bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of long-term circulatory occlusion on pH and energy metabolism of the quadriceps muscle in man
Authors: Sjöholm H. , Gidlöf A. , Larsson J. , Sahlin K. 
Published: August 2015

1. The effect of up to 2.5 h circulatory occlusion on muscle pH and energy metabolism of the quadriceps muscle was studied in 13 patients operated on for an inveterate knee injury. Muscle samples were taken by the percutaneous needle biopsy technique at different times during the arterial occlusion and after restoration of circulation.
2. Energy was provided by a complete utilization of phosphocreatine and by a low rate of glycolysis during 2 h of occlusion. The ATP level remained unchanged throughout the occlusion period.
3. Muscle pH decreased from 7.0-7.1 to about 6.8 after 2 h occlusion. Muscle pH was essentially normalized within 20 min after restoration of the blood flow.
Influence of age, sex and potassium excretion on urinary prostaglandins in children
Authors: Barden A. , Beilin L. J. , Vandongen R. , Rouse I. 
Published: August 2015

1. Measurement of urinary 6-ketoprostaglandin (PG) F1α and PGE2 excretion in 83 healthy children, aged 5-15 years, revealed that supervised 4 h urine collections under mild water diuresis provided more consistent results than overnight 12 h urine collections.
2. Males had higher urinary excretion of 6-keto-PGF1α but not of PGE2 compared with females.
3. Urinary potassium was related to 6-keto-PGF1α in both 4 and 12 h urine collections and urinary sodium to 6-keto-PGFα in 4 h collections only.
4. In the sexes combined multiple regression analyses revealed age as the only significant influence on prostanoid excretion (P = 0.001).
5. Thus age and sex and dietary potassium intake need to be considered in studies of urinary prostanoids in children.
Reduced plasma noradrenaline during angiotensin II-induced acute hypertension in man
Authors: Henriksen Jens H. , Kastrup Jens , Christensen Niels Juel 
Published: August 2015

1. Plasma noradrenaline and adrenaline concentrations were measured in ten subjects before, during and after intravenous infusion of angiotensin II (ANG II) in order to determine the sympathoadrenal response of ANG II challenge in man. In five subjects ganglionic blockade was additionally performed by intravenous infusion of trimethaphan.
2. During ANG II infusion mean arterial blood pressure increased by 30% (P&lt;0.001), and plasma noradrenaline decreased by 25% (P&lt;0.001). Plasma adrenaline decreased less.
3. During ganglionic blockade plasma noradrenaline decreased significantly (P&lt;0.005) and similarly to the decrease obtained with ANG II infusion.
4. The results indicate that a decrease in sympathoadrenal activity occurs during ANG II-induced acute hypertension in man. This may be elicited by the arterial baroreflex, which seems to dominate any direct sympathoadrenergic facilitating effect of ANG II.
Effect of angiotensin converting-enzyme inhibition on potassium-mediated aldosterone secretion in essential hypertension
Authors: Barnes J. N. , Drew P. J. T. , Furniss S. S. , Holly J. M. P. , Knight A. R. , Skehan J. D. , Goodwin F. J. 
Published: August 2015

1. Eight patients with essential hypertension were challenged with an infusion of 32 mmol of potassium chloride in saline before and after control of their blood pressure by the angiotensin converting-enzyme (ACE) inhibitor enalapril.
2. The potassium infusion was associated with similar increases in plasma aldosterone before and during enalapril treatment, although absolute aldosterone levels were lower after enalapril treatment despite higher plasma potassium levels.
3. The handling of the potassium load was altered by ACE inhibition. The area under the curve of a plot of the increase in plasma potassium above baseline against time was greater during enalapril treatment than during treatment with placebo.
4. These observations contrast with data obtained in the dog and demonstrate that in patients with essential hypertension stimulation of aldosterone secretion by potassium is not abolished by chronic suppression of plasma angiotensin II; and although plasma aldosterone remains at a lower level, the homoeostasis of plasma potassium is only mildly impaired.
Angiotensin II-induced thirst and vasopressin release in man
Authors: Phillips P. A. , Rolls B. J. , Ledingham J. G. G. , Morton J. J. , Forsling M. L. 
Published: August 2015

