bluuebunny/crossref_metadata_2025 huggingface dataset:
Pancreatic acinar cells: membrane potential and resistance change evoked by acetylcholine
Authors: Nishiyama A. , Petersen O. H.
Published: December 2014

1. Membrane potential and input resistance measurements were made on segments of pancreas from mice or rats, whereas potential measurements alone were made on pancreas from cats or rabbits placed in a tissue bath which was perfused with a Krebs—Henseleit solution.

2. The acinar cell membrane potential was about −40 mV and the input resistance 4–8 MΩ. Spontaneous miniature depolarization potentials were occasionally observed superimposed upon the resting potential. In these cases synchronous reductions in input resistance were observed.

3. The immediate effect of stimulation with ACh was always a depolarization and a concomitant reduction in input resistance and time constant. In some cases a secondary depolarization was observed accompanied by an increase in input resistance. The time constant, however, remained as short as in the first phase of depolarization.

4. In the rabbit pancreas ACh evoked biphasic potential changes: depolarization followed by hyperpolarization. A similar pattern could sometimes also be observed in the mouse pancreas following a brief pulse of ACh addition. In these cases the depolarization was followed by a small but relatively long lasting hyperpolarization. The depolarization was accompanied by a reduction in input resistance.

5. Pancreozymin caused depolarization of the acinar cell membrane and a marked reduction in input resistance and time constant.

6. In the presence of atropine (1·4 × 10−6
M) depolarization of the acinar cell membrane by an elevated K concentration (50 m
M) in the bathing fluid did not reduce the input resistance.

7. It is concluded that the two physiological stimulants of pancreatic protein secretion, ACh and pancreozymin, act on the acinar cells by increasing the permeability of the plasma membrane.
The importance of central adrenergic neurones in renal hypertension in rabbits
Authors: Chalmers J. P. , Dollery C. T. , Lewis P. J. , Reid J. L.
Published: December 2014

1. Central nervous system adrenergic neurones were partially destroyed by injection of 6‐hydroxydopamine (6‐OHD) into the cisterna magna of normal rabbits and of rabbits with renal hypertension produced by bilateral wrapping of the kidneys with cellophane.

2. Six weeks after renal manipulation, the mean arterial pressure of control animals was 122·1 ± 2·4 mmHg while the pressure of rabbits which had been pre‐treated with intracisternal 6‐OHD was only 100·0 ± 4·3 mmHg.

3. Partial destruction of central adrenergic neurones by injection of 6‐OHD into the cisterna magna produced a sustained lowering of arterial pressure in rabbits with established renal hypertension, whether this hypertension had been short (6 weeks) or of long duration (18 weeks).

4. Adrenergic neurones in the central nervous system play a role in the development and maintenance of the raised arterial pressure in rabbits with renal hypertension.
The ultrastructure of the carotid body in chronically hypoxic rabbits
Authors: Møller M. , Møllgård K. , Sørensen S. C.
Published: December 2014

1. The ultrastructure of the carotid body in the rabbit has been examined by electron microscopy.

2. A comparison was made between the ultrastructure of the carotid bodies in sea level rabbits, in rabbits which had been exposed to hypoxia equivalent to an altitude of 6000 m for 7 days and in rabbits which always had lived at an altitude of 4000–4300 m.

3. We could not detect any difference in the ultrastructure between the two groups of hypoxic rabbits.

4. When the hypoxic rabbits were compared with sea level rabbits there was a marked increase in the number of dense cored vesicles and mitochondria in the type I cells in the hypoxic rabbits. The Golgi region also appeared to be enlarged in the type I cells in the hypoxic rabbits.

5. The finding suggests that in the rabbit the production of amines, probably dopamine, within the type I cells is increased during prolonged hypoxia which might explain the lowered ventilatory response to hypoxia observed in human high altitude residents.

6. If the carotid bodies are organs of internal secretion the finding is compatible with an increased production of a hormone produced within the type I cells.
Extracellular space in some isolated tissues
Authors: McIver D. J. L. , Macknight A. D. C.
Published: December 2014

1. The spaces occupied by isotopically labelled inulin, polyethylene glycol, mol. wt. 4000 (PEG 4000), polyethylene glycol, mol. wt. 1000 (PEG 1000) and sucrose in metabolizing mammalian kidney and liver slices and in toad bladder epithelial cell preparations incubated in vitro have been examined.

2. In slices of mammalian tissue, and in homogenized liver, it proved impossible to extract inulin completely from tissue which had been dried. However, inulin was recovered as completely from both dried and undried toad bladder epithelial cells scraped from hemibladders incubated in vitro.

3. PEG 4000 occupied a space in all preparations similar to that from which inulin was extracted in dried tissue.

4. PEG 1000 and sucrose entered cellular water in mammalian slices, but PEG 1000 occupied a similar space to inulin in toad bladder epithelial cell preparations.

6. It is concluded that inulin enters cellular water in mammalian slices from which after drying of the slices it cannot be extracted. It thus rather fortuitously provides a measure of extracellular water under these conditions. In preparations of toad bladder epithelial cells inulin seems to be a satisfactory extracellular marker. PEG 4000, which did not appear to enter cellular water also allows a reasonable estimate of extracellular water. PEG 1000 is a suitable extracellular marker for toad bladder epithelial cell preparations but not for mammalian slices. Sucrose entered cellular water in both slices and toad bladder epithelial cells and is not a satisfactory extracellular marker in these tissues.
Kinetic analysis of the delayed outward currents in frog atrium. Existence of two types of preparation
Authors: Ojeda Carlos , Rougier Oger
Published: December 2014

1. The outward currents underlying delayed rectification have been studied in frog auricular trabeculae with the double sucrose gap method.

