bluuebunny/crossref_metadata_2025 huggingface dataset:
QUANTITATIVE CHANGES IN THE RAT PULMONARY VASCULATURE IN CHRONIC HYPOXIA ‐ RELATION TO HAEMODYNAMIC CHANGES
Authors: Finlay Michael , Barer Gwenda R. , Suggett Andrew J.
Published: December 2014

The anatomical basis of resistance and compliance changes of the pulmonary arterial bed was studied in rats exposed to chronic hypoxia (10% O2, 3 weeks) and the findings were compared with those of normoxic rats. The lungs were perfused with a Ba‐gelatine mixture at different pressures and studied by radiology and histology. The diameter of the pulmonary arteries (〉 0·5 mm), measured from X‐rays, was less in chronically hypoxic than normoxic rats when filled at the same perfusion pressure. Diameters increased in both groups with increasing perfusion pressure but at a given pressure those of chronically hypoxic rats were always smaller than those of normoxic rats. We found evidence that arterial length was increased in chronically hypoxic rats. Arterioles of 50 µm or less in diameter adjacent to gas exchange units were of similar external diameter in normoxic and chronically hypoxic rats, but most of the latter had developed a muscular coat and a second elastic lamina internal to the single elastic lamina of control arterioles. These changes reduced the lumen by an estimated 10‐14% and would increase pulmonary arteriolar resistance in chronically hypoxic rats, resulting in a changed pressure profile. We found no evidence of arteriolar loss in chronically hypoxic rats although at a given pressure, the Ba‐gelatine mixture penetrated less far for reasons which are discussed.
AN INVESTIGATION OF [3H]BUMETANIDE UPTAKE IN A CULTURED RENAL CELL LINE (MDCK)
Authors: Rugg E. L. , Tivey D. R. , Simmons N. L.
Published: December 2014

The inhibition of ouabain‐insensitive 86Rb+(K+) flux in a cultured renal cell line (MDCK) by a series of loop diuretics, including bumetanide, (the ‘cotransport’ flux component) has been determined in order to define the concentration range over which [3H]bumetanide would be expected to bind to the membrane transporter involved. Half‐maximal inhibition by bumetanide was observed at 0·26±0·12 (S.D.) µM. The time and concentration dependence of [3H]bumetanide uptake in intact MDCK cells has been determined in experimental conditions, which were as far as possible, identical to inhibition of K+ flux. Total cellular uptake of [3H]bumetanide (0‐1 µM) may be separated into a linear component and a component displaying sigmoidal saturation kinetics with a concentration giving half‐maximal uptake of 0·33±0·17 (S.D.) µM, maximal uptake of 1·17±0·47 pmol/106 cells, and a Hill coefficient of 1·59±0·28. There is also evidence for a second component of [3H]bumetanide uptake of lower affinity (〈 5 µM). Competition of [3H]bumetanide uptake by a series of loop diuretics at varying concentrations gives an order of potency identical to that observed for inhibition of the ouabain‐insensitive 86Rb+ influx. The magnitude of the saturable component of [3H]bumetanide uptake is correlated with the magnitude of the diuretic‐sensitive 86Rb+ influx in MDCK cells and in a variety of other cultured cells. The relationship between the diuretic‐sensitive transport, the saturable component of [3H]bumetanide uptake and the cellular location of bumetanide uptake is discussed.
LOOP‐DIURETIC INHIBITION OF ADRENALINE‐STIMULATED Cl‐ SECRETION IN A CULTURED EPITHELIUM OF RENAL ORIGIN (MDCK)
Authors: Brown C. D. A. , Rugg E. L. , Simmons N. L.
Published: December 2014

Loop diuretics (furosemide, bumetanide, piretanide) inhibit the adrenaline‐stimulated short‐circuit current due to transepithelial Cl— secretion in cultured renal epithelial layers (MDCK). The inhibition of Cl— secretion by loop diuretics is consistent with the presence of basal‐lateral ‘cotransport’ since inhibition is observed only with the basal applications of loop diuretics, is of high potency (half‐maximal bumetanide inhibition being observed at 0·8 µM, bumetanide being more potent than furosemide) and is without effect upon the adrenaline‐stimulated increase in tissue conductance. Loop diuretics are also shown to inhibit a component of K+ efflux across the basal‐lateral surfaces. Cellular uptake of [3H]bumetanide across both apical and basal surfaces of intact epithelial layers was measured in order to localize the cotransport system. A component of cellular [3H]bumetanide uptake sensitive to competition by 0·1 mM unlabelled loop diuretic is only observed from the basal‐lateral cell surfaces. There is no evidence for transepithelial bumetanide secretion as is seen in renal cortex.
TISSUE METABOLISM STUDIED IN VIVO BY NUCLEAR MAGNETIC RESONANCE
Authors: Williams Stephen R. , Gadian David G.
Published: December 2014

N.m.r. is finding increasing application as a non‐invasive method of studying metabolism in vivo. 31P n.m.r. is particularly useful for studies of energy metabolism, while other nuclei, in particular 1H, 13C and 19F, can provide additional information about certain aspects of cellular metabolism that are not amenable to investigation by 31P n.m.r. The major problem with n.m.r. is lack of sensitivity. The main implications of this are first that signals can only be detected from metabolites that are present at fairly high concentrations, and secondly that the spatial resolution for localized studies, particularly of internal regions of the body, is limited. N.m.r. could considerably enhance our understanding of metabolic abnormalities in disease, but the precise role of such metabolic studies in a clinical setting remains to be evaluated.
ULTRASTRUCTURAL EVIDENCE IN RABBIT EAR ARTERIES THAT BARIUM ENTERS SMOOTH MUSCLE CELLS THROUGH CALCIUM CHANNELS
Authors: Gilmore Ruth St C. , Bullock Caroline G. , Sanderson Gwendolyn , Wallace William F. M.
Published: December 2014