1. The thirst and plasma vasopressin responses to single-blind controlled intravenous angiotensin II infusions (2-16 ng min−1 kg−1) were investigated in ten healthy young men.
2. Thirst and vasopressin secretion were stimulated in four out of ten subjects. These effects occurred at plasma angiotensin concentrations well above those measured under physiological conditions associated with thirst and vasopressin secretion such as water deprivation.
3. Further studies are needed to define why only certain individuals respond to intravenous angiotensin II infusions and to determine whether potentiation of angiotensin-induced thirst and vasopressin secretion by other stimuli (e.g. hypovolaemia and hypertonicity) might occur in man, in particular under pathological conditions when plasma angiotensin levels are above the physiological range.
What do antagonists tell us about α-adrenoceptors?
Authors: Drew G. M. 
Published: August 2015

The early proposals that pre- and post-junctional α-adrenoceptors might be different stemmed largely from two separate observations. Firstly, the orders of potency of a series of agonists at inhibiting the response to sympathetic nerve stimulation and in increasing inotropic activity in the rabbit isolated heart were different [1, 2]. Secondly, phenoxybenzamine was more potent in inhibiting vasoconstrictor responses to sympathetic nerve stimulation than in increasing transmitter overflow from the cat spleen [3]. These experiments illustrate the most fundamental, pharmacological ways of distinguishing between receptors: namely, by comparing the relative potencies of agonists and/or antagonists in producing, or preventing, pharmacological effects.
There are, however, difficulties in using agonists to classify receptors because their ability to generate a response depends not only upon their intrinsic properties of affinity for, and efficacy at, the receptors but also upon the capacity of the tissue to translate the stimulus into a response. Thus agonists with a relatively low intrinsic efficacy may produce a small response, or no response at all, in a tissue in which the efficiency of the stimulus-response coupling mechanism is low. The importance of this phenomenon in influencing tissue responses to agonists with low efficacy has been demonstrated for the α-adrenoceptor agonist prenalterol [4] and for the α-adrenoceptor agonist oxymetazoline [5].
Attempts to uncover subtypes of α-adrenoceptors and associated mechanisms by using sequential administration of blocking drugs
Authors: Grant T. L. , Flavahan N. A. , Greig J. , McGrath J. C. , McKean C. E. , Reid J. L. 
Published: August 2015

1. By the sequential administration of α1- and α2-blockers it can be shown, in the pithed rabbit, that the dose/pressor response curve to noradrenaline consists of two separate curves, one for each receptor. α2-mediated responses predominate at low doses and α1-mediated responses predominate at high doses. Pressor responses to sympathetic nerve stimulation have, similarly, an α2 component at low frequencies and a dominant α1-mediated response at high frequencies: a residual response is resistant to combined α1- plus α2-blockade.
2. This α-blocker-resistant pressor nerve response was further analysed in the pithed rat and was found to be partly susceptible to α,β-methylene ATP, which densitizes purinergic responses. However, reserpine pretreatment produced a greater reduction of nerve-mediated pressor responses than did α-blockade, suggesting that part of the ‘α-blocker resistant’ response might be adrenergic.
3. It is concluded that sympathetic vasopressor nerve transmission is mediated for the greater part by α1- and α2-adrenoceptors but that there is evidence for contributions from non-α-adrenergic and ‘purinergic’ elements. An even greater proportion of the responses to circulating catecholamines is attributable to the α-receptors with a relatively small but significant ‘resistant’ component.
α-Adrenoceptor-effector coupling: affinity states or heterogeneity of the α2-adrenoceptor?
Authors: Nahorski S. R. , Barnett D. B. , Cheung Y.-D. 
Published: August 2015

Receptor-effector coupling
At the present time there is substantial evidence supporting the concept of at least two major groups of α-adrenoceptors, which have been termed α1 and α2 [1]. Whereas α1 and β2 adrenoceptors are linked positively to adenylate cyclase, it seems likely that α1- and α2-adrenoceptors possess different mechanisms for signal transduction.
Ca2+ sources mobilized by α1-receptor activation in vascular smooth muscle
Authors: Leijten P. , Cauvin C. , Lodge N. , Saida K. , Breemen C. Van 
Published: August 2015