2. The results obtained in our experimental conditions allow us to discard the hypothesis of an accumulation of ions during the flow of the outward current.

3. In most of the cases the delayed current is composed of two components similar to those previously described by Noble & Tsien (1969a, b).

4. The first component I1 is activated with a time constant of about 0·3 sec at the resting potential (E = − 70 mV) and of about 0·75 sec at E = − 5 mV. The steady‐state value of the degree of activation (x1)∞ varies from 0 at E = − 90 mV to 1 at E = + 20 mV. The reversal potential is near E = − 80 mV; this current seems to be mainly carried by potassium ions.

5. The second component I2 is very slowly activated, with a time constant of 3·5 sec at E = − 70 mV and of 5 sec at E = − 5 mV. The steady‐state value of the degree of activation (x2)∞ varies from 0 at E = −40 mV to 1 at E = + 25 mV. The reversal potential is near E = −60 mV; this current is less specific than the first component.

6. In some preparations the delayed current is composed of only one component. This current is activated with a time constant of 0·6 sec at the resting potential and of 1·5 sec at E = −5 mV. The steady‐state value of the degree of activation is 0 at E = −90 mV and 1 at E = + 30 mV. The reversal potential is between E = −70 and E = −60 mV.

7. The role of these currents in the processes of repolarization of normal and prolonged action potentials, and in the pace‐making activity is discussed.
Correlation of the directly observed responses of mesenteric vessels of the rat to nerve stimulation and noradrenaline with the distribution of adrenergic nerves
Authors: Furness J. B. , Marshall Janice M.
Published: December 2014

1. The effects of nerve stimulation and of the topical application of noradrenaline on arteries, capillaries and veins of the mesentery of the anaesthetized rat were examined by direct observation under a microscope. The distribution of adrenergic nerves to the vessels of the mesentery was studied using the fluorescence histochemical method.

2. Principal arteries, small arteries and terminal arterioles were all innervated by a network of adrenergic fibres and they all constricted in response to the stimulation of paravascular nerves and to exogenous noradrenaline. Few adrenergic fibres accompanied the smaller, precapillary arterioles; these vessels did not respond to nerve stimulation, although they were constricted by concentrations of noradrenaline as low as 10−10 g/ml.

3. The capillaries did not respond to nerve stimulation or to applied noradrenaline. All veins were constricted by noradrenaline, but only those veins greater than about 30 μm in internal diameter responded to nerve stimulation.

4. At stimulus frequencies greater than 4 Hz the flow of blood through the microvasculature usually ceased, although there was never complete closure of these vessels. The maximum constriction observed in principal arteries was usually between 50 and 70% of the control internal diameter, and in small arteries and terminal arterioles was between 40 and 65% of the control internal diameter.

5. It is concluded that the principal arteries and small arteries of the mesenteric vasculature are important in the control of blood flow through this vascular bed during sympathetic stimulation and following topical application of noradrenaline, and that the precapillary arterioles are important vessels determining the rate of blood flow through the capillary bed under resting conditions.
Effects of dopamine on the superior cervical ganglion of the rabbit
Authors: Dun N. , Nishi S.
Published: December 2014

1. The effects of dopamine on isolated rabbit superior cervical ganglion were investigated with intracellular recording techniques.

2. Dopamine (10−5‐10−3
M) depressed the amplitude of the excitatory post‐synaptic potential (e.p.s.p.) and blocked impulse transmission.

3. Dopamine (10−4
M) induced a slight (2–5 mV) post‐synaptic hyperpolarization without altering membrane conductance.

4. The post‐synaptic membrane sensitivity to acetylcholine (ACh) applied iontophoretically was not affected by dopamine.

5. Dopamine decreased the frequency of miniature excitatory post‐synaptic potentials (m.e.p.s.p.s) in a high K+ solution, with no change in the amplitude of m.e.p.s.p.s.

6. Dopamine reduced the quantal content of the e.p.s.p. in a low Ca2+ and high Mg2+ solution, but had no effect on the quantal size.

7. The ganglionic blocking effect of dopamine was antagonized by phenoxybenzamine, but not by propranolol.

8. The results show that the ganglionic depressant effect of dopamine is exerted primarily through an alpha‐adrenoceptive site at the presynaptic nerve terminal.
Stimulation electrically and by acetylcholine of the rat hypothalamus in vitro
Authors: Bradbury M. W. B. , Burden Janet , Hillhouse E. W. , Jones M. T.
Published: December 2014

1. The hypophysiotrophic area of the rat hypothalamus was studied in vitro. The preparation remained viable for at least 3 hr and showed oxygen consumption varying between 68·9–120 μmole/g.hr. The tissue potassium ion content (per unit wet weight) fell to about 50% of the in vivo concentration during this time compared with 15% in the presence of ouabain (10−4 M). Histological examination of tissue incubated for 3 hr showed variable perineuronal oedema but the nuclei were of normal appearance and none showed the pyknotic changes that would be associated with cell degeneration.