The calcium channel blocker methoxyverapamil, at 10−5 mol/l, abolished contractile responses of isolated perfused rabbit ear arteries to barium. Entry of barium into smooth muscle cells was detected by the presence of mitochondrial granules specific for barium. Methoxyverapamil (10−5 mol/l) prevented the appearance of barium granules. In a further series of experiments, eight out of twelve arteries incubated with barium, 2·5 mmol/l, showed granules; when the incubate contained 2·5 mmol/l of both barium and calcium, granules were found in only one of twelve specimens; thus calcium appears to compete with barium for entry. These results are consistent with the hypothesis that contractile responses to barium depend on entry of barium into the cells through calcium channels.
FREE INTRACELLULAR MAGNESIUM CONCENTRATION IN FERRET VENTRICULAR MUSCLE MEASURED WITH ION SELECTIVE MICRO‐ELECTRODES
Authors: Blatter L. A. , McGuigan John A. S.
Published: December 2014

The free Mg concentration ([Mg]i) was measured in ferret ventricular muscle using single‐barrelled Mg‐sensitive micro‐electrodes. The electrodes were calibrated in solutions containing the [K]i and [Na]i measured in this tissue. In thirteen measurements from seven experiments conforming to strict criteria for calibration and penetration the estimated mean [Mg]i was 0·4 mmol/l. This is to be regarded as an upper limit since it was estimated by linear extrapolation of the calibration curve.
HIND‐LIMB VASCULAR RESPONSES IN ANAESTHETIZED DOGS TO AORTIC ROOT INJECTIONS OF VERATRIDINE
Authors: McGregor K. H. , Hainsworth R. , Ford R.
Published: December 2014

In dogs anaesthetized with chloralose we determined the reflex responses of the blood vessels in the vascularly isolated hind limb to injection of veratridine into the aortic root. The presence of a cannula tied in the ascending aorta ensured that responses were due to stimulation of nerves only in the region perfused by the coronary arteries. Injections of veratridine resulted in transient decreases in vascular resistance and in venous resistance in a perfused cutaneous vein. The responses were reduced when carotid perfusion pressure was elevated. The afferent pathway for the reflex lay in the vagus nerves and the efferent pathway to the limb was in the sciatic and femoral nerves, but the vasodilatation was shown to be predominantly non‐cholinergic.
THE DEPENDENCE OF THE STRENGTH OF SODIUM‐DEPLETION CONTRACTURES OF ISOLATED FROG ATRIAL TRABECULAE ON THE MEMBRANE POTENTIAL
Authors: Chapman R. A. , Rodrigo Glenn C.
Published: December 2014

When the Na bathing isolated frog atrial trabeculae voltage clamped at ‐80 mV is reduced, a strong contracture develops. Upon return to normal extracellular Na concentration ([Na]o) this contracture rapidly relaxes. Hyperpolarization of the membrane by a voltage‐clamp pulse during the low‐Na contracture produces a rapid relaxation and the extent of this relaxation is dependent upon the size of the hyperpolarizing pulse. The membrane potential at which tension is relaxed to a constant level during low‐Na perfusion, is exponentially related to the change in the Na gradient. This relationship shows that changes in the Na gradient, across the cell membrane, have nearly three times more effect on the generation of tension than changes in membrane potential. This would be consistent with the notion that contracture tension is determined by an electrogenic Na/Ca exchange across the cell membrane with a coupling ratio approaching 3 Na+/Ca2+. Exposure of the muscle to strophanthidin reduces the size of the hyperpolarizing pulse required to relax completely the low‐Na contracture. As a consequence the apparent coupling ratio is increased to just above 3 Na+/Ca2. Upon repolarization to ‐80 mV in low‐Na Ringer solution, the redeveloped tension may be larger than that recorded immediately before the hyperpolarizing pulse. This after‐effect suggests that hyperpolarization of the membrane may reduce the fall in intracellular [Na] that normally occurs when the bathing [Na] is reduced.
EFFECT OF DRUGS, HORMONES AND ELECTRICAL FIELD STIMULATION ON ISOLATED MUSCLE STRIPS FROM HUMAN CHOLEDOCHODUODENAL JUNCTION
Authors: McKirdy H. C. , Marshall R. W. , Griffin P.
Published: December 2014

The behaviour of in vitro strips from the human choledochoduodenal junction would appear to be related to the anatomical location of origin of the strip. Strips from the papillary region showed low tone and obvious spontaneous rhythmic contractions (0·5‐6/min). Strips from the region of the inferior choledochal sphincter showed, in ten out of fifteen specimens, spontaneous myogenic tone and gave a relaxation or a biphasic response (relaxation followed by contraction) to electrical field stimulation (0·3 ms pulses at 10 Hz for 5 s). All strips from human choledochoduodenal junction are remarkably insensitive to a variety of gastrointestinal hormones and to opioid agents.
THE POSSIBLE ROLE OF PERIODONTAL MECHANORECEPTORS IN THE CONTROL OF PAROTID SECRETION IN MAN
Authors: Hector M. P. , Linden R. W. A.
Published: December 2014

In man, parotid flow has been recorded bilaterally using modified Lashley cups in response to mechanical stimulation of the teeth. The stimulus was defined and controlled by monitoring the rectified and integrated masseter electromyographic activity (e.m.g.) during repeated clenching on closely fitting bite‐blocks placed between the molar teeth. Unilateral clenching on a bite‐block resulted in a greater flow from the ipsilateral than the contralateral gland, and both exceeded the control values. There was also a positive correlation between the masseter e.m.g. activity and ipsilateral parotid flow. Parotid flow was also recorded before and during local anaesthesia of various intra‐oral branches of the trigeminal nerve. Anaesthesia of two to three inputs always produced significant reductions in ipsilateral flow, but anaesthesia of a single input was not always effective. These results provide evidence in support of the hypothesis that intra‐oral mechanoreceptors, particularly periodontal mechanoreceptors, are involved in the masticatory‐salivary reflex.
THE EFFECTS OF FEEDING EITHER HAY OR GRASS DIETS ON SALIVARY PHOSPHORUS SECRETION, NET INTESTINAL PHOSPHORUS ABSORPTION AND ON THE PARTITION OF PHOSPHORUS EXCRETION BETWEEN URINE AND FAECES IN THE SHEEP
Authors: Scott D. , Buchan W.
Published: December 2014