1. We propose the following model of Ca2+ mobilization by noradrenaline in vascular smooth muscle. Upon receptor occupation Ca2+ from a labile small intracellular store on the inner plasmalemma is released. This Ca2+ does not function as activator Ca2+ but triggers Ca2+ release from the sarcoplasmic reticulum (Ca2+-induced Ca2+ release).
2. Simultaneously Ca2+ from an extracellularly bound store (on the external surface of the plasmalemma) is dislodged, which enters the cell through receptor linked channels.
3. These processes are responsible for the early ‘phasic’ component of the noradrenaline contraction. In addition, Ca2+ from the free extracellular Ca2+ pool enters through receptor operated channels, supporting the maintained tension development.
α-Adrenoceptor agonists and the Ca2+-dependence of smooth muscle contraction: evidence for subtypes of receptors or for agonist-dependent differences in the agonist-receptor interaction?
Authors: McGrath John C. 
Published: August 2015

1. The effects of varying [Ca2+]o on the contraction of smooth muscle by different α-adrenoceptor agonists were examined on rat isolated anococcygeus muscle. Agonists were tested in the presence of various [Ca2+]o or ‘Ca2+-re-addition curves’ were constructed. In some experiments the [Ca2+]free was buffered with EGTA and nitrilotriacetic acid. The components of the response which were revealed were further analysed by using drugs which modify Ca2+ mobilization.
2. Three separate elements in the contractile response were identified: (i) an initial transient contraction, due to intracellular Ca2+ release could be isolated with [Ca2+]o between 1 nmol/l and 3 μmol/l (this could be obtained only with noradrenaline, phenylephrine and amidephrine); (ii) a nifedipine-sensitive response requiring [Ca2+]o of 3 μmol/l or more; (iii) a nifedipine-resistant response requiring [Ca2+]o of 100 μmol/l or more. Presumably (ii) and (iii) involve the entry of Ca2+o: they could be obtained with all agonists tested, including these above, methoxamine, indanidine and xylazine.
3. The results are discussed in relation to the possibility of distinct types of response and their relationship to subgroups of receptors or agonists. It is concluded that there is a continuous spectrum of activity across the agonist range and that this is likely to correlate with ‘efficacy’ at a single α1 receptor type.
Evidence for ATP and noradrenaline as cotransmitters in sympathetic nerves
Authors: Burnstock G. , Sneddon P. 
Published: August 2015

Sympathetically innervated smooth muscles, including those in some arteries, arterioles, cat nictitating membrane and vas deferens, have α1-adrenoceptors which respond to exogenously applied noradrenaline (NA) by producing contractions which can be abolished by α1-adrenoceptor antagonists such as prazosin. Stimulation of the sympathetic nerves innervating these muscles causes release of NA and a contractile response. However, this contraction is (at least partly) resistant to specific α1-adrenoceptor antagonists. This apparent contradiction could be explained by a variety of ad hoc explanations (such as high transmitter concentrations within the nerve-muscle junction, or prejunctional enhancement of transmitter release by the antagonist due to prejunctional α2-adrenoceptor blockade etc.) but recently two hypotheses have been advanced which may have more fundamental implications for sympathetic neurotransmission. First, Hirst and Neild and their colleagues suggested that the electrical and mechanical responses of some smooth muscles were resistant to α-adrenoceptor antagonists because neuronally released NA was acting not only on α-adrenoceptors but also on a new class of adrenoceptors which they designated γ-receptors, located near the nerve-muscle junction. The crucial experiments in support of this hypothesis were originally performed on the arterioles of the guinea-pig submucosa [1], but the idea has been extended to include many other sympathetically innervated smooth muscles [2], including guinea-pig vas deferens, which was also the smooth muscle preparation in which the experimental evidence for an alternative hypothesis was obtained by Fedan et al. [3]. They proposed that the α-blocker-resistant portion of the contractile response to sympathetic nerve stimulation was mediated by ATP, acting as a cotransmitter with NA. Full details of the early development of the concept of cotransmission in sympathetic nerves have been reviewed previously [4, 6, 7].
The experimental evidence relating to the co-transmission hypothesis is outlined below, drawing mainly on results obtained in guinea-pig vas deferens, where most of the more recent experiments have been performed.
Functional consequences of contrasting properties of α1/α2 systems
Authors: Timmermans Pieter B. M. W. M. , Thoolen Martin J. M. C. , Jonge Adriaan De , Wilffert Bob , Zwieten Pieter A. Van 
Published: August 2015

Ample experimental evidence supports the existence of two distinct types of vasoconstrictor α-adrenoceptors in vascular smooth muscle at postjunctional sites, showing similarities with α1 and α2-adrenoceptors. Especially in vivo, the characterization of an α2-adrenoceptor mediating an increase in diastolic pressure has been most successful. In this respect the model of the pithed rat has been employed most frequently (for reviews see [1, 2]).
At present, the agents cirazoline, (−) phenylephrine, (±)-erythro-methoxamine, (−)-amidephrine, SKF89748, St587 and Sgd 101/75 fulfil the criteria for selective α1-adrenoceptor agonists; their log dose-vasopressor effect curves are virtually unaffected by previous treatment with yohimbine or rauwolscine (selective dose in pithed rats: 1 mg/kg), whereas prazosin (selective dose in pithed rats: 0.1 mg/kg) causes an appreciable parallel rightward displacement. The reverse holds true for the stimulants B-HT 920, B-HT 933, B-HT 958, UK-14304, xylazine, TL-99, M-7 and DP-6,7-ADTN, which all have been classified as preferential agonists of vascular postjunctional α-adrenoceptors.
Evidence for the involvement of α1-adrenoceptors in negative feedback regulation of noradrenergic transmitter release in rat atria
Authors: Story D. F. , Standford-Starr C. A. , Rand M. J. 
Published: August 2015

1. Experiments were undertaken to determine if prejunctional α1-adrenoceptors are involved in autoinhibitory regulation of transmitter noradrenaline release in rat atria.
2. The noradrenergic transmitter stores in rat isolated atria were radiolabeled with [3H]noradrenaline and transmitter release was deduced from the efflux of the radiolabel evoked by field stimulation of the atrial intramural sympathetic nerves.
3. Phentolamine (3 μmol/l) and prazosin (0.1 and 3 μmol/l) enhanced the release of radiolabel evoked by stimulation with trains of 4, 8 and 16 pulses, whereas idazoxan (10 μmol/l) enhanced release evoked by stimulation with 8 and 16 pulses. Idazoxan and prazosin were about equieffective in enhancing the evoked release but phentolamine produced much greater enhancement than either idazoxan or prazosin.
4. Combination of idazoxan (10 μmol/l) and prazosin enhanced the stimulation-evoked release with 4, 8 and 16 pulses to the same extent as phentolamine (3 μmol/l).
5. The selective α1-adrenoceptor agonist methoxamine (10 μmol/l) inhibited stimulation-evoked release and this effect was blocked by the α1-adrenoceptor antagonist prazosin (0.1 μmol/l).
6. The findings indicate that α1-adrenoceptors may contribute to autoinhibitory feedback regulation of transmitter release in rat atria.
Metabolic and haemodynamic effects of α2-adrenoceptor stimulation and antagonism in man
Authors: Brown M. J. , Struthers A. D. , Silvio L. Di , Yeo T. , Ghatei M. , Burrin J. M. 
Published: August 2015

1. Six healthy volunteers received a 60 min infusion of guanfacine (α2-agonist) on two occasions, preceded by either idazoxan (α2-antagonist) or vehicle.
2. Idazoxan elevated blood pressure by 8/7 mmHg, but there was no change on either day during guanfacine infusion.
3. Guanfacine reduced plasma noradrenaline by approximately 30%, and this was not antagonized by idazoxan. By contrast, the 30-fold increase in plasma growth hormone caused by guanfacine was almost completely blocked by idazoxan.
4. Guanfacine caused a two- to three-fold increase in plasma glucagon and a similar reduction in plasma insulin. Only the latter was antagonized by idazoxan. No consistent changes in plasma ACTH were observed after either idazoxan or guanfacine.
5. Idazoxan itself elevated plasma noradrenaline up to twice baseline values, but did not affect the other metabolic measurements.
6. α2-Adrenoceptor stimulation plays a minor role in control of hormone release but has a greater physiological role in regulating release of the neurotransmitter, noradrenaline.
Extracellular Elastolytic Activity in Human Lung Lavage: A Comparative study between Smokers and Non-Smokers
Authors: Smith S. F. , Guz A. , Cooke N. T. , Burton G. H. , Tetley T. D. 
Published: August 2015

