180±(sd) 21.2 ms to 167 ±20.4 ms (P <0.001).

4. The delay in endocardial activation after 2 min ischaemia was 5.5 ms, which is considerably shorter than the conduction delay previously reported in the subepicardial layers.

5. The calcium-channel blocking drug verapamil (infused at 0.4 mg/kg) altered the rate at which shortening of repolarization and asynchronous activation occurred during ischaemia in six experiments.

6. These experiments suggest that intracavitary electrodes could provide earlier and more sensitive detection of regional subendocardial ischaemia and may permit the assessment of therapy on the early electrical changes in the intact heart.
The Effects of Captopril on Blood Pressure, Urinary Water and Electrolyte Excretion and Drinking Behaviour in Brattleboro Rats
Authors: Gardiner Sheila M. , Bennett T.
Published: August 2015

1. The effects of the orally active converting enzyme inhibitor, captopril (SQ 14225), on blood pressures and intakes and urine outputs of water and electrolytes were studied in rats with hereditary hypothalamic diabetes insipidus (Brattleboro strain) and in Long Evans rats (parent strain).

2. Captopril given in the drinking water (30 mg day−1 kg−1) caused an increase in fluid intake and urine output in both strains of rat; the difference between intake and measured output did not change.

3. Captopril caused a significant natriuresis wnen given to animals in the non-steady state but did not significantly affect the urinary electrolyte excretion of animals in a steady state; in the latter group, however, captopril caused a significant reduction in food intake. Hence, under both conditions, captopril caused a reduction in sodium balance.

4. Systolic blood pressures were reduced by captopril (given in the drinking water) in Long Evans rats and in Brattleboro rats; there was no accompanying change in heart rate.

5. Bolus administration of captopril (30 mg day−1 kg−1) either intragastrically or subcutaneously did not change the fluid intakes or outputs in either strain of rat.

6. In a separate experiment, rats were given the choice to drink water or a captopril solution. The results showed that the increased fluid intake in response to captopril was not due to a liking for the taste of the solution.

7. The dipsogenic response to captopril may have been due to the fall in blood pressure which occurred, leading to renin release and a peripheral build-up of angiotensin I, which was converted into angiotensin II in the central nervous system. The possibility that the same dose given as a bolus may have inhibited central, as well as peripheral, converting enzyme activity is discussed.
Importance of Platelet-Free Preparations for Evaluating Lymphocyte Nucleotide Levels in Inherited or Acquired Immunodeficiency Syndromes
Authors: Goday A. , Simmonds H. A. , Webster D. R. , Levinsky R. J. , Watson A. R. , Hoffbrand A. V.
Published: August 2015

1. Low ATP/ADP ratios have been reported consistently for nucleotide levels of mononuclear cells separated from peripheral blood by conventional techniques.

2. We have established that these low values (mean 2.3:1) were not due to cell damage or poor viability, but resulted from heavy platelet contamination, which is unavoidable when heparinized blood is used. The results reflect the low ATP/ADP ratios (mean 1.6:1) characteristic of platelets. Platelet-free extracts from defibrinated blood had very high ATP/ADP ratios (mean 17.4:1).

3. The initial finding of detectable amounts of deoxy-ATP and deoxy-GTP in mononuclear cells from children with two distinct inherited immunodeficiency disorders [adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) deficiency respectively] many have been due to contamination by nucleated erythrocytes as well as platelets in non-defibrinated preparations.

4. Defibrination before nucleotide extraction of mononuclear cells from a patient with T-cell leukaemic/lymphoma treated with the ADA inhibitor deoxycoformycin enabled the demonstration of grossly raised deoxy-ATP levels relative to deoxy-ADP levels (ratio 16.1:1), associated with severe ATP depletion. This reciprocal relationship between ATP and dATP was found by us previously in the erythrocytes in inherited ADA deficiency.

5. These findings underline the importance of extracts uncontaminated by platelets, or nucleated erythrocytes, in the evaluation of lymphocyte nucleotide levels in inherited or acquired immunodeficiency syndromes.
Effect of Adrenergic and Vagal Blockade on the Normal Human Airway Response to Exercise
Authors: Warren J. B. , Jennings S. J. , Clark T. J. H.
Published: August 2015

1. Ten normal, non-asthmatic subjects performed an 18 min graduated exercise test on a static exercise bicycle on 3 separate days. They received either no medication, or propranolol 80 mg orally 2 h before, or ipratropium bromide 0.216 mg by inhalation 30 min before, the start of exercise.

2. With no medication, transpulmonary index (TPI), a measure of airway resistance, fell linearly during exercise from a resting value of 0.269 ± 0.024 to 0.170 ± 0.014 kPa·1−1·s by the end of exercise. This returned to baseline between 2 and 4 min after stopping exercise.

3. Propranolol elevated baseline TPI slightly from 0.270 ± 0.024 to 0.294 ± 0.024 before exercise and during exercise this fell linearly to 0.185 ± 0.016 kPa·1−1·s. The fall in TPI during exercise after propranolol was not significantly different from the fall seen with no medication. Six minutes after exercise stopped TPI rose to 0.336 ± 0.035 kPa·1−1·s after propranolol. All values for TPI from 4 min to 16 min after exercise were significantly higher after propranolol than the corresponding values found after no medication (P<0.05).