Mature sheep fitted with ruminal and duodenal cannulas were fed either a pelleted hay or a pelleted grass diet with or without supplementary phosphorus. Salivary phosphorus secretion, net intestinal phosphorus absorption and the route of phosphorus excretion were determined. The route of excretion was markedly affected by diet with urinary excretion being much higher and faecal excretion lower when the grass diet was fed. These effects were not due to differences in phosphorus intake or to differences in net intestinal phosphorus absorption. Salivary phosphorus secretion was, however, lower when the grass diet was fed. The significance of these changes in relation to the control of phosphorus balance in ruminants is discussed.
THE VAGAL AND SPINAL INNERVATION OF THE GASTRO‐DUODENAL JUNCTION OF SHEEP
Authors: Cottrell D. F. , Greenhorn J. G.
Published: December 2014

This paper describes the distribution of vagal afferent, vagal preganglionic and thoraco‐lumbar spinal afferent neurones to the gastro‐duodenal junction of sheep which may form part of the structural basis for duodeno‐gastric reflex mechanisms. After retrograde transport of cholera toxin‐horseradish peroxidase (CT‐HRP) from subserosal micro‐injections into the gastro‐duodenal junction, light‐microscopic examination revealed CT‐HRP‐labelled cell bodies projecting from the medulla oblongata and the dorsal root ganglia. Medullary cell bodies were distributed bilaterally in the dorsal motor nucleus of the vagus (d.v.m.n.) 4·50 mm rostral and 2·52 mm caudal to a transverse plane through the obex. The sizes of brain‐stem cell bodies, the extent of their dendritic arborization, axonal structure and orientation are described. Spinal sensory neurones were distributed to the thoraco‐lumbar dorsal root ganglia T6‐L3. Labelled cells and axons were found in the left and right vagal nodose ganglion. No labelled material was present in the lateral columns of the thoraco‐lumbar spinal cord. A brain‐stem map of medullary neurones was constructed from coronal sections of cresyl fast violet material. This enabled comparison between preparations and confirmed that all CT‐HRP‐labelled cell bodies and dendritic projections in the brain stem were confined to the d.v.m.n.
ROLE OF ACTIVITY‐INDUCED THERMOGENESIS IN TWENTY‐FOUR HOUR ENERGY EXPENDITURE OF LEAN AND GENETICALLY OBESE (OB/OB) MICE
Authors: Dauncey M. J. , Brown D.
Published: December 2014

The contribution made by spontaneous physical activity to 24 h energy expenditure has been assessed in lean and ob/ob mice living at 28°C. Measurements were made in young animals when the ob/ob mice were the same body weight as their lean littermates, and again when they were adult and the ob/ob mice were twice as heavy as their littermates.

In the young ob/ob mice, not only was 24 h heat production lower than in their lean littermates (P 〈 0·005) but so also was motor activity (P 〈 0·01). In adults, total 24 h heat production was similar in lean and obese animals, and thus on the basis of metabolic body size it was considerably lower in the obese adults (P 〈 0·005). The obese adults were also significantly less active than their lean littermates (P 〈 0·05). Differences between genotypes were particularly marked during the night. Partition of 24 h energy expenditure into the two components of rest and activity showed that in the young ob/ob mice the lower heat production occurred because they expended 31% less energy on rest and 47% less on activity than did their lean littermates. In the obese adults, the lower heat production per unit metabolic body size was accounted for by 16% less energy being expended on rest and 74% less on activity than in the lean mice. It is concluded that differences in motor activity between lean and ob/ob mice could account, at least in part, for the development and maintenance of obesity in these animals.
THE NEGATIVE INOTROPIC EFFECT OF RAISED EXTRACELLULAR POTASSIUM AND CAESIUM IONS ON ISOLATED FROG ATRIAL TRABECULAE
Authors: Chapman R. A. , Rodrigo Glenn C.
Published: December 2014

The exposure of frog atrial trabeculae to Ringer solution containing an elevated K+ concentration, produces a depolarization of the membrane and a reduction of both the duration of the action potential and the strength of the heart beat. In voltage‐clamped preparations, the effect of perfusion with K+‐rich Ringer solution is threefold. First, a sustained inward current develops at the holding potential (‐80 mV). Secondly, the contractions evoked by depolarizing clamp pulses are reduced: this effect which is greater upon the tonic phase of the contraction than the early phasic tension, is also seen to follow the addition of Cs+ ions to the bathing fluid; at equal concentrations K+ ions are the more effective. Thirdly, when measured with an ion‐sensitive micro‐electrode in ventricular trabeculae, the intracellular Na+ ion activity (aiNa) declines with a time course similar to the development of the negative inotropic effect. This suggests that the actions of raised [K+]o or [Cs+]o upon tension may be secondary to an effect on the movement of Na+ ions across the cell membrane, which by reducing aiNa may affect tension by way of the Na‐Ca exchange.
FRUCTOSE DISPOSAL AND OXIDATION RATES IN THE OVINE FETUS
Authors: Meznarich Huei Kang , Hay William W. , Sparks John W. , Meschia Giacomo , Battaglia Frederick C.
Published: December 2014

Fructose disposal and oxidation rates were measured in fetal lambs receiving a constant intravenous infusion of D‐[U‐14C]fructose. Approximately 60% of the infused tracer entered the placenta, but loss of fructose into the maternal circulation was negligible. Fructose was metabolized to lactate and CO2 in both the placenta and fetus, whereas there was no detectable conversion to glucose. In well‐fed ewes the fetal disposal and utilization rates of fructose were 2·41±0·17 and 0·97±0·09 mg/min.kg, respectively. The umbilical excretion rate of CO2 originating from the oxidation of fetal fructose was 18·1±1·3 µmol/min.kg or 5·3% of total fetal CO2 production. This excretion rate is one‐fifth of the CO2 excretion rate from fetal glucose carbon. In four ewes comparison of fructose metabolism in the fed and fasted states showed a significant decrease of fructose production and oxidation with fasting. Although fructose is present in high concentrations in the fetal blood of ungulates, its contribution to fetal oxidative metabolism is relatively small in comparison to glucose.
THE RELATIONSHIP BETWEEN UREA AND PYRIMIDINE DE NOVO SYNTHESIS IN RUMINANT LIVER
Authors: Motyl Tomasz , Orzechowski Arkadiusz , Pierzynowski Stefan
Published: December 2014

The influence of ammonia and inhibition of the urea cycle by norvaline on orotic acid synthesis in five Polish Merino ewes was investigated. The sheep were exposed to 60 min of successive infusions of 0·9% NaCl, NH4Cl (20 µmol kg‐1 min‐1), and NH4Cl with DL‐norvaline (10 µmol kg‐1 min‐1) solutions administered to the mesenteric vein. The average rate of orotic acid output, urea output and ammonia uptake in the liver in control conditions (infusion of 0·9% NaCl) was: 1·09 nmol g‐1 min‐1 0·97 µmol g‐1 min‐1 and 0·94 µmol g‐1 min‐1, respectively. Ammonia significantly stimulated the orotic acid output, urea output and ammonia uptake. At the same time liver uptake of glutamic acid, alanine and glycine increased. Norvaline as a competitive inhibitor of ornithine transcarbamylase depressed citrulline release and urea output in the liver, and elevated, although not significantly, the orotic acid output. It was concluded that ammonia stimulates the de novo synthesis of pyrimidine in the sheep liver but the participation in this effect of carbamyl phosphate generated in the urea cycle is limited.
THE ULTRASTRUCTURE OF FROG MICROVESSELS FOLLOWING PERFUSION WITH THE IONOPHORE A23187
Authors: Clough Geraldine , Michel C. C.
Published: December 2014

The ultrastructure of frog mesenteric capillaries and venules has been examined after the permeability of these vessels to fluid and macromolecules has been increased to a measured extent by perfusion with the ionophore A23187. An average 4·5‐fold increase in hydraulic permeability in thirteen vessels was associated with the presence of gaps between the endothelial cells and marked attenuation of endothelial cytoplasm with the appearance of many fenestrations. The changes in ultrastructure suggested much larger increments in permeability than had been measured in these same vessels in vivo.
IS VIP THE PUTATIVE NON‐CHOLINERGIC, NON‐ADRENERGIC NEUROTRANSMITTER CONTROLLING PROTEIN SECRETION IN RAT LACRIMAL GLANDS?
Authors: Hussain Munir , Singh Jaipaul
Published: December 2014

In the combined presence of cholinergic and adrenergic antagonists, electrical field stimulation (FS) caused a marked reversible increase in protein output from superfused rat lacrimal gland segments. The FS‐evoked protein output was abolished by the nerve blocking drug tetrodotoxin (TTX; 10−6 M) whereas high potassium (K+; 100 mM) continued to elicit secretion. Vasoactive intestinal polypeptide (VIP), but not adenosine 5'‐triphosphate (ATP), stimulated protein secretion in a manner almost identical to that observed in response to FS. The results suggest that the non‐cholinergic, non‐adrenergic secretory response may involve VIP as an endogenous neurotransmitter.
THE ROLE OF THE ABDOMINAL VISCERAL INNERVATION AND 5‐HYDROXYTRYPTAMINE M‐RECEPTORS IN VOMITING INDUCED BY THE CYTOTOXIC DRUGS CYCLOPHOSPHAMIDE AND CIS‐PLATIN IN THE FERRET
Authors: Hawthorn J. , Ostler K. J. , Andrews P. L. R.
Published: December 2014

We have used the ferret as an animal model to investigate the emetic action of the cytotoxic drugs cyclophosphamide and cis‐platin. Using selective nerve lesions, a crucial role for the abdominal innervation in the genesis of retching and vomiting in response to these agents has been demonstrated. A combination of bilateral abdominal vagotomy and greater splanchnic nerve section can totally abolish retching and vomiting in response to intraperitoneal cis‐platin or intravenous cyclophosphamide. Intraperitoneal cyclophosphamide still produced retching but vomiting was markedly reduced, demonstrating complex and probably separate control mechanisms for retching and vomiting. The effect of a widely used anti‐emetic, metoclopramide, was compared to that of nerve lesions. While effective this compound did not totally control retching or vomiting to either drug. Recent studies have attributed metoclopramide's action to its ability to antagonize 5‐HT M‐receptors (5‐HT‐3 receptors). Therefore we investigated BRL 24924, a gastro‐kinetic agent with more specific 5‐HT M‐receptor antagonist properties. This agent was extremely potent in almost totally abolishing retching and vomiting in response to cyclophosphamide, given by either an intravenous or intraperitoneal route, and totally abolished cis‐platin‐induced vomiting for at least 4 h. Clearly the abdominal visceral innervation plays a complex and major role in the emesis produced by these two cytotoxic drugs; circumstantial evidence suggests that 5‐HT M‐receptors on visceral afferent nerves mediate this action, but other possibly central sites of action of the 5‐HT M‐receptor antagonists cannot be excluded.
INFLUENCE OF SODIUM SALTS OF SATURATED MEDIUM CHAIN LENGTH (C6, C9, C10 AND C12) DICARBOXYLIC ACIDS ON THE UTERINE HORN OF RAT IN VITRO
Authors: Mingrone G. , Mancinelli R. , Metro D.
Published: December 2014

The influence of the sodium salt of some dicarboxylic acids (adipic acid, C6; azelaic acid, C9; sebacic acid, C10; dodecandioic acid, C12) on both spontaneous and evoked activity of uterine horn of rats has been studied in vitro. Spontaneous activity of uterine muscle was inhibited by dicarboxylic salts (DS) causing the total abolition of mechanical events at concentrations of 64 x 10−3 M‐C6, 40 x 10−3 M‐C9, 32 x 10−3 M‐C10 and 24 x 10−3 M‐C12. Dicarboxylic salts antagonized the maximal isometric contraction of the uterine horn induced by administration of acetylcholine, oxytocin or prostaglandins (PGF2a). The amount of antagonism was dependent upon the concentration of DS used. Dicarboxylic salt showed an aspecific inhibitory effect on the uterine horn which progressively increased with their chain length (C12 〉 Cl0 〉 C9 〉 C6). The results suggested that the inhibitory effects of DS on smooth muscle could be due to a cellular membrane hyperpolarization.
[3H]BUMETANIDE BINDING AND INHIBITION OF Na+ + K+ + Cl− CO‐TRANSPORT: DEMONSTRATION OF SPECIFICITY BY THE USE OF MDCK CELLS DEFICIENT IN CO‐TRANSPORT ACTIVITY
Authors: Popowicz P. , Simmons N. L.
Published: December 2014

Cultured renal MDCK cells possess a Na+ + K+ + Cl- co‐transport system which is inhibited with high affinity by loop diuretics (K0·5 for bumetanide inhibition = 0·28 µM). By the use of ‘mutant’ cell lines deficient in co‐transport flux the specific interaction of [3H]bumetanide with the co‐transporter has been identified. [3H]Bumetanide uptake in parental MDCK‐N cells in the range 0‐1 µM comprises a non‐saturable linear component, assessed by the inclusion of 100 µM‐unlabelled bumetanide and a saturable component (K0·5 = 0·19 µM and Bmax = 0·55 pmol/106 cells). Though the magnitude of the linear non‐specific component was little diffe; ent between the parental MDCK‐N cell line and two co‐transport‐deficient mutant cell lines (LKC1 and LKA3), the magnitude of the saturable component was markedly reduced in both co‐transport‐deficient mutants. In addition to the saturable component associated with flux inhibition a lower‐affinity uptake displaceable by excess unlabelled bumetanide was evident in MDCK‐N cells comprising 8 pmol/106 cells measured at 10 µM‐[3H]bumetanide. This lower‐ affinity uptake was present in both co‐transport‐deficient mutant cell lines confirming its lack of association with inhibition of co‐transport flux. In MDCK cells possessing the co‐ transporter, an estimate of the turnover number was made when co‐transport flux and specific bumetanide uptake at 0·5 µM‐[3H]bumetanide were measured in the same cell batch. At 37 °C this was 113 K+ ions site−1 s−1.
THE EFFECTS OF FEEDING PELLETED DIETS MADE FROM EITHER COARSELY OR FINELY GROUND HAY ON PHOSPHORUS BALANCE AND ON THE PARTITION OF PHOSPHORUS EXCRETION BETWEEN URINE AND FAECES IN THE SHEEP
Authors: Scott D. , Buchan W.
Published: December 2014

Mature sheep fitted with rumen and duodenal cannulae were fed pelleted diets made from hay that had been either coarsely or finely ground. The diets were supplemented with phosphorus and the effects on salivary phosphorus secretion, net intestinal phosphorus absorption and the route of excretion were examined. Changing the particle size of the diet had no effect on overall phosphorus balance but did affect the route of excretion with urine levels being higher and faecal levels lower in periods when the more finely ground diet was fed. This increase in urine excretion was not due to differences in phosphorus intake nor could it be attributed to increased net phosphorus absorption from the intestine. Salivary phosphorus secretion was, however, lower when the more finely ground diet was fed and it would appear that this change in the balance between that absorbed relative to its secretion back into the gut was the major factor contributing to the increased phosphorus excretion in the urine. The significance of these findings in relation to the high levels of phosphorus normally found in the urine of sheep fed concentrate diets compared to those fed roughage diets is discussed.
REFLEX VASCULAR RESPONSES TO CHANGES IN LEFT VENTRICULAR PRESSURE IN ANAESTHETIZED DOGS
Authors: Tutt S. M. , McGregor K. H. , Hainsworth R.
Published: December 2014

In dogs anaesthetized with chloralose, changes in left ventricular systolic pressure were induced using a preparation in which the pressure changes did not distend the aortic arch and in which left atrial and carotid sinus pressures were held constant. The systemic circulation was perfused at constant flow and drained from the venae cavae at constant pressure. An increase in left ventricular systolic pressure caused reflex dilatation of systemic resistance and capacitance vessels as indicated by decreases in arterial perfusion pressure and venous outflow. Responses were obtained when ventricular systolic pressure changed between 16 and 28 kPa (120‐210 mHg). Responses to changes in ventricular pressure were reduced when the carotid sinuses were perfused at high pressures. These results indicate that changes in pressure in the left ventricle result in reflex changes in vascular resistance and capacitance and that responses are obtained to changes in ventricular pressure over a physiological range.
TIME COURSE OF THE CHANGE IN NUCLEAR 3,5,3'‐TRIIODOTHYRONINE RECEPTORS OF SKELETAL MUSCLE IN RELATION TO ENERGY INTAKE
Authors: Geers R. , Ingram D. L. , Dauncey M. J.
Published: December 2014

Nuclear triiodothyronine receptors have been investigated in skeletal muscle from young pigs living at thermal neutrality (26°). Animals were fed at a high (H) or low (L) level of energy intake for 3 or 21 days and killed at 6 or 24 h after the last meal. Receptor numbers were significantly greater on the H than the L intake, even after only 3 days of treatment. The difference in receptors between animals on H and L diets was somewhat less at 6 compared with 24 h after feeding. It is postulated that these changes could be mediated through the action of glucagon.
IN VITRO SPONTANEOUS MOTILITY OF GASTRIC SMOOTH MUSCLES OF THE SHEEP
Authors: Wong M. H. , McLeay L. M.
Published: December 2014

Whole strips of muscle wall cut parallel to their corresponding longitudinal, circular or internal oblique orientations in the reticulum, rumen, omasal body, abomasal body and antrum and to the muscularis mucosae of the omasal leaves were mounted along a vertical axis and their mechanical activities recorded isometrically. The strips were perfused with Tyrode‐Ringer solution at 37 °C bubbled with 100% O2 or a mixture of 95% O2 + 5% CO2. Spontaneous activity was observed in muscle strips from all regions but not all muscle strips were spontaneously active: markedly greater spontaneous activity and a greater sensitivity to stimulatory agents occurred with 100% O2. Spontaneous activity was unaffected by the ganglionic blocking agent hexamethonium (10−5 M) whereas atropine (10−6 M) had no effect, or reduced and in some cases with rumen only, abolished activity. Acetylcholine (10−6‐10−7 M) caused contraction of all muscle except muscularis mucosae from omasal leaves. Electrical stimulation evoked responses which included atropine‐sensitive contractions, relaxations and rebound contraction especially following atropine. The experiments showed that both major muscle layers of the reticulum, rumen, omasum and abomasum in mixed‐layer preparations exhibited spontaneous activity when removed from the influence of their cholinergic innervation and this included atropine‐resistant diphasic contractions of the internal oblique muscle of the reticulum. The muscularis mucosae of the omasal leaves exhibited spontaneous contractile activity unaffected by cholinergic agonists and antagonists.
THIXOTROPY: THE EFFECT OF STIMULATION IN FROG MUSCLE
Authors: Lakie M. , Robson Lesley G.
Published: December 2014

Recent reports have shown that the stiffness of relaxed frog muscle is not a fixed property, but is dependent on the previous history of movement (Lakie & Robson, 1988a). Passive movement decreases stiffness; when the muscle is subsequently allowed to rest it returns at a progressively declining rate to a level of stiffness that is close to its original value (Lakie & Robson, 1988b). We now report that the stiffness of relaxed muscle is also affected by prior tetanic electrical stimulation under isometric conditions. The effect of electrical stimulation is similar to passive movement in that both produce a temporary decrease in stiffness.
FURTHER EVIDENCE FOR A PARATHYROID HORMONE‐RELATED PROTEIN IN FETAL PARATHYROID GLANDS OF SHEEP
Authors: Loveridge N. , Caple I. W. , Rodda C. , Martin T. J. , Care A. D.
Published: December 2014

Extracts of ovine fetal parathyroid glands contained a substance in addition to parathyroid hormone (PTH) which could not be neutralized by antiserum against PTH in a cytochemical bioassay. This substance reacted similarly to human parathyroid hormone‐related protein, the humoral hyper‐calcaemic factor associated with malignancy in man. The ovine fetal PTHrP may be responsible for maintaining the fetus hypercalcaemic relative to the mother.
FAST TO SLOW PHENOTYPIC CHANGES IN RABBIT MUSCLE CAN BE INDUCED WITHOUT INCREASES IN NEURAL ACTIVITY
Authors: Cotter Mary , Cameron Norman , Pattullo Mary
Published: December 2014

Immobilization of rabbit tibialis anterior (fast) musele in a lengthened position for δ weeks led to a fivefold increase in the number of slow oxidative fibres. Unlike the situation in other models of phenotypic change in adult muscle, the increased expression of slow phenotype was not associated with an increase in the level of electrical activation, as monitored in the stretched muscles by chronic telemetric electromyography.
THIXOTROPIC CHANGES IN HUMAN MUSCLE STIFFNESS AND THE EFFECTS OF FATIGUE
Authors: Lakie M. , Robson Lesley G.
Published: December 2014

Quarterly Journal of Experimental Physiology 73 (1988)

Page 490, eqn (3), should read:

Q = 1/c√KJ
THE EFFECTS OF NICKEL ON CONTRACTION AND MEMBRANE CURRENT IN ISOLATED RAT MYOCYTES
Authors: O'Neill S. C. , Valdeolmillos M. , Eisner D. A.
Published: December 2014

Depolarization of isolated myocytes for several seconds produces a maintained, tonic component of tension. We have found that this is abolished by 5 mM‐Ni2+. Furthermore if Ni2+ is applied after the tonic contraction has developed then its relaxation is prevented. These results are consistent with the hypothesis that Ni2+ inhibits Na+‐Ca2+ exchange. Finally, also consistent with an inhibition of Na+‐Ca2+ exchange, Ni2+ abolishes the transient inward current while having no effect on the underlying change of [Ca2+]i.
FACTORS DETERMINING THE DIGESTIVE EFFICIENCY OF THE DOMESTICATED DONKEY (EQUUS ASINUS ASINUS)
Authors: Izraely H. , Choshniak I. , Shkolnik A. , Stevens C. E. , Demment M. W.
Published: December 2014

Factors determining the digestive efficiency of donkeys were studied in animals fed either a low quality roughage (wheat straw: 77·1% neutral detergent fibre, 2·8% crude protein) or a high quality forage (alfalfa hay: 47·5% neutral detergent fibre, 22·7% crude protein). The neutral detergent fibre (NDF) intake when fed wheat straw was 1693 ± 268 g animal−1 day−1, 10% higher than when fed alfalfa hay. Digestive coefficient of NDF and acid detergent fibre (ADF) when fed wheat straw amounted to 50·9 ± 4·9 and 42·0 ± 4·1% respectively. NDF and ADF apparent digestibilities and mean retention times (37·7 ± 1·7 and 36·4 ± 3·2 h respectively) were not significantly different (P 〉 0·05) between the two diets. The donkey appears to digest cell wall constituents as efficiently as the Bedouin goat when on low quality roughage, but less efficiently when fed alfalfa hay. Its energy digestibility is, however, as high as that reported for the Bedouin goat. The donkey's high energy digestibility is related to its capacity to digest soluble food components more efficiently than the ruminant. The mean retention time in the donkey is shorter than in the Bedouin goat and is consistent with its capacity to compensate for a lower quality diet by increasing its intake rate. Recycling of urea in donkeys maintained on wheat straw amounted to 75·5 ± 13·0% of the entry rate. A decrease in the rate of renal urea filtration, coupled with an increase in the fraction reabsorbed, increased the retention of nitrogenous waste and permitted recycling of nitrogen into the gut.
THE EFFECTS OF IONOPHORE A23187 ON PERMEABILITY OF THE FROG MESENTERY MICROVASCULATURE
Authors: Michel C. C. , Phillips Mary E.
Published: December 2014