1. Unrestrained proteolysis in the lung is believed to initiate emphysema, a disease common among tobacco smokers. However, few studies have found extracellular protease activity in human lung lavage.
2. In this investigation, elastase and serine protease activities were measured in broncho-alveolar lavage supernatants (BAL) from patients undergoing routine investigations. Significantly more elastolytic activity (against insoluble [3H]-elastin) was recovered in the lavage of smokers than that of non-smokers. However, no significant difference was found when the levels of serine proteolytic activity (against N-succinyl-L-trialanyl-p-nitroanilide) were compared.
3. The elastolytic component of the protease activity rose from 5% in non-smokers’ BAL to over 30% in that of smokers, suggesting that elastase activity is selectively enhanced by smoking. In lavages from most smokers, 80% or more of the elastase activity was serine-dependent, whereas lavages from non-smokers contained variable proportions of serine elastase.
4. Both α1-proteinase inhibitor (α1-PI) and a low molecular weight antiprotease, bronchial mucus proteinase inhibitor (BMPI) were detectable in the lavage samples, the latter contributing up to 76% of the total antiprotease quantified in the lavage. Functional antiprotease was detected in 85% of the lavages.
5. Since there were no differences in either antiprotease levels or functional inhibitory capacities between lavages from smokers and controls, it is concluded that the imbalance in the protease/antiprotease profile of the smokers’ lung results from an enhancement of proteases, specifically of elastolytic activity, rather than a reduction in inhibitory capacity.
The effect of Pyridoxine on Oxalate Dynamics in three Cases of Primary Hyperoxaluria (with Glycollic Aciduria)
Authors: Watts R. W. E. , Veall N. , Purkiss P. , Mansell M. A. , Haywood E. F. 
Published: August 2015

1. We have measured glomerular filtration rate (GFR), extracellular fluid volume (ECF), oxalate distribution volume (OxDV), plasma oxalate concentration (POx.), plasma total clearance of oxalate (PCOx.), oxalate metabolic pool size [(OxDV) × (POx.)], renal clearance of oxalate (RCOx.), oxalate excretion, tissue clearance of oxalate (TCOx.) and tissue oxalate accumulation rate [(TOx.A) = (TCOx.) × (POx.)] in three patients with type I primary hyperoxaluria (hyperoxaluria with hypergrycollic aciduria) when they were taking pyridoxine and after discontinuation of the vitamin.
2. Seven days after stopping pyridoxine the plasma oxalate concentration, oxalate metabolic pool size and the urinary excretion of oxalate had all increased between seven- and eight-fold in two of the patients. The third patient showed no changes on stopping pyridoxine.
3. These results support the view that pyridoxine acts by reducing oxalate biosynthesis in some patients with type I primary hyperoxaluria.
4. The possible biochemical basis for this effect is discussed.
Leg Metabolism of Amino Acids and Ammonia in Patients with Chronic Renal Failure
Authors: Deferrari Giacomo , Garibotto Giacomo , Robaudo Cristina , Canepa Alberto , Bagnasco Serena , Tizianello Alberto 
Published: August 2015

1. Leg metabolism of amino acids and ammonia in the postabsorptive state was evaluated in 10 patients with chronic renal failure (CRF) and in 10 patients with normal renal function (controls) by measuring the arterial-femoral venous (A-FV) differences for free amino acids and ammonia.
2. Total amino acid release from the leg and alanine and glutamine release, which accounts for the greatest amount of the total amino acid release, are similar in patients and controls. Total amino acid uptake from the arterial blood and glutamate uptake, which is the amino acid extracted at the highest rate, are comparable in both groups. Taken together these data, in addition to the similarity of A-FV differences for proteolytic markers, namely tyrosine, phenylalanine and histidine, suggest that protein breakdown in peripheral tissues is not increased in patients with CRF.
3. In CRF selective metabolic abnormalities for some amino acids are evident. Whilst only the A-FV differences for valine, leucine and isoleucine are decreased, additional alterations are observed by relating the A-FV difference for each amino acid to that of proteolytic markers. Such a procedure demonstrates that in CRF histidine release relative to that of proteolytic markers is reduced, whereas proline and arginine release is increased.
4. In CRF the reduced release of some amino acids, mainly branched-chain amino acids, by the leg probably affects the pattern of circulating amino acids.
5. Finally, both in patients and in controls a significant uptake of ammonia is observed; the ammonia uptake is related to arterial levels of this metabolite, confirming the role of peripheral tissues in removing ammonia from circulation.