4. Ipratropium bromide decreased baseline TPI from 0.264 ± 0.024 to 0.163 ± 0.013 kPa·1−1·s (P<0.001) and this did not change significantly further either during or after exercise.

5. Normal subjects show considerable airway dilatation during exercise and this appears to result from inhibition of resting vagal tone. The sympathetic system does not appear to mediate the airway dilatation during exercise, but it may be important in protecting against post-exercise bronchoconstriction.
Calcium Malabsorption in Elderly Women with Vertebral Fractures: Evidence for Resistance to the Action of Vitamin D Metabolites on the Bowel
Authors: Francis R. M. , Peacock M. , Taylor G. A. , Storer J. H. , Nordin B. E. C.
Published: August 2015

1. Radio-calcium absorption, plasma 25-hydroxyvitamin D [25-(OH)D] and 1,25-dihydroxyvitamin D [1,25-(OH)2D] concentrations were measured in 19 elderly women with, and 21 without, vertebral fractures, before and after treatment with 25-hydroxyvitamin D3 [25-(OH)D3], to establish whether malabsorption of calcium in elderly women with vertebral fractures has a cause different from that in elderly women without vertebral fractures.

2. Malabsorption of calcium and low plasma 25-(OH)D and 1,25-(OH)2D concentrations were common in both groups of women but there was no significant difference in these variables between the two groups.

3. After treatment with 40 μg of 25-(OH)D3 daily for 7 days, there was a significant increase in plasma 25-(OH)D and 1,25-(OH)2D in both groups of women, but radio-calcium absorption increased significantly only in the group without vertebral fractures.

4. Elderly women with vertebral fractures have malabsorption of calcium which is resistant to the action of vitamin D metabolites at concentrations which correct calcium malabsorption in elderly women without vertebral fractures.
Prostaglandins Cause An Increase in Serum Acute-Phase Proteins in Man, Which is Diminished in Systemic Sclerosis
Authors: Whicher J. T. , Bell A. M. , Martin M. F. R. , Marshall L. A. , Dieppe P. A.
Published: August 2015

1. The prostaglandin E1 increases the plasma concentration of acute-phase proteins in man and decreases the concentration of certain carrier proteins.

2. This response is greatly diminished in patients with systemic sclerosis, a chronic inflammatory disease leading to fibrosis.

3. These findings pose new questions about the mediation of the acute-phase response and its role in controlling the inflammatory process.
Baroreflex Setting and Sensitivity after Acute and Chronic Nicardipine Therapy
Authors: Young M. A. , Watson R. D. S. , Littler W. A.
Published: August 2015

1. Intra-arterial pressure, baroreflex sensitivity and the baroreflex set point were measured in eight patients with essential hypertension during a control period and then after acute treatment (2 h after a 30 mg oral dose) and after chronic treatment (at least 2 months) with nicardipine hydrochloride, a calcium channel antagonist.

2. Mean intra-arterial blood pressure fell after the acute treatment from 130 ± 14 (sd) control to 118 ± 11 mmHg, P<0.05, and after chronic treatment to 112 ± 19 mmHg, P<0.05. Heart rate increased from 72 ± 11 control to 81 ± 16 beats/min, P<0.05, during acute treatment indicating activation of the baroreflex control mechanism, but returned to control values with chronic treatment (72 ± 11 control vs 69 ± 9 beats/min chronic), indicating a significant shift to the left of the baroreflex set point. There was no change in baroreflex sensitivity after either acute or chronic treatment (control 4.7, acute 4.3, chronic 5.1 ms/mmHg, P not significant for all values).

3. Nicardipine significantly reduces mean intraarterial pressure both acutely and chronically; the latter is associated with a return of the heart rate to control values due to resetting of the baroreflex control mechanism.
Captopril Enhances Vascular and Adrenal Responsiveness to Angiotensin II in Essential Hypertension
Authors: Koletsky Richard J. , Gordon Murray B. , Leboff Meryl S. , Moore Thomas J. , Dluhy Robert G. , Hollenberg Norman K. , Williams Gordon H.
Published: August 2015

1. The converting-enzyme inhibitor captopril (25–50 mg orally every 6 h for 66 h) was used to dissociate the circulating levels of angiotensin II (ANG II) from changes in sodium balance in 11 patients with normal renin essential hypertension on 10 mmol of sodium/day intake. Pressor, renal vascular and adrenal responses to graded infusions of ANG II (0.3, 1 and 3 pmol kg−1 min−1) were measured before and after captopril administration. Systemic vascular responses were assessed by measuring diastolic blood presusre (DBP), renovascular responses by measuring p-aminohippurate (PAH) clearance and adrenal responses by measuring plasma aldosterone.

2. After receiving captopril for 66 h the hypertensive subjects showed a significantly (P<0.004) enhanced blood pressure response to the infused ANG II but not to noradrenaline when compared with the response before captopril. ANG II (3 pmol kg−1 min−1) also produced a significantly (P<0.03) greater reduction in PAH clearance after (−194 ± 40 ml/min) compared with before (−104 ± 15 ml/min) captopril. These results suggest that the responsiveness to ANG II in these two target tissues is determined by the circulating ANG II level.

3. In the adrenal gland the aldosterone responses to ANG II also were significantly greater after (P < 0.01) than before captopril (increment at 3 pmol kg−1 min−1: 660 ± 88 vs 381 ± 94 pmol/l). These results are in distinct contrast with the responses previously reported for normotensive subjects and support the hypothesis that the regulation of aldosterone secretion is altered in subjects with essential hypertension.
A Passive Sodium Transport Inhibitory Factor (Inhibitin) Released from Leukaemic Promyelocytes in Culture
Authors: Morgan Kevin , Mir M. Afzal
Published: August 2015

1. Previous studies have shown that myeloid leukaemic blast cells contain a heat stable factor which inhibits bidirectional sodium transport in normal erythrocytes. This study was undertaken to establish whether leukaemic promyelocytes in culture secrete this factor.

2. Two cell-lines of leukaemic promyelocytes (HL-60 and JR) were grown and culture media from both reduced significantly the ouabain-insensitive sodium efflux rate constant, whereas conditioned culture medium (incubated like the cells in culture) had no inhibitory effect.

3. Promyelocyte extract reduced significantly (P < 0.01) the total sodium efflux rate constant from 0.393 ± 0.030 (sd) to 0.311 ± 0.060, and ouabain-insensitive efflux rate constant from 0.131 ± 0.008 to 0.079 ± 0.009 (P<0.001).

4. The inhibitory factor was heat stable (80°C for 30 min) and it inhibited sodium efflux through a pathway which was not inhibited by ouabain or frusemide.

5. These studies suggest that leukaemic promyelocytes secrete the previously identified passive sodium transport inhibitory factor.
The Effects of Platelet-Derived Contractile Agents on Human Digital Arteries
Authors: Moulds R. F. W. , Iwanov V. , Medcalf R. L.
Published: August 2015

1. The contractile responses of spiral strips of human digital arteries to samples of a suspension of human platelets aggregated by thrombin have been studied at different time intervals after aggregation.

2. Platelets added to the arterial strips 1 min after aggregation of the platelets produced contractile responses which were significantly greater than those produced by corresponding platelets added 20 min after aggregation.

3. When platelets were aggregated in the presence of indomethacin or the thromboxane synthetase antagonist 1-benzylimidazole, contractile responses produced by the platelets 1 min after aggregation were significantly reduced. They were then not significantly different from those produced by addition of the aliquots 20 min after aggregation, which were unaffected.

4. Pretreatment of the arteries with the serotonin antagonist ketanserin nearly abolished the contractile responses produced by addition of the platelets 20 min after aggregation, and significantly reduced those produced by addition of the platelets 1 min after aggregation.

5. Ketanserin did not affect the contractile responses of the arteries to potassium chloride, prostaglandin F2α, or the endoperoxide analogue U-46619, but antagonized the contractile effects of exogenous serotonin.

6. Combination of pretreatment of the arteries with ketanserin and aggregation of the platelets in indomethacin or 1-benzylimidazole virtually abolished contractile responses to platelets added both 1 min and 20 min after aggregation.

7. Tensions developed to different dilutions of platelets added 1 min after aggregation to arteries pretreated with ketanserin were not significantly different from those obtained to the same dilutions added 20 min after aggregation to arteries not pretreated with ketanserin.

8. It is concluded that there are two components to the contractile responses of human blood vessels produced by the aggregation of human platelets. One is labile, not produced when aggregation occurs in indomethacin or 1-benzylimidazole and is probably produced by thromboxane A2. The other is stable, markedly reduced by ketanserin, and probably produced by serotonin. Each of the components makes an approximately equal contribution to the contractures of human blood vessels produced by platelet aggregation.

9. It is also concluded that serotonin antagonists, in combination with a thromboxane synthetase inhibitor, may be of therapeutic benefit in clinical syndromes possibly mediated by platelet aggregation, such as cerebral transient ischaemic attacks and coronary spasm.
Effect of Unclipping on Pressor Responses in Rats with Renovascular Hypertension
Authors: Bing Robert F. , Swales John D. , Taverner David , Thurston Herbert
Published: August 2015

1. Pressor responses to angiotensin II and noradrenaline have been examined in two models of renovascular hypertension (two-kidney one-clip and one-kidney one-clip) before and 24 h after removal of the renal artery clip to examine the possible role of pressor hyper-responsiveness in the maintenance of hypertension. Early and chronic hypertension was studied to assess the part played by progressive structural hypertrophy.

2. Plasma renin concentration was elevated in early two-kidney hypertensive rats, whereas it was similar to that in age-matched normal rats in early one-kidney and chronic two-kidney hypertensive rats. Twenty-four hours after unclipping plasma renin concentration was the same in all groups. Unclipping restored blood pressure to normal levels by 24 h, whereas sham-operated animals remained hypertensive.

3. Angiotensin II responses in both early and chronic two-kidney one-clip hypertensive rats were lower than in age-matched normal rats. In unclipped rats responses were similar to those in normals. One-kidney hypertensive rats had similar angiotensin II responses to normal rats and there was no change with unclipping. Blockade of endogenous angiotensin II production by converting enzyme inhibition resulted in similar angiotensin II responses in hypertensive and unclipped groups.

4. In normal rats, angiotensin II responses were inversely related to plasma renin concentration (r = −0.47, P<0.001). Angiotensin II responses in hypertensive and unclipped rats were found to show a similar relationship to plasma renin concentration as normal rats.

5. Noradrenaline responses in hypertensive rats were similar to those in age-matched normals and there was no significant change with unclipping. In normal rats there was no relationship between noradrenaline responses and plasma renin concentration (r = −0.11, P<0.5).

6. These results emphasize the importance of the activity of endogenous renin-angiotensin in determining angiotensin II responses in vivo. It is concluded that neither the maintenance of hypertension nor the fall in blood pressure produced by removal of the renal artery clip in renovascular hypertension is due to changes in responsiveness to angiotensin II.
Bilirubin Content and 4-Nitrophenol Glucuronosyltransferase Activity in Gunn Rat Liver
Authors: Celier Chantal , Foliot Armelle
Published: August 2015

1. The purpose of this study was to determine whether the hepatic content of bilirubin could influence liver 4-nitrophenolglucuronosyltransferase (4-NP-GT) in the Gunn rat.

2. In animals fed on a 45% lipid diet, compared with rats fed on a normal lipid diet (3%), the bilirubin content of the hepatic microsomal fraction decreased and the bilirubin/protein ratio was reduced. 4-NP-GT activities were comparable in both groups.

3. Administration of clofibrate to Gunn rats greatly enhanced the bilirubin content of liver microsomal fraction. Since this treatment raised the microsomal protein content, the bilirubin/protein ratio was not modified. No significant change in 4-NP-GT was noted.

4. After bilirubin perfusion in Gunn and Wistar rats, no change was observed in hepatic monooxygenase activities or in 4-NP-GT, although the bilirubin/protein ratio was dramatically increased in the microsomal fraction.

5. From these results the low activity of liver 4-NP-GT in Gunn rats does not seem directly related to the hepatic content of bilirubin.
Radionuclide Demonstration of Ventilatory Abnormalities in Mild Asthma
Authors: Agnew J. E. , Bateman J. R. M. , Pavia D. , Clarke S. W.
Published: August 2015

1. The distribution of 5 μm 99mTc aerosol particles deposited in the lungs was compared with that of 81mKr gas in 20 asthmatic subjects (FEV1.0≥75% predicted) whose asthma was mild or in remission. Sixteen normal non-smokers and 14 ‘normal’ cigarette smokers were studied as control subjects.

2. Radioaerosol lung penetration in the ‘normal’ smokers was the same as in the normal non-smokers but was reduced in the asthmatic subjects.

3. Radioaerosol penetrated better than 81mKr to the lung apices of normal non-smokers and asthmatic subjects; it penetrated better than 81mKr to the lung bases of the asthmatic subjects.

4. Uneven distribution of aerosol relative to 81mKr related strongly to maximal mid-expiratory flow rate (MMFR) in the asthmatic subjects.

5. Aerosol deposition abnormalities in symptom-free asthmatic subjects may reflect basal airways closure at functional residual capacity and abnormal patterns of lung filling.
Exchangeable Sodium in Goldblatt One-Kidney One-Clip Hypertension in the Rat
Authors: McAreavey D. , Brown W. B. , Murray G. D. , Robertson J. I. S.
Published: August 2015

1. Exchangeable sodium (NaE), plasma active renin concentration and blood pressure were measured in rats with a sole remaining kidney before and after the development of hypertension induced by clipping of the single renal artery and again after unclipping.

2. Control observations were made in sham-clipped and sham-unclipped uninephrectomized rats.

3. Renal artery clipping caused hypertension and expansion of NaE, the latter being sustained throughout the 6 weeks during which the renal artery was constricted.

4. Hypertension in the clipped rats was progressive over 6 weeks, whereas the expansion of NaE was not; thus the two measurements were not significantly correlated.

5. Two rats which remained normotensive after clipping did not show expansion of NaE.

6. Plasma active renin was elevated in comparison with the sham-clipped controls on the day after clipping, but not thereafter.

7. Unclipping in hypertensive rats was followed by a return of NaE and blood pressure to control values.

8. Both the sustained expansion of NaE and the transient rise in active renin probably contribute to the development of hypertension in this model, but neither alone nor together do they provide a full satisfactory explanation.
Studies of Salivary Flow in Borderline Hypertension: Effects of Drugs Acting on Structures Innervated by the Autonomic Nervous System
Authors: Van Hooff M. , Van Baak M. A. , Schols M. , Rahn K. H.
Published: August 2015

1. Salivary flow and the influence of drugs on this were studied in subjects with borderline hypertension and in normotensive subjects.

2. Saliva production at rest was lower in borderline hypertensive subjects than in normotensive subjects. Plasma catecholamine levels were similar in both groups of subjects studied.

3. Intravenous injections of propranolol and phentolamine did not enhance saliva secretion in the borderline hypertensive group, whereas atropine caused the secretion to decrease in both groups. Intravenous infusions of neostigmine led to a dose-dependent increase of salivary flow. The dose-response curve for the stimulating effect of neostigmine on saliva production was shifted to the right in borderline hypertensive as compared with normotensive subjects.

4. The results of the study support the assumption that in subjects with borderline hypertension parasympathetic influence on the salivary glands is reduced.
Angiotensin II Binding to Human Mononuclear Cells: Receptor or Free Fluid Endocytosis?
Authors: Neyses L. , Locher R. , Wehling M. , Pech H. , Tenschert W. , Vetter W.
Published: August 2015

1. It has recently been claimed that there are angiotensin II (ANG II) receptors on human mononuclear cells and on platelets and this has been used for investigating the regulation of the renin-angiotensin system in hypertension. We here show the following.

2. Binding kinetics of 125I-labelled ANG II and [3H]ANG II to mononuclear cells were slow (maximum at 90 min) and the same as for [3H]-inulin.

3. As with [3H]inulin there was no binding at 4°C.

4. Release from the cells was slow and incomplete (about 30% after 15 min, 60% after 60 min).

5. Binding was not saturable over a range from 10−12 to 10−6 mol of ANG II/l, about 8% of offered peptide being bound at all concentrations.

6. Various inhibitors of free fluid endocytosis exhibited the same inhibition pattern of ANG II binding to mononuclear cells.

7. Therefore uptake of ANG II into mononuclear cells displayed all the features of free fluid endocytosis.

8. ANG II was degraded by carboxypeptidase A. When this degradation was prevented by d-phenylalanine, no binding occurred.

9. In platelet preparations contaminated by 0.3-5% of mononuclear cells, 125I-labelled ANG II was degraded as well. Free fluid endocytosis of the degradation product strongly depended on the percentage of contaminating mononuclear cells.

10. We conclude that there are no ANG II receptors on human mononuclear cells and that their presence on human platelets is doubtful.
Intracerebroventricular Infusion of Sodium Chloride-Rich Artificial Cerebrospinal Fluid in Rats Induces Natriuresis and Releases An Inhibitor of Prostaglandin Synthesis
Authors: Diez Javier , Colina Inmaculada , Guarner Francisco , Quiroga Jorge , Corzo Julio , Purroy Andrés , Prieto Jesús
Published: August 2015

1. Urinary sodium excretion in anaesthetized rats subjected to high-sodium artificial cerebrospinal fluid (CSF) infusion into the lateral brain ventricle, was significantly higher than in rats infused with normal-sodium CSF.

2. Urinary immunoreactive 6-ketoprostaglandin F1α, the stable derivative of prostacyclin, was significantly reduced in the high-sodium CSF group, as compared with the normal-sodium CSF group.

3. When dog aortic endothelium was incubated in the presence of plasma, endothelial prostacyclin production was found to be inhibited by plasma from rats infused with high-sodium CSF compared with the effect of plasma from the rats infused with normal-sodium CSF.

4. Our results indicate that intracerebroventricular infusion of high-sodium CSF induces a natriuretic response and is associated with the appearance of a humoral factor which blocks prostacyclin byosynthesis.
The influence of environmental temperature upon the thermoregulatory responses to ethanol in man
Authors: Fellows I. W. , MacDonald I. A. , Bennett T.
Published: August 2015

1. Ten healthy male subjects ingested ethanol (BP; 0.5 g/kg body weight) after an overnight fast, on two separate occasions, at environmental temperatures of either 21°C or 3O°C.

2. The mean maximal fall in deep body temperature was not significantly different on the two occasions, being 0.18°C and 0.17°C respectively.

3. Metabolic rates throughout the experiments at the two temperatures were not significantly different.

4. The vasodilatation of the hand and forearm vascular beds after ethanol ingestion was markedly reduced at the lower environmental temperature.

5. In three subjects who ingested a higher dose of ethanol (BP; 1.0 g/kg body weight) after an overnight fast, at an environmental temperature of 2l°C, the mean maximum fall in core temperature was 0.15°C, which was not significantly different from the change seen after consumption of the lower dose of ethanol.

6. It is likely that the failure of ethanol ingestion to provoke hypothermia at the lower environmental temperature was due to the attenuated vasodilatation observed under these conditions.
β-Adrenoceptors and Responsiveness in Cardiac Hypertrophy Associated with Renal Hypertension in Renovascular Hypertensive Rats
Authors: Ayobe M. Hani , Tarazi Robert C.
Published: August 2015

1. The possible contribution of changes in cardiac β-adrenoceptors to alterations in cardiac responses to isoprenaline were investigated in hearts isolated from rats with renovascular hypertension (two-kidney, one-clip Goldblatt), 6, 12 and 18 weeks after renal artery clipping. Cardiac responses were determined in vitro (Langendorff preparation), and ventricular β-adrenoceptors ([3H)dihydroalprenolol, [3H]DHA) were then assayed in the same 44 hearts.

2. There was no difference between renovascular hypertensive rats (RHR) and matched normotensive controls as regards chronotropic responses to isoprenaline or in atrial β-adrenoceptor numbers or apparent affinity.

3. Inotropic responses were significantly lower in all stages of RHR than in matched normotensive controls.

4. There was also a significant (P < 0.001) decrease in ventricular β-adrenoceptor density with no significant change in apparent affinity (Kd). Inotropic responsiveness to isoprenaline (max. increment in peak dP/dt) was significantly correlated with ventricular β-adrenoceptor density (r = 0.54, P = 0.0005).

5. These results suggest that the reduction of ventricular β-adrenoceptor density in that model of hypertension was responsible, at least partially, for the lowered inotropic responsiveness of the same hearts to isoprenaline.
Post-Exercise Reduction of Blood Pressure in Hypertensive Men is Not Due to Acute Impairment of Baroreflex Function
Authors: Bennett T. , Wilcox R. G. , MacDonald I. A.
Published: August 2015

1. Two experiments were carried out in male subjects. In the first experiment heart rate and blood pressures were measured before, during and for 90 min after a 50 min period of intermittent exercise in seven hypertensive subjects. After exercise there was a marked reduction in systolic and diastolic blood pressures; this effect lasted throughout the 90 min observation period and was unaccompanied by tachycardia.

2. In the second experiment heart rate and blood pressures were measured before and during the rest periods in a 50 min session of intermittent exercise in nine hypertensive and nine normotensive subjects. Following the first 10 min bout of exercise, resting blood pressures were significantly reduced in the hypertensive subjects; the reduction in blood pressure progressively increased following successive exercise periods. The normotensive subjects did not show a significant reduction in resting blood pressures until the fifth bout of exercise had been completed.

3. In the second experiment also, the competence of baroreflexes was assessed by measuring cardiovascular responses to lower body sub-atmospheric pressure (LBSP) 30 min before and 30 and 60 min after exercise. The post-exercise reduction in blood pressure was not due to exercise-induced impairment of baroreflex mechanisms since the reduced blood pressure after exercise was well maintained during lower body sub-atmospheric pressure. Furthermore, after exercise, exposure to lower body subatmospheric pressure elicited greater increases in heart rate and forearm vascular resistance than were seen before exercise.
A Micropuncture and Renal Clearance Study in the Rat of the Urinary Excretion of Heparin, Chondroitin Sulphate and Metabolic Breakdown Products of Connective Tissue Proteoglycans
Authors: Shum Daisy K. Y. , Baylis Christine , Scott John E.
Published: August 2015

1. Commercial heparin and acid glycosaminoglycans (AGAG) prepared from normal female human urine were tritiated catalytically in aqueous solution. Nasal septal chondroitin sulphate was tritiated by NaB3H4 reduction of the aldehydes produced by very limited periodate oxidation. The refined products were characterized by electrophoresis and biochemical analysis.

2. The tritiated products were infused into Munich-Wistar rats, and their kidney clearances were measured and compared with that of inulin.

3. The passage of heparin and chondroitin sulphate at the glomerulus was restricted, as shown by the ratios of their concentrations in Bowman's space fluid and plasma. Comparison with whole kidney urine/plasma ratios indicated that some tubular reabsorption also occurred. The low whole kidney clearance of AGAG from normal female human urine probably also resulted from restricted glomerular passage and tubular reabsorption.

4. The low whole kidney clearances, primarily caused by restricted transglomerular movement, are discussed on the bases of (a) the molecular sizes and shapes of the AGAG, (b) an electrostatic barrier at the basement membrane and (c) binding of AGAG to plasma colloids, thus reducing plasma levels of free AGAG.

5. The implications of these findings in (a) heparin therapy and (b) urinalysis of disorders of connective tissue metabolism are discussed.
The effects of Acute and Chronic β-Adrenoceptor Blockade on the Myofibrillar Contractile System in the Dog Heart
Authors: Davies M. K. , Cummins P. , Littler W. A.
Published: August 2015

1. Electrophoretic and enzyme techniques have been used to study the structure and function of the contractile protein system in the myocardium of dogs before and after β-adrenoceptor blockade. Animals were examined after acute β-adrenoceptor blockade by using intravenous atenolol (0.2 mg/kg) and following chronic therapy with oral atenolol (100 mg twice daily) for a mean period of 106 days.

2. Two-dimensional polyacrylamide-gel electrophoretic techniques were used to examine the myocardial contractile and regulatory proteins present in endomyocardial biopsy specimens obtained after acute and chronic β-adrenoceptor blockade. No differences in charge, molecular weight or the relative proportions of actin, myosin light chains, tropomyosin or troponin-C were seen after either acute or chronic β-adrenoceptor blockade.

3. The maximal activity and calcium sensitivity of the myofibrillar adenosine triphosphatase (ATPase) was also unchanged after acute and chronic atenolol therapy.

4. It is concluded that β-adrenoceptor blockade has no significant adaptive effect on the structural or functional properties of the myofibril.
Sex-Related Differences in Resting and Stimulated Plasma Noradrenaline and Adrenaline
Authors: Davidson L. , Vandongen R. , Rouse I. L. , Beilin L. J. , Tunney A.
Published: August 2015

1. Resting and stimulated plasma noradrenaline and adrenaline concentration were compared in 45 females and 45 males of similar age who did not smoke, drink alcohol or caffeine-containing beverages.

2. At rest plasma noradrenaline levels were consistently higher in females and adrenaline levels higher in males. These sex-related differences were maintained after isometric exercise, mental arithmetic and cold pressor testing.

3. Resting noradrenaline concentration was negatively correlated with Quetelet index in males and positively correlated with age in females.

4. These findings, based on precise catecholamine measurements under standardized conditions in subjects of similar age, reveal important sex-related differences which need to be taken into account in assessing sympatho-adrenal activity, particularly in relation to mechanisms in essential hypertension.
The Effects of a Chronic Infusion of Arginine Vasopressin in Salt-Restricted, Water-Deprived Man
Authors: Drew P. J. T. , Barnes J. N. , Holly J. M. P. , Knight A. , Goodwin F. J.
Published: August 2015

1. The effects of a 48 h infusion of arginine vasopressin (AVP) were measured in five separate studies on four normal salt-restricted physicians, in whom fluid retention was prevented.

2. The infusion was associated with an increase in renal sodium excretion which continued during the 24 h after the infusion had been discontinuted.

3. During the infusion plasma renin activity (PRA), plasma aldosterone and noradrenaline, and packed cell volume (PCV) fell; glomerular filtration rate, assessed by endogenous creatinine clearance, increased.

4. The findings are best explained by a vasopressin-induced increase in plasma volume, which in the absence of fluid retention is likely to have been due to a redistribution of body water.
Uptake and Metabolism of Thyroid Hormones by the Rat Foetus in Early Pregnancy
Authors: Woods R. J. , Sinha A. K. , Ekins R. P.
Published: August 2015

1. Pregnant rats were injected with trace amounts of [125I] thyroxine ([125I]T4) or [125I]-tri-iodothyronine ([125I]T3).

2. Maternal blood, organs and foetuses were removed 1 and 4 h later, homogenized and trichloroacetic acid added to precipitate radio-labelled iodothyronines.

3. An hour after injecting [125I]thyroxine, 9–10 day old foetuses contained 21% of the radiolabel found in the same weight of plasma whereas by 13–14 days they contained 0.6%.

4. An hour after injection of [125I]tri-iodothyroninetri-iodothyronine, 9–10 day old foetuses contained 54% of the radioactivity present in the same weight of plasma.

5. When related to tissue protein, the radio-labelled iodothyronine content in 9–10 day old foetuses was comparable with that in maternal brain, heart or ovary.

6. De-iodination of [125I]thyroxine in 9–10 day old foetoplacental units was equal to that in maternal liver but greater than that in brain or heart.

7. It is concluded that substantial amounts of thyroxine and tri-iodothyronine enter the rat foetus in early pregnancy but thyroxine uptake may be minimal in later pregnancy.
Atrial Natriuretic Factor: Sodium Transport in Human Erythrocytes
Authors: Trippodo Nick C. , Cole Francis E. , MacPhee Allan A.
Published: August 2015

1. The effect of partially purified rat atrial natriuretic factor on sodium efflux from sodium-loaded human erythrocytes was studied.

2. High molecular weight (10000–30000) and low molecular weight (3000–10000) fractions of atrial extract were prepared by gel filtration; they had natriuretic activity in rats.

3. Neither fraction affected sodium efflux in erythrocytes.

4. The results suggest that atrial natriuretic factor acts in the kidney by mechanisms other than through inhibition of the Na+-K+ exchange pump or the Na+-K+ cotransport system.
Ouabain-Resistant, Frusemide-Sensitive Sodium Efflux in Human Lymphocytes: A Comparison of Normotensive and Hypertensive Subjects
Authors: Montanari A. , Simoni Isabella , Sani E. , Schianchi P. , Borghetti A. , Novarini A.
Published: August 2015

1. Peripheral blood lymphocytes were isolated at room temperature in a low sodium medium in 17 normotensive control subjects (NC) and 13 patients with essential hypertension (EHP).

2. Lymphocyte sodium content was not significantly different between NC and EHP (3.1 ± 0.5, n = 11, and 3.6 ± 0.5, n = 10, respectively; means ± sem).

3. The effect of frusemide on the ouabain-resistant rate constant of sodium efflux (KNao) from these lymphocytes into a sodium-free medium was measured.

4. The frusemide-sensitive efflux rate constant was 75 ± 5 μs (n = 17) in controls and significantly lower in EHP (32 ± 7 μs, n = 13, P<0.001).

5. In human lymphocytes there is a ouabain-resistant, frusemide-sensitive fraction of sodium efflux into a sodium-free medium; this fraction may be reasonably attributed to a sodium-potassium cotransport system. This sodium transport pathway seems to be reduced in lymphocytes from EHP.
Arterial Plasma Potassium Measured Continuously during Exercise in Man
Authors: Linton R. A. F. , Lim M. , Wolff C. B. , Wilmshurst P. , Band D. M.
Published: August 2015

1. Five continuous records of arterial plasma potassium were obtained from three normal subjects during brief periods (5–7 min) of exercise (100 W).

2. In two of these subjects hepatic venous blood samples were withdrawn at 0.5–1.0 min intervals and analysed in vitro for plasma potassium.

3. Arterial plasma potassium rose rapidly at the start of exercise from 3.8 ± 0.3 mmol/l (mean ± sd) to plateau levels of 5.4 ± 0.1 mmol/l.

4. One of the above subjects and a further subject were studied after β-blockade with propranolol. This resulted in an exaggerated rise in arterial plasma potassium during exercise.

5. Hepatic venous potassium measurements indicated that the liver probably had little effect on potassium changes during exercise.

6. The changes in arterial plasma potassium during exercise are rapid and substantial. If transmitted to the extracellular fluid these changes would alter cell transmembrane potential and might as a result alter receptor sensitivity.
The Effect of a 48h Fast on the Thermoregulatory Responses to Graded Cooling in Man
Authors: MacDonald I. A. , Bennett T. , Sainsbury R.
Published: August 2015

1. The thermoregulatory responses to graded cooling were measured in 11 healthy male subjects after a 12 h fast and after a 48 h fast. The cooling stimulus was produced by changing the temperature of the skin of the trunk and legs with a water-perfused suit. Five levels of skin temperature from 35.5 to 24°C were applied on each occasion.

2. After a 12 h fast, core temperature was maintained during cooling. This maintenance of core temperature was associated with an increase in metabolic rate and a reduction in blood flow to the hand and to the forearm.

3. After 48 h of fasting, the subjects could not maintain core temperature during cooling, and a decrease of 0.36 ± 0.05°C occurred as the suit temperature was reduced from 35.9 to 24°C. Metabolic rate was slightly higher after the 48 h fast than after the 12 h fast, but similar increases in metabolic rate were observed during cooling.

4. Vasoconstriction in the hand was initially less after a 48 h fast than after a 12 h fast, but at the lowest suit temperature, hand blood flow was similar, and low, on both occasions. After 48 h of fasting, forearm blood flow was elevated at all suit temperatures, being approximately twice the level recorded after the 12 h fast.

5. Venous plasma noradrenaline levels did not change during cooling after the 12 h fast, whilst after 48 h of fasting a significant increase in noradrenaline level was observed at the lowest suit temperature.

6. The results of this study provide further evidence that fasting induces an impairment of autonomic reflex mechanisms, but it is not clear whether this is due to a suppression of sympathetic nervous activity.
Effect of Hyperthyroidism on Hepatic Lipogenesis in Rats: Studies in Vivo and in Vitro
Authors: Al-Saadi Amal S. , Orr J. Stewart , Goode Anthony W. , Sugden Mary C.
Published: August 2015

1. Lipogenic rates (measured with 3H2O) in hepatocytes from fed or starved euthyroid rats were similar in magnitude to those measured in livers in vivo. Hepatic lipogenesis in vivo in fed triiodothyronine (T3)-treated rats was greater than in fed control rats, but rates in vitro were only 16% of those of control rats. It is concluded that hepatic lipogenesis in vivo in T3-treated rats utilizes precursors from extrahepatic tissues.

2. Glycogen depletion of hepatocytes from fed control rats decreased lipogenesis, and rates were then similar to those in hepatocytes from fed T3-treated rats. Addition of lactate (2 mmol/l) and pyruvate (0.2 mmol/l) had little stimulatory effect on lipogenesis in hepatocytes from fed control rats, but increased lipogenesis in glycogen-depleted hepatocytes (by 86%), hepatocytes from starved rats (by 25%) and hepatocytes from T3-treated rats (by 60%).

3. In the presence of lactate and pyruvate, 3-mercaptopicolinate (3-MPA) (an inhibitor of gluconeogenesis) did not affect lipogenesis in hepatocytes from fed control rats but substantially increased lipogenesis in hepatocytes from starved euthyroid rats or fed hyperthyroid rats. Thus, in hepatocytes from starved euthyroid rats or fed hyperthyroid rats gluconeogenesis competes with lipogenesis for available precursors (lactate and pyruvate). In contrast, in fed rats carbon flux is predominantly towards lipogenesis.

4. Effects of 3-MPA in the presence of lactate and pyruvate were much less in glycogen-depleted cells from fed rats than in hepatocytes from starved or T3-treated rats. Thus glycogen depletion per se does not cause a redirection of carbon flux.