The effects of the divalent cation ionophore A23187, upon microvascular permeability have been investigated in single perfused capillaries and venules in the mesenteries of pithed frogs. In all experiments, the vessels were perfused with Ringer solutions containing the macromolecules Ficoll 70 (40 mg ml−1) and bovine serum albumin (10 mg ml−1). Hydraulic permeability (Lp) of the vessel walls and the effective osmotic pressure (σΔπ) exerted across them by the perfusate macromolecules were estimated by the method of Michel (1980). In eleven experiments addition of A23187 to the perfusate raised Lp from a mean value (± S.E.M.) of 4·76 (± 1·05) x 10−7 cm s−1 cmH2O−1 to one of 11·97 (± 1·96) x 10−7 cm s−1 cmH2O−1 and reduced σΔπ from a mean (± S.E.M.) of 16·5 (± 2·01) cmH2O to one of 7·6 (± 1·93) cmH2O. The effects of A23187 on Lp and σΔπ were reversible. A23187 was found to increase Lp and reduce σΔπ after the mesentery had been exposed to compound 48/80 to degranulate the mast cells two or more hours previously. A23187 also appeared to be effective in raising Lp and lowering σΔπ in the absence of Ca2+ ions from the perfusate and superfusate. The ionophore was found to reduce permeability, however, when Mg2+ ions were removed from the perfusate and superfusate both in the absence and in the presence of Ca2+. This reduction in permeability could be converted into an increase in Lp and fall in σΔπ if Mg2+ were restored to the superfusate. It is concluded that A23187 increases vascular permeability in a reversible manner and that Mg2+ ions in the extracellular fluids are necessary for its action.
Na+−Ca2+ EXCHANGE IN LIMB MUSCLES OF DYSTROPHIC (C57 BL/6J dy2J/dy2J) MICE
Authors: Noireaud J. , Léoty C.
Published: December 2014

Isometric tension of Na+‐withdrawal contractures, membrane potential and intracellular Na+ activity (aiNa) have been measured in vitro under conditions which modify the activity of the Na+−Ca2+ exchanger of dystrophic limb muscles of (dy2J/dy2J) C57 BL/6J mice. In dystrophic soleus (Sol) and extensor digitorum longus (EDL) muscles exposed to Na+‐free medium, there was a decrease in aiNa associated with a hyperpolarization of the membrane and the generation of a transient contracture. By contrast, exposing normal or denervated EDL muscles to Na+‐free solution induced no change in aiNa nor in the resting tension. This study shows that Na+−Ca2+ exchange is still present in dystrophic Sol muscle. However from thermodynamic considerations, it could be suggested that the higher resting aiNa compared with that in normal muscle, may decrease the efficacy of the exchange.
THE ROLE OF GASTRIN IN THE DEVELOPMENT OF THE GASTROINTESTINAL TRACT IN FETAL SHEEP
Authors: Avila C. G. , Robinson P. M. , Harding R. , Young I. R.
Published: December 2014

We have investigated the role of gastrin in the development of the gastrointestinal tract during the latter part of gestation in fetal sheep. We surgically removed the major source of gastrin, the gastric (abomasal) antrum, from five fetuses at 90 days of gestation. The remaining abomasum was anastomosed to the pylorus allowing unobstructed flow of luminal contents. Another five fetuses, subjected to sham‐antrectomies at 90 days, served as controls. Further surgery was performed in all fetuses at 120 days for the placement of vascular catheters to permit measurement of plasma gastrin concentrations. The fetuses were infused with [3H]thymidine to study villus cell migration rates. At 135 days of gestation samples of gastric (abomasal) fundus, and proximal and distal small intestine, were processed for histology and morphometric analysis. The antrectomized fetuses had significantly lowered plasma gastrin concentrations (P 〈 0·025) between 120 and 135 days. At 135 days, the mean body weight, crown‐rump length, total gut weight and small intestinal weight and length were not significantly different between the two groups. Similarly, tlire were no significant differences between groups in the mean thicknesses of the gut wall, mucosa and muscularis externa, or in the mean villus height and crypt depth in the proximal or distal parts of the small intestine. Villus cell migration rate in the proximal and distal small intestine was not affected by antrectomy. No simple relationship could be demonstrated between any of these parameters and plasma gastrin concentration. In the antrectomized fetuses, the mean crypt density and crypt‐to‐villus ratio were significantly reduced in the proximal small intestine (P 〈 0·05), while only the density of villi was reduced in the distal small intestine (P 〈 0·05). In the antrectomized fetuses there were significant correlations between plasma gastrin and the fraction of fundic mucosa occupied by gland and pit (P 〈 0·005), and between plasma gastrin concentration and villus density (P 〈 0·01) and crypt‐to‐villus ratio (P 〈 0·025) in the proximal small intestine. In the sham group these correlations were absent. We conclude that the removal of the gastric antrum in fetal sheep results in decreased plasma gastrin concentration, and that gastrin appears to have a regulatory or trophic role on the gut mucosa in these circumstances. During normal development, however, gastrin does not seem to exert this effect, suggesting either that antrectomy removes a factor which is inhibitory or regulatory of gastrin or that the remaining forms of circulating gastrin have a different effect on the mucosa than antral gastrin.
MICROANGIOGRAPHIC INVESTIGATION OF THE EFFECTS OF RADIOGRAPHIC CONTRAST MEDIA AND HYPERKALAEMIA ON CORONARY ARTERY CALIBRE IN THE RABBIT
Authors: Flores Nicholas A. , Sheridan Desmond J. , Davies Robert Ll.
Published: December 2014

A microangiographic technique, using novel methods of contact X‐ray microscopy, was developed and used to study the effects of ionic (Urografin 370) and non‐ionic (Omnipaque 350) radiographic contrast media, and hyperkalaemia (exposure to 15, 30 and 60 mM‐K+ solutions) on coronary artery calibre and total coronary vascular resistance in isolated, Langendorff‐perfused rabbit hearts. Repeated injection of both types of contrast media produced similar haemodynamic effects and some reduction in coronary diameter, but greater variation in arterial calibre was observed with Urografin (P 〈 0·001). Perfusion with hyperkalaemic solutions produced a dose‐related increase in total coronary vascular resistance (P 〈 0·001), but this was associated with a complex pattern of changes in large‐vessel calibre. The direction and magnitude of the responses to hyperkalaemia varied depending on the site within the artery studied; in general hyperkalaemia produced a dose‐related vasoconstriction which was greater distally than proximally. Thus, with 15 mM‐K+ vasoconstriction occurred in the left anterior descending artery (4·3% proximally; 15·6% distally) which increased to 40·7 and 52·1% (proximally and distally, respectively) with 30 mM‐K+. With 60 mM‐K+ further diffuse and segmental vasoconstriction occurred in 4/5 and 1/5 hearts respectively (mean values 31·5 and 56·7% at the proximal and distal sites). During perfusion with 15 mM‐K+, net vasodilatation (17% at both the proximal and distal sites) was noted in the left ventricular branch of the circumflex artery, but with 30 mM‐K+ vasoconstriction (18·3% proximally and 38·0% distally) occurred. Thus, while hyperkalaemia consistently increased coronary vascular resistance, these changes were associated with marked variation in the extent and distribution of in situ constriction and dilatation within the coronary circulation.
SARCOMERE ‘GIVE’ DURING STRETCH OF FROG SINGLE MUSCLE FIBRES WITH ADDED SERIES COMPLIANCE
Authors: Bottinelli R. , Eastwood J. C. , Flitney F. W.
Published: December 2014

Stretch of active whole muscle causes a sudden yielding of the sarcomeres when the actin and myosin filaments are displaced by 10‐12 nm from their isometric position. This behaviour is not normally seen during stretch of singly‐dissected fibres, but it can be induced by introducing series compliance into the system.
THE INFLUENCE OF BLOOD FLOW RATE ON ADENOSINE RELEASE FROM CONTRACTING DOG SKELETAL MUSCLE
Authors: Ballard H. J. , Cotterrell D. , Karim F.
Published: December 2014

The dependence of adenosine release on blood flow was investigated in greyhounds anaesthesized with sodium pentobarbitone and artificially ventilated. The gracilis muscles were neurally and vascularly isolated, and perfused at constant flow rates of 42% (low), 89% (medium) or 132% (high) of their maximum free flow during contraction induced by stimulation of the motor nerve. Stimulation produced contractions whose force declined from 716 ± 60 to 464 ± 46 g (100 g)−1 over 10 min. Resting perfusion pressure increased in line with the flow rate, but the fall in resistance accompanying contractions varied reciprocally with the flow (57 ± 2·9, 39·6 ± 6·6 and 15·3 ± 5·6% at low, medium and high flows respectively). Venous PO2 decreased during contraction to 26·6 ± 6·2 mmHg at ‘low’, 31·5 ± 5·1 mmHg at ‘medium’ and 37·2 ± 1·7 mmHg at ‘high’ flows. Venous plasma adenosine concentration increased significantly above resting levels during contraction at all flow rates. Adenosine release at low flow (12·0 ± 2·7 nmol min−1 (100 g)−1) was significantly greater than that at medium or high flows (5·6 ± 1·3 and 4·1 ± 1·3 nmol min−1 (100g)−1 respectively), but the latter were not different from each other. There was no correlation between adenosine release and either venous oxygen tension during muscle contraction or the ratio of oxygen supply to free‐flow oxygen consumption. These data suggest that the mechanism underlying adenosine release during muscle contraction may be independent of oxygen lack.
PHYSIOLOGICAL CHANGES IN SKELETAL MUSCLE AS A RESULT OF STRENGTH TRAINING
Authors: Jones D. A. , Rutherford O. M. , Parker D. F.
Published: December 2014

The picture of training that emerges is of a process that can be divided into a number of phases. In the first phase there is a rapid improvement in the ability to perform the training exercise such as lifting weights which is the result of a learning process in which the correct sequence of muscle contractions is laid down as a motor pattern in the central nervous system. This phase is associated with little or no increase in the size or strength of individual muscles. The learning process appears to be very specific in that lifting weights makes better weight lifters but not better sprinters. The second phase is an increase in the strength of individual muscles which occurs without a matching increase in the anatomical cross‐section. The mechanism for this is not clear but could be a result of increased neural activation or some change in the fibre arrangement or connective tissue content. The third phase starts at a point where scientific studies usually end, at about 12 weeks when non‐athletic subjects are beginning to tire of the repeated training and testing. After this point, if training continues, there is probably a slow but steady increase in both size and strength of the exercised muscles. The stimulus for these changes remains enigmatic but almost certainly involves high forces in the muscle, probably to induce some form of damage that promotes division of satellite cells and their incorporation into existing muscle fibres. Our information on the effect of long‐term training comes primarily from observations on elite athletes whose physique may well be the result of genetic endowment or the use or abuse of drugs. For the athlete or patient hoping to increase muscle size by weight training the best combination of intensity, frequency and type of exercise still remains a matter of individual choice rather than a scientific certainty.