2. Corticotrophin releasing hormone (CRH) in the medium pooled from five to twenty hypothalami was assayed in five to twelve rats which were median‐eminence lesioned 48 hr earlier. In vitro corticosterone production of quartered adrenals was used as the end point of the assay. Regression lines of the dose—response curves for ACTH, crude CRH and different volumes of medium from electrically stimulated hypothalami were parallel. CRH output was maximal at 75 Hz and 100 μA when the square‐wave pulses lasted for 1 msec. No CRH activity was found on stimulation of cerebral cortex or thalamic tissue pieces of equivalent size.

3. Hypothalami taken from rats, adrenalectomized 7–14 days previously, released several‐fold more CRH into the medium during electrical stimulation than the initial content of the tissue, showing that the tissue was capable of synthesizing CRH in vitro. The hypothalami taken from intact rats released considerably less CRH into the medium than tissue taken from 12 to 14 day adrenalectomized rats. The hyper‐secretion of CRH observed in hypothalami taken from adrenalectomized rats was abolished by pre‐treatment with 5 mg/100 g s.c. of corticosterone 24 hr before removal of the tissue. It is therefore proposed that the delayed negative feed‐back action of corticosterone at the hypothalamic level is by the suppression of CRH synthesis and that the effect of secretion is secondary to the effect on synthesis.

4. The presence of Ca2+ in the medium was essential for the release of CRH.

5. CRH secretion increases linearly with doses of acetylcholine from 5·5 × 10−15‐5·5 × 10−14 M. Cerebral cortex incubated with acetylcholine showed no CRH activity. The effect of acetylcholine was reduced by atropine (3·5 × 10−13 M). Median eminence‐pituitary stalk fragments (which contain mainly terminal axons of neurones) incubated with acetylcholine showed no CRH stimulation in the doses that activate the release of CRH using the hypophysiotrophic hypothalamus. Acetylcholine may act as a neurotransmitter at the dendritic level in the CRH neurone.
Afferent fibres from pulmonary arterial baroreceptors in the left cardiac sympathetic nerve of the cat
Authors: Nishi K. , Sakanashi M. , Takenaka F.
Published: December 2014

1. Afferent discharges were recorded from the left cardiac sympathetic nerve or the third sympathetic ramus communicans of anaesthetized cats. Twenty‐one single units with baroreceptor activity were obtained.

2. The receptors of each unit were localized to the extrapulmonary part of the pulmonary artery, determined by direct mechanical probing of the wall of the pulmonary artery after death of the animals. Conduction velocity of the fibres ranged from 2·5 to 15·7 m/sec.

3. Afferent discharges occurred irregularly under artificial ventilation. The impulse activity was increased when pulmonary arterial pressure was raised by an intravenous infusion of Locke solution, or by occlusion of lung roots, and decreased by bleeding the animal from the femoral artery.

4. Above a threshold pressure, discharges occurred synchronously with the systolic pressure pulse in the pulmonary artery. A progressive further rise in pressure did not produce an increase in the number of impulses per heart beat. Occlusion of lung roots initially elicited a burst of discharges but the number of impulses for each cardiac cycle gradually decreased.

5. The receptors responded to repetitive mechanical stimuli up to a frequency of 10/sec, but failed to respond to stimuli delivered at 20/sec.

6. The results provide further evidence for the presence of afferent fibres in the cardiac sympathetic nerve. These afferent fibres are likely to provide the spinal cord with specific information only on transient changes in pulmonary arterial pressure.
The binding of tetrodotoxin and α‐bungarotoxin to normal and denervated mammalian muscle
Authors: Colquhoun D. , Rang H. P. , Ritchie J. M.
Published: December 2014

1. The binding of [3H]tetrodotoxin and [125I]iodo‐α‐bungarotoxin to innervated and denervated rat diaphragm muscle has been measured.

2. A saturable component of tetrodotoxin binding, which was inhibited by saxitoxin, was detected in addition to considerable non‐saturable binding. The saturable component had an equilibrium constant of K = 6·1 n
M (limits 4·7–7·8 n
M) and binding capacity M = 2·5 f‐mole/mg wet wt. (limits 2·1–2·8 f‐mole/mg).

3. If the saturable component consisted of one‐to‐one binding of tetrodotoxin to sodium channels, the density of sodium channels would be about 21/μm2 of surface membrane, a figure similar to that found in other excitable membranes.

4. After denervation the specific tetrodotoxin binding, as measured by the ratio M/K, fell by a factor of 2·8. This change appeared to be due to a fall in binding capacity rather than a decrease in affinity.

5. After denervation the maximum rate of rise of the action potential fell by 27% and became partially resistant to tetrodotoxin. The maximum rate of rise was at first reduced by tetrodotoxin in similar concentrations to those affecting normal muscle, but even large concentrations which completely blocked normal muscle only reduced the maximum rate of rise by a factor of about 2.

6. Detubulation with glycerol did not appreciably affect the tetrodotoxin sensitivity of normal or denervated muscle.

7. Tetrodotoxin resistance was not observed after denervation of the frog sartorius muscle.

8. [125I]iodo‐α‐bungarotoxin binding amounted to 3·8 ± 0·7 f‐mole/mg in innervated muscle and 44·5 ± 2·1 f‐mole/mg in denervated muscle. Most of the uptake was inhibitable by (+)‐tubocurarine.

9. The increase in the labelled bungarotoxin binding is much larger than the specific tetrodotoxin binding of innervated muscle, which renders implausible the possibility that the acetylcholine receptors which appear after denervation are related to the tetrodotoxin resistant‐sodium channels.
Brisk and sluggish concentrically organized ganglion cells in the cat's retina
Authors: Cleland B. G. , Levick W. R.
Published: December 2014

1. Nine hundred and sixty cat retinal ganglion cells were evaluated with respect to receptive‐field organization and latency to antidromic activation of their axons from optic‐tract and mid‐brain positions.

2. The vast majority (92%) had the familiar concentric centre/surround organization. As in earlier work these could be classed as sustained or transient, independently of the centre type. About 13% of the concentric cells were characterized by relatively sluggish responses to conventional visual stimuli which yielded brisk responses from the others. The sluggish cells constituted a previously unspecified class of concentric receptive fields.

3. The responses of brisk and sluggish cells to a variety of stimuli were described with a view to developing procedures for distinguishing them on functional grounds.

4. Measurements of latency to antidromic activation of retinal axons confirmed earlier work in showing that cells classed as brisk‐transient had the shortest conduction times from the optic tract. Cells classed as brisk‐sustained had intermediate conduction times and from earlier work would constitute an important input to the lateral geniculate nucleus. A proportion of the brisk‐sustained axons reached the pretectal region (especially on‐centre types) and a small minority reached the superior colliculus (especially off‐centre types).

5. Sluggish cells had generally slower antidromic conduction times; despite some overlap with the brisk‐sustained class, the slower conduction provided independent support for the functional differentiation. Sluggish axons reached the pretectal region and superior colliculus.

6. The brisk‐sustained cells constituted the majority of the recordings in the area centralis.

7. A comparison with the morphological data of Boycott & Wässle is made which suggests that the brisk‐transient units corresponded with α cells, the brisk‐sustained with β cells, and the sluggish units were included amongst the γ cells.
The entry of labelled calcium into the innervated region of the mouse diaphragm muscle
Authors: Evans R. H.
Published: December 2014

1. A method is described for measuring the distribution of 45Ca between the junctional and non‐junctional regions of the mouse diaphragm muscle.

2. Muscles which were incubated in Ringer solution containing labelled calcium accumulated the tracer at the junctional region when acetylcholine or carbachol was present. Denervation did not prevent this accumulation at the normally innervated region.

3. Histochemical evidence indicated that, in the presence of acetylcholine or carbachol, calcium entered diaphragm muscle fibres at the junctional region.

4. Accumulation of calcium occurred at all regions of muscle fibres depolarized by potassium. In the presence of acetylcholine or carbachol, accumulation occurred at the junctional region in the absence of muscle fibre post‐junctional membrane depolarization.

5. It is suggested that the desensitized muscle fibre post‐junctional membrane has an increased calcium permeability.
The circadian rhythms of human subjects without timepieces or indication of the alternation of day and night
Authors: Mills J. N. , Minors D. S. , Waterhouse J. M.
Published: December 2014

1. Seven solitary subjects, and two groups of four, spent from 5 to 13 days in an isolation unit without knowledge of time. Three solitary subjects and one group of four adopted fairly regular activity habits with a period of 25–27 h; one subject adopted a period of 30 h, and one of 27 h initially, decreasing to 24–25 h after a few days. One group of four awoke roughly every 24 h, after a sleep which was alternately about 8 h, or about 4 h and believed by the subjects to be an afternoon siesta. Two solitary subjects alternated sleeps of about 8 or 16 h, separated by 24 h of activity.

2. Deep temperature in all subjects oscillated with a period of 24–26 h, which was thus commonly distinct from their activity habits.

3. Urinary potassium followed a rhythm whose period, though usually close to, was sometimes distinct from, that of temperature. A secondary period corresponding to that of activity was also sometimes present.

4. Urinary sodium and chloride usually gave evidence of two periodic components, one corresponding to activity and the other to the rhythm of either temperature or of urinary potassium.

5. Urinary creatinine and phosphate usually followed the subject's routine of activity.

6. Plasma samples were collected on a few occasions and analysed for phosphate and 11–hydroxycorticosteroids. Changes in plasma phosphate were usually, but not always, associated with similar changes in urinary phosphate, and changes in plasma corticosteroids were often, but not always, associated with similar changes in urinary potassium shortly afterwards.

7. Observations are recorded on a subject alone in a cave for 127 days. His activity habits, though wildly variable, gave evidence of a period of 25·1 h and his urinary electrolyte excretion indicated a shorter period, of 24·6 h. During the following 3 days, when he remained in the cave but was visited frequently, his plasma corticosteroids and urinary potassium oscillated with a period of 16 h.

8. The possible mechanisms controlling these rhythms are discussed.
Inward movement of sodium ions in resting and stimulated frog's sartorius muscle
Authors: Venosa R. A.
Published: December 2014

1. Paired frog sartorius muscles were exposed to Ringer solutions labelled with 22Na+ for about 20 min. At the end of this exposure one of them was stimulated supramaximally one hundred to two hundred times. Immediately after the stimulation both members of the pair were washed in a series of tubes filled with a Na+‐free medium containing 3 × 10−5
M strophanthidin.

2. Under the above conditions the intracellular component of the efflux was exponential with an average time constant (τ) of 388 min, that is, approximately four times longer than in the presence of normal Ringer. On the other hand the mean τ for the washout of the interfibre space was 3·2 min.

3. From the extrapolation to time zero of the intracellular component of the washout curve the initial intracellular radioactivity of both muscles was obtained and the resting and extra Na+ influx were calculated.

4. The mean surface membrane area/muscle weight ratio was found to be 552 cm2.g−1 and the mean fibre diameter 53·4 μm for muscles weighing on the average 60 mg.

5. The average resting Na+ influx in the presence of normal Ringer was 4·7 p‐mole.cm−2.sec−1. As the external Na+ concentration ([Na+]0) was reduced the Na+ influx diminished in a non‐linear fashion. This non‐linearity could be accounted for by the presence in the influx of a Na+ for Na+ exchange fraction which saturates at low [Na+]0.

6. The mean extra Na+ influx in the presence of normal Ringer was 27·4 p‐mole.cm−2.impulse−1 and was not significantly affected either by halving [Na+]0 or by varying the frequency of stimulation. When [Na+]0 was reduced to 45 m
M by partial replacement of Na+ by Tris+ the extra influx was significantly higher than when choline+ instead of Tris+ was used to substitute for Na+.
Evidence for the involvement in the baroreceptor reflex of a descending inhibitory pathway
Authors: Coote J. H. , Macleod Valerie H.
Published: December 2014

1. The onset and time course of baroreceptor inhibition of pre‐ and post‐ganglionic sympathetic reflex activity has been examined in the anaesthetized cat.

2. The shortest time to the onset of inhibition of an intercostal evoked reflex response in cardiac and renal nerve was less than 90 msec following a rise in pressure in a carotid sinus blind sac, and around 55 msec following stimulation of the ipsilateral sinus nerve. The cardiac nerve response was completely inhibited before the renal nerve response.

3. Because of the long delays in the somato‐sympathetic reflex pathway it is argued that these minimum times will be much less than the real central delay of baroreceptor inhibition. These were estimated by adding on the central times for the somato‐sympathetic reflexes to give latencies of 94–143 msec for the inhibition.

4. A spinal sympathetic reflex was inhibited by 30–75% following a rise in pressure in a carotid sinus blind sac or sinus nerve stimulation. The minimum time for this inhibition was around 100 msec.

5. The baroreceptor inhibition of the spinal sympathetic reflex was abolished following section of a restricted region in the dorsolateral part of the lateral funiculus of the cervical spinal cord.

6. Both pre‐ and post‐ganglionic reflexes could be inhibited when stimulating within three regions of the medulla oblongata. The latency to inhibition elicited from the ventromedial reticular formation was short, some 5‐30 msec, whereas that elicited from a ventrolateral region or the mid line raphe nucleus was long, some 90–160 msec.

7. The possibility is discussed that the baroreceptor inhibition of both the pre‐ and post‐ganglionic reflexes examined in this study is occurring at the spinal level via a pathway from either the raphe nuclei or ventrolateral medulla.
Renin and angiotensin‐like levels in foetal, new‐born and adult sheep
Authors: Pipkin Fiona Broughton , Kirkpatrick S. Margaret L. , Lumbers Eugenie R. , Mott Joan C.
Published: December 2014

1. Plasma renin (measured as rate of formation of angiotensin I ng/ml.hr−1 in the presence of added substrate at pH 7·5 and 37° C) was much lower in recently nephrectomized foetal, new‐born and older lambs than in intact siblings or other similar lambs.

2. Angiotensin II‐like concentrations were measured using a superfusion technique in an extracorporeal circuit. Resting concentrations in acute experiments under anaesthesia were deduced by comparison of carotid blood of intact lambs with that from recently nephrectomized lambs.

3. Angiotensin II‐like activity (mean ±
S.E. of mean, 315 ± 117 pg/ml.) was readily detectable in foetal blood at 123–138 days gestation. The highest concentrations (mean ±
S.E. of mean 839 ± 96 pg/ml.) were found in lambs less than 8 hr old, delivered vaginally. The lowest concentrations of angiotensin II‐like activity occurred in lambs delivered by Caesarean section (mean ±
S.E. of mean < 123 ± 12 pg/ml.). Concentrations declined with post‐natal age.

4. Hypovolaemia as a result of haemorrhage evoked an increase in angiotensin II‐like concentrations in foetus, new‐born lambs and adult sheep. The greatest increase of angiotensin‐like concentrations was seen in new‐born lambs. This rise was associated with increase of plasma renin.

5. The rise of arterial pressure during bilateral carotid occlusion in new‐born lambs was accompanied by an increase of angiotensin II‐like concentration.

6. It is concluded that the renin‐angiotensin system is functional and can be stimulated during intra‐uterine life. The increase of angiotensin II‐like concentration following parturition is probably transient and associated with the trauma of delivery. This contrasts with observations made in the rabbit which suggest that full functional maturity of the renin angiotensin system is delayed until the second week of life.
Circulatory effects of deep inspirations, blocked expirations and positive pressure inflations at equal transpulmonary pressures in conscious dogs
Authors: Charlier André A. , Jaumin Pierre M. , Pouleur Hubert
Published: December 2014

1. Circulatory effects of deep inspirations, blocked expirations and constant endotracheal positive pressure inflations were studied in six conscious dogs under comparable geometries of the pulmonary vascular bed, i.e. at equal transpulmonary pressures (around 10·2 cm H2O) and similar lung volumes.

2. In order to characterize these effects, we measured beat‐by‐beat left and right ventricular ejections, pulmonary arterial, left atrial and aortic mean transmural pressures, and concomitant intrathoracic and tracheal pressures. Changes in pulmonary—left heart blood volume were also computed.

3. During inspiration when intrathoracic pressure became more negative, there was a slight increase in right ventricular output (+15%; P < 0·1) and always a net decrease in left ventricular output (−25%; P < 0·01) despite a significant increase in mean transmural left atrial pressure (+3 cm H2O, i.e. +40%; P < 0·005). It is concluded that the more negative intrathoracic pressure increases the left ventricular outflow impedance and that an inspiratory increase in pulmonary vascular capacity cannot explain the observed reduction in left ventricular output since this reduction occurs together with an increase in left ventricular filling pressure.

4. During blocked expiration when intrathoracic pressure was positive, decreases in right ventricular output (−17%; P < 0·05) and in pulmonary‐left heart blood volume (−12 ml.; P < 0·05) were observed while right ventricular outflow impedance increased. After an initial augmentation in left ventricular output (despite a concomitant progressive decrease in mean transmural left atrial pressure), left ventricular output also decreased (−17%; P < 0·05). Such circulatory changes were similar but less marked than those observed under constant positive pressure inflations. These observations suggest that the decrease in venous return (and consequently in right ventricular output) following the increase in intrathoracic pressure is the leading factor which overshadows the augmentation in left ventricular output associated with the simultaneous decrease in left ventricular outflow impedance.

5. Similar experiments performed on two additional dogs in acute conditions showed the same circulatory effects before and after pharmacological blockade. These observations therefore confirm that mechanical factors play a leading part during these respiratory manoeuvres.
A microinjection study of the control of antidiuretic hormone release by the supraoptic nucleus of the hypothalamus in the cat
Authors: Milton A. S. , Paterson Anna T.
Published: December 2014

1. The release of antidiuretic hormone (ADH) has been studied in the chloralose anaesthetized cat after microinjection of various agents directly into the brain, in particular the supraoptic nucleus of the hypothalamus (SON). The concentration of ADH in jugular venous blood was determined using the waterloaded, alcohol anaesthetized rat assay. The position of the microinjection cannula was located post mortem in stained brain sections.

2. Nicotine, noradrenaline (NA) and hypertonic saline caused release of ADH, whereas microinjections of isotonic saline did not affect the blood level of the hormone.

3. Nicotine administered to other sites in the central nervous system (
C.N.S.) could also cause ADH release. Hypertonic saline proved to be an ineffective stimulus at all the tested sites outside the supraoptic region.

4. The ganglion‐blocking agents hexamethonium and pempidine inhibited the releasing action of nicotine at the SON in most of the experiments. These blocking drugs had no effect on osmotic release. When administered alone, both hexamethonium and pempidine had variable, but analogous effects on the hormone output.

5. The α‐adrenoreceptor blocking drug, phentolamine, stimulated ADH release, but the β‐receptor blocking drug, propranolol, had no such effect. Both drugs appeared to have inhibitory action on noradrenergic release of ADH, but neither had a consistent effect on the osmotic release of the hormone.
Role of cations, anions and carbonic anhydrase in fluid transport across rabbit corneal endothelium
Authors: Fischbarg J. , Lim J. J.
Published: December 2014

1. A small electrical potential difference (541 ± 48 μV, aqueous side negative) across rabbit corneal endothelium has been recently found. Its dependence on ambient [Na+], [K+], [H+] and metabolic and specific inhibitors was examined.

2. Changes in concentration of the ions above either were known or were presently shown to affect the rate of fluid transport across this preparation (normal value: 5·2 ± 0·4 μl./hr.cm2). Ionic concentration changes were also found here to influence potential difference in the same way as fluid transport. In the cases tested, the effects on both fluid transport and potential difference were reversible.

3. Fluid transport and potential difference were both decreased or abolished in absence of Na+, K+ and HCO3−, and when [H+] was decreased. Fluid transport and potential difference were saturable functions of [HCO3−] and half‐saturation occurred in both cases at about 13 m
M‐HCO3−. The potential difference was also a saturable function of [Na+] (half‐saturation around 15 m
M). There was a pH optimum for potential difference in the range 7·4–7·6. Lower pH values decreases the potential difference and the fluid transport, and a small (−100 μV) reversed potential was observed in the range of 5·3–5·5.

4. Total replacement of Cl− by HCO3− or SO42− produced no impairment on either fluid transport or potential difference.

5. Carbonic anhydrase inhibitors (ethoxyzolamide 10−5 or 10−4
M and benzolamide 10−3
M) produced a 40–60% decrease in the rate of fluid pumping. In contrast, ethoxyzolamide 10−4
M or acetazolamide 10−3
M did not produce any change in the potential difference. NaCN and Na iodoacetate (both 2 m
M) eliminated the potential difference in 1‐1·5 hr while in controls it lasted for 5‐6 hr.

6. Ouabain (10−5
M) abolished the potential difference in less than 10 sec when added to the aqueous side, which suggests the existence of an electrogenic pump. This extremely fast time transient can be accounted for by the accessibility and simple geometry of the present monocellular layer. Ouabain abolished also the reversed potential difference observed at low pH.

7. The data are interpreted in terms of a scheme similar to that advanced for other epithelia and in which (a) H+ would be pumped into the intercellular spaces, while Na+ and CO2 would enter into the cells, and (b) Na+ would be subsequently pumped into the aqueous humour, producing as a result the fluid movement observed. The actual origin of the potential difference is further discussed in terms of two contrasting possibilities: (i) one or more electrogenic pumps, and (ii) a neutral pump which would create a diffusion potential across ‘leaky’ intercellular junctions.
The relation of oxygen intake and speed in competition cycling and comparative observations on the bicycle ergometer
Authors: Pugh L. G. C. E.
Published: December 2014

1. The relation of V̇O2 and speed was determined on six competition cyclists riding at speeds ranging from 12 km/hr to 41 km/hr on the runway of an airfield. Comparative measurements were made on the bicycle ergometer to determine the corresponding work rates, and from this information rolling resistance and air resistance were derived.

2. V̇O2 was a curvilinear function of cycling speed, and increased from 0·88 l./min at 12·5 km/hr to 5·12 l./min at 41 km/hr, mean body weight being 72·9 kg.

3. On the ergometer, V̇O2 was a linear function of work rate; maximum values up to 5·1 l./min (74·4 ml./kg min) and work rates up to 425 W (2600 kg m/min) were observed.

4. Data are presented on the relation of pedal frequency and speed in cycling, and on the relation of mechanical efficiency and pedal frequency, as determined on the ergometer.

5. The estimated rolling resistance for four subjects was 0·71 kg f. The drag coefficient was 0·79 and the drag area 0·33 m2. The values agreed well with results obtained by other methods.

6. The energy expenditure (power developed) in cycling increased approximately as the square of the speed, and not as the cube of the speed as expected. This was explained by the varying contribution of rolling resistance and air resistance to over‐all resistance to motion at different speeds.
Metabolic and ionic requirements for the axoplasmic transport of dopamine β‐hydroxylase
Authors: Garcia A. G. , Kirpekar S. M. , Prat J. C. , Wakade A. R.
Published: December 2014

1. Metabolic and ionic requirements for the intra‐axonal transport of dopamine β‐hydroxylase (DBH) were investigated in the cat hypogastric nerve‐inferior mesenteric ganglion preparation in vitro by monitoring the enzyme accumulation above a crush, 2‐2·5 cm distal to the ganglion.

2. DBH accumulation in the proximal segment immediately above the crush increased linearly up to 6 h, during incubation in normal Krebs solution at 37° C. The rate of transport of the enzyme was about 4 mm/h.

3. Removal of the ganglion, electrical stimulation or reserpine pretreatment (1–6 days before the experiment) did not modify the rate of DBH accumulation.

4. Anoxia and glucose deprivation, singly, did not affect accumulation of DBH; however, the combined treatment of anoxia plus glucose deprivation, or dinitrophenol plus glucose deprivation, very markedly interfered with accumulation.

5. Removal of sodium or potassium from Krebs solution markedly inhibited the transport of DBH. Preincubation of the nerve in a high‐calcium Krebs solution at 4° C, and then reincubation at 37° C, prevented the enzyme accumulation.

6.
N‐ethylmaleimide, ouabain and oligomycin markedly inhibited the transport of DBH.

7. The results suggest that transport of DBH, and therefore of noradrenaline storage vesicles, within the hypogastic nerve is dependent on metabolic energy derived from either glycolysis or oxidative phosphorylation. It is also suggested that the sodium‐potassium‐activated ATPase may play an important role in the intra‐axonal transport of storage vesicles.
On the role of vasopressin and angiotensin in the development of irreversible haemorrhagic shock
Authors: Errington M. L. , e Silva M. Rocha
Published: December 2014

1. Long‐lasting haemorrhagic hypotension (4·5 hr at 35 mmHg) leading to irreversible haemorrhagic shock, has been studied in normal dogs, in dogs treated with a bradykinin potentiating nonapeptide (BPP9a), which blocks the conversion of angiotensin I to angiotensin II, and in dogs with experimental chronic diabetes insipidus (DI dogs). BPP9a was given by
I.V. injection before the start of bleeding (BPP pre‐treated group), 45 min after blood pressure had reached 35 mmHg (BPP early treated group) or 2 hr after blood pressure had reached 35 mmHg (BPP late‐treated group). After retransfusion of blood all dogs were allowed to recover and observed for a further period of 3 days.

2. Untreated control dogs developed haemorrhagic shock with tachycardia, low cardiac output, low total peripheral conductance and low stroke volume. All died within 24 hr of retransfusion, with pathological lesions typical of irreversible haemorrhagic shock.

3. BPP pre‐treated dogs developed haemorrhagic shock with bradycardia (during early shock), high cardiac output, high peripheral vascular conductance and high stroke volume when compared with the untreated controls. All pre‐treated animals survived the 3 day observation period. They were then killed and on post‐mortem showed no signs of irreversible haemorrhagic shock.

4. BPP early‐treated animals behaved like controls before BPP, but like pre‐treated animals after the drug. Only one out of eight died within the 3 day observation period.

5. BPP late‐treated dogs behaved like controls before BPP. They responded to the drug with a rise in cardiac output, peripheral vascular conductance and stroke volume, and with a fall in heart rate. These responses were, however, short‐lived. Four out of these eight animals died within the 3 day observation period, with lesions of irreversible haemorrhagic shock.

6. DI dogs developed haemorrhagic shock with tachycardia (like controls), but with high cardiac output and peripheral vascular conductance (like BPP pre‐treated dogs). The stroke volume of DI dogs was intermediate between those of controls and pre‐treated groups. All six dogs survived the 3 day observation period.

7. BPP9a had no measurable effect on the course of endotoxic shock.

8. It is suggested that the normally severe vasoconstriction of the mesenteric vascular bed, which is thought to be responsible for irreversible haemorrhagic shock, is absent or attenuated in the absence of vasopressin or angiotensin. The consequences of this on the development of irreversibility are discussed.
Current spread in the smooth muscle of the rabbit aorta
Authors: Mekata F.
Published: December 2014

1. The electrical responses of the smooth muscle cells of the rabbit aorta to both extracellular and intracellular stimulation were studied using the partitioned chamber and Wheatstone bridge method.

2. No spontaneous electrical activity was recorded when the tissue was soaked in either isotonic or hypertonic Krebs solutions, and strong depolarizing currents also failed to trigger action potentials in either solution.

3. The circular muscle of the aorta has cable properties. Mean values in isotonic Krebs solution were 2·1 mm for space constant and 433 msec for time constant.

4. The input resistance (mean 12 MΩ) measured with the Wheatstone bridge method was considerably smaller than that calculated from values measured with the partitioned chamber method.

5. Electrotonic potentials could be recorded from the smooth muscle of ‘injury bundles’ although their amplitude was smaller than that from the intact bundle.

6. High concentrations of noradrenaline readily induce oscillatory potentials from the aorta in both isotonic and hypertonic Krebs solutions. It was estimated by simultaneous recording with two micro‐electrodes that noradrenaline‐induced oscillatory potential can conduct in both longitudinal and transverse directions of the smooth muscle.

7. These results suggest that the smooth muscle of the aorta behaves like a syncytium or single unit muscle and activation of cells on the inner surface of the media can be induced both by electrotonic current spread and by propagation of oscillatory potentials from the outer cells directly activated by the transmitter.
Electrophysiological evidence for the activation of supraoptic neurones during the release of oxytocin
Authors: Lincoln D. W. , Wakerley J. B.
Published: December 2014

1. Antidromically identified supraoptic (SO) units were recorded in lactating rats anaesthetized with urethane (1·1 g/kg), and their activity was studied during milk ejection evoked by the suckling of the young. Fifty‐eight SO units were recorded through 174 milk ejections. Each milk ejection was the result of a neurohypophysial release of an oxytocin pulse of 0·5–1·5 m‐u.

2. Fifty‐five of the SO units displayed background activity and three were silent. The firing rates ranged from 0 to 15·4 spikes/sec, the distribution was exponential with 26% of the units firing at < 1 spike/sec. Sixteen (28%) of the SO units displayed a phasic pattern of activity characterized by periods of activity (6–132 sec) and silence (4–71 sec).

3. Twenty‐five of the non‐phasic units displayed a large and stereotyped acceleration in spike activity some 10·5–17·4 sec before the rise in intramammary pressure at milk ejection. Units accelerated to rates between 9–66 spikes/sec, an increase of about thirtyfold (median) on background activity. The response was brief (0·9–4·7 sec) and was followed by a period of after‐inhibition.

4. It was concluded from studies of double recordings and observations of multi‐unit activity that all the responsive units were synchronously activated. The mean latency of 13·3 sec between the onset of the neurosecretory response and milk ejection was similar to that observed following the experimental release of endogenous oxytocin by electrical stimulation of the neurohypophysis (50 pulses/sec for 2‐4 sec).

5. Four of the phasically active units were correlated with the oxytocin release for milk ejection. Three of these units displayed a burst of activity superimposed on the terminal portion of an active phase, some 10·2–14·7 sec before milk ejection. The fourth unit, recorded in conjunction with a responsive non‐phasic unit, consistently switched from silence to activity coincident with the onset of the SO activation.

6. The remaining SO units and a further ten units that were not antidromically activated by neurohypophysial stimulation displayed no change in activity during either the period of neurosecretory activation or the period of after‐inhibition.

7. This activation of the SO neurones, in the formulation of oxytocin release and milk ejection, is the same as that we have previously observed in recordings from the paraventricular (PV) region, and the proportion of neurones displaying the response is similar: 48% in the SO nuclei, 58% in the PV nuclei. We conclude, since the SO nuclei contain 80% of the neurosecretory cells that project to the neurohypophysis, that the SO nuclei are as important, if not more so, than the PV nuclei in the control of oxytocin release.
The effects of caffeine on the contraction of the frog heart
Authors: Chapman R. A. , Miller D. J.
Published: December 2014

1. The force of contraction and the membrane potentials have been measured from preparations of frog heart, with methods that also allow the rapid exchange of the extracellular fluid.

2. In regularly beating preparations, caffeine induces only weak contractures at temperatures above 15° C, but it does cause a marked potentiation of the twitch responses; longer exposure results in a depression of contraction. The build up and decline of the twitch strength, on addition and on removal of caffeine approximates to a single exponential, time constant 26–45 sec, and this time constant is not altered by variation of the [Ca]o, the stimulus rate or the caffeine concentration. This time course of the change of twitch strength is less complex than the changes seen when either [Ca]o or the stimulus rate is altered, suggesting a more direct action of caffeine on excitation‐contraction coupling.

3. Caffeine increases the strength of the contractures initiated by potassium‐rich or sodium‐depleted solutions in isolated atrial trabeculae.

4. After the spontaneous relaxation of the contracture, evoked by either sodium‐free or potassium‐rich fluids, the application of caffeine initiates a redevelopment of tension. This caffeine contracture is transient and its strength is dependent on the caffeine concentration. The response in sodium‐free solution can be elicited in the virtual absence of extracellular calcium.

5. Local anaesthetics antagonize the caffeine contracture.

6. The results suggest that the sarcoplasmic reticulum of frog heart muscle plays an important role in the initiation and control of contraction and relaxation.