bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of renal denervation and meclofenamate on renal blood flow regulation in conscious rabbits
Authors: Beilin L. J. , Bhattacharya J.
Published: December 2014

1. The effect on renal blood flow regulation of unilateral renal denervation followed by administration of a prostaglandin synthesis inhibitor has been studied in nine conscious rabbits.

2. Renal blood flow distribution was estimated using radioactive microspheres injected via a pre‐implanted left ventricular cannula. Cardiac output was estimated by thermodilution. Measurements were made before and after intravenous injection of Meclofenamate, Parke Davis Ltd (4 mg/kg).

3. Renal denervation caused a fall in renal cortical catecholamine concentration of approximately 50% by 48 hr.

4. Resting renal blood flow did not differ significantly between denervated and innervated kidneys.

5. Meclofenamate caused a significant rise in arterial pressure from a mean of 59 to 70 mmHg. In innervated kidneys, Meclofenamate caused a fall in renal blood flow from 8·1 ± 0·6 (mean ±
S.E. of mean) to 6·5 ± 0·4 ml./min.g kidney weight while in denervated kidneys it caused a fall from 8·9 ± 0·7 to 6·25 ± 0·3 ml./min.g.

After Meclofenamate flow was redistributed away from the inner cortex in the innervated kidney and paradoxically towards the inner cortex in the denervated one.

6. It was concluded that in conscious animals, resting sympathetic tone has little effect on renal blood flow. The exaggerated reduction in flow in the outer cortex of the denervated kidney following Meclofenamate may indicate denervation hypersensitivity to circulating catecholamines unmasked by reduced synthesis of vasodilator prostaglandins. Alternatively, renal sympathetic nerves may normally prime prostaglandin synthesis in the outer cortex.
Intracellular pH and the distribution of weak acids and bases in isolated rat superior cervical ganglia.
Authors: Brown D A , Garthwaite J
Published: December 2014

1. The steady‐state intracellular/extracellular concentration ratios (Ci/Co) of a number of radiolabelled weak bases in isolated rat superior cervical ganglia were measured. 2. Observed values for Ci/Co (mean +/‐ S.E. of mean) were [3H]nicotine, 6.17 +/‐ 0.12; [14C]morphine, 6.08 +/‐ 0.14 [3H]atropine, 7.10 +/‐ 0.16; [14C]trimethylamine, 6.73 +/‐ 0.13; [14C]procaine, 10.13 +/‐ 0.26. If Ci/Co were determined by the transmembrane pH gradient, the intracellular pH (pHi) appropriate to these concentration gradients lay between 6.4 and 6.6 at an extracellular pH (pHo) of 7.4. 3. the steady‐state value of Ci/Co for the weak acid 5,5‐dimethyl‐2,4‐oxazolidinedione (DMO) was 0.87 +/‐ 0.007. The appropriate pHi was 7.31 +/‐ 0.003. 4. The difference between the values of pHi calculated from the distribution of the weak bases and of DMO could not be attributed to (i) experimental error, (ii) partial permeation of protonated base, (iii) intracellular binding or carrier‐mediated transport of base, (iv) lipid uptake of base or (v) different pK'a inside and outside cells. 5. The difference between the measurements of pHi made with DMO and nicotine (pHDMO‐pHnic) was reduced or abolished by uncoupling agents, which act as transmembrane proton carriers. This effect was not reproduced by respiratory inhibitors or by exposure to lactate. 6. pHDMO‐pHnic was small (less than 0.1 units) in human erythrocytes, which contain no intracellular organelles, and was exaggerated (1.0 unit) in slices of lipid‐depleted brown adipose tissue which contained an abundance of mitochondria. 7. It is concluded that the different values of pHi determined using weak acids and bases arise from the presence of membrane‐bound intracellular compartments of differing pH, and that where the use of pH‐sensitive micro‐electrodes is impracticable, it is desirable to measure pHi with both a weak acid and a weak base unless these can be shown equal over a wide range of pHi values.
Sodium‐sodium exchange through the sodium pump: the roles of ATP and ADP.
Authors: Cavieres J D , Glynn I M
Published: December 2014

1. We have developed a procedure for preparing resealed red cell ghosts that contain ADP but very little ATP. 2. The procedure involves (i) lysis of the cells in a very large volume of lysing solution, (ii) resuspension of the ghosts in a small volume, (iii) the incorporation into the ghosts, before they are resealed, of the adenylate kinase inhibitor P1,P5‐di(adenosine‐5'‐)pentaphosphate (AP5A) and of hexokinase, and (iv) the removal of traces of ATP, formed by residual adenylate kinase activity, by the addition of glucose. 3. Measurements of sodium efflux from ghosts prepared in this way show that sodium‐sodium exchange through the sodium pump does not occur in the absence of ATP even if ADP is present. 4. The beta:gamma imido analogue of ATP (AMP.PNP), which is incapable of phosphorylating sodium, potassium‐ATPase, cannot replace ATP in supporting sodium‐sodium exchange. 5. These findings support the hypothesis that the outward movement of sodium ions through the sodium pump is associated with the transfer of a phosphoryl group from ATP to the enzyme, and that the inward movement of sodium ions through the pump is associated with the return of a phosphoryl group from the phosphoenzyme to ADP.
Changes in partial pressure of carbon dioxide with time in carotid arterial blood in cats.
Authors: Carruthers B , Ponte J , Purves M J
Published: December 2014

1. A rapidly responding CO2 sensor and cuvette were placed in the carotid artery of anaesthetized cats and changes of PCO2 in post‐pulmonary capillary blood were recorded when flow through the cuvette was suddenly stopped. 2. Under control conditions when the cats breathed spontaneously or were ventilated artificially, stop‐flow caused Pa, CO2 to decay by 2‐‐5 mmHg reaching a new equilibrium in 10‐‐15 sec. The amount by which CO2 decayed was reduced by the inhalation of high O2. The decay was enhanced by hypoxia, the inhalation or infusion of CO2. It was reversed by the administration of acetazolamide: now with stop‐flow, Pa, CO2 rose by 8‐‐15 mmHg. 3. the mechanism of this decay is uncertain. We propose that it is due to the transfer of CO2 from plasma to red cells in post‐capillary blood in response to the reduction of [H+]i as H+ binds to Hb following the oxylabile release of CO2 from Hb.
The reflex release of adrenaline and noradrenaline from the adrenal glands of cats and dogs.
Authors: Critchley J A , Ellis P , Ungar A
Published: December 2014

1. We have studied the release of noradrenaline and adrenaline from the adrenal glands of dogs and cats in response to the lowering of carotid sinus pressure (baroreceptor tests) and to the perfusion of the vascularly isolated carotid bifurcations with hypoxic blood (chemoreceptor tests). 2. In cats, the resting output of catecholamines had a ratio of noradrenaline to adrenaline of 1:1. The ratio in the incremental release during baroreceptor tests rose to 3:1, and during chemoreceptor tests it fell to 1:6. 3. In dogs, the ratio of noradrenaline to adrenaline at rest was 1:4. The ratio did not change over a wide range of outputs during baroreceptor tests, chemoreceptor tests and splanchnic nerve stimulation. 4. The release of catecholamines in response to baroreceptor tests in the cat was abolished by hexamethomium bromide at doses that did not diminish the response to chemoreceptor tests.
Electrophysiological properties of the smooth muscle cell membrane of the dog coronary artery.
Authors: Mekata F
Published: December 2014

1. The electrical properties of dog coronary arterial smooth muscles were studied with the partitioned chamber method and Wheatstone Bridge method. Effects of intracellular and extracellular current and of field stimulation of nerve were examined. 2. Muscle from the anterior descending coronary artery showed cable properties, with a 2.4 mm space constant and a 455 msec time constant. Muscle strips from the circumflex coronary artery showed poor cell‐to‐cell connexions. 3. The smooth muscle of both coronary arteries was electrically quiescent and action potentials were not evoked even by strong outward current. 4. Field stimulation of the descending coronary artery induced either contraction or relaxation which were respectively associated with depolarization and hyperpolarization. These responses were blocked by tetrodotoxin (2 x 10(‐7) g/ml). 5. Field stimulation produced depolarization when the membrane potential was higher than 60 mV and hyperpolarization when the membrane potential was lower than ‐50 mV. 6. The results suggest that, in the descending coronary artery, the smooth muscle including the innermost cells can be controlled by nerve.
The effect of diet on tissue levels of kinin‐forming enzyme in blood‐free rat gastro‐intestinal tract
Authors: Frankish N. H. , Zeitlin I. J.
Published: December 2014

1. Kallikreins, kinin‐forming enzymes, are present in the wall of the gastro‐intestinal tract. The role of the kinin‐forming system in the gut is unknown. In the present study, a modified bio‐assay technique was used to detect the presence of tissue concentration gradients of kinin‐forming enzyme (KFE) at different levels of the rat gastro‐intestinal tract and the effect on them of diet.

2. Segments of rat gut, perfused free of blood, were homogenized in 0·1
N‐HCl and activated by autolytic processes. Total KFE content was then determined by incubation of extract with standard kinin‐forming substrate, followed by bio‐assay of the released kinin using superfused oestrous rat uterus. Acid extraction of the KFE gave a recovery of 127·4% when compared with simple water extraction.

3. Tissue concentrations of KFE were determined in stomach, duodenum, jejunum, terminal ileum, caecum and proximal and distal colon. Concentrations were determined after (A) normal diet, (B) water ad libitum for 24 hr and (C) isotonic glucose ad libitum for 60 hr.

4. All the gut tissues contained KFE. After diet A there was least (19·5 ± 1·0 ng bradykinin equivalent formed per minute (KU) per gram wet weight) in the stomach and a single large peak (504 ± 92 KU .g−1 wet weight) in the caecum.

5. The different dietary states produced changes only in the duodenum, the caecum and the distal colon. The duodenal level was raised when the organ was empty after diet B (140 ± 29 KU .g−1) and fell when filled with solid or fluid after diets A (57 ± 14 KU .g−1) and C (80 ± 17 KU .g−1) respectively. The caecal KFE level, which was high when the lumen was full after diet A, fell progressively as it was increasingly emptied after diets B (213 ± 41 KU .g−1) and C (105 ± 42 KU .g−1) respectively. The KFE concentration in the distal colon was low when the lumen was full after diets A (58 ± 10 KU .g−1) and B (66 ± 17 KU .g−1) and rose when the lumen was nearly empty after diet C (118 ± 17 KU .g−1).

6. Kinin‐forming activity in rat intestinal extracts had a pH optimum at pH 8·5 and formed a bradykinin‐like spasmogen. The increased activity in the fasted rat duodenum was not significantly inhibited by soybean trypsin inhibitor (100 μg/ml.) while that in caeci from fed rats was inhibited by 17% (P < 0·05).

7. These changes may indicate physiological involvement of the kallikrein‐kinin system in these organs.
Feeding in sheep during intraportal infusions of short‐chain fatty acids and the effect of liver denervation
Authors: Anil M. H. , Forbes J. M.
Published: December 2014

1. Castrated male sheep were prepared with cannulae in the hepatic portal vein and jugular vein through which infusions lasting for 3 hr were made. Animals had free access to a pelleted feed the weight of which was continuously recorded so that feeding behaviour could be studied.

2. Infusion into the portal vein of a mixture of salts of short‐chain fatty acids (acetate, propionate, butyrate: 55, 30, 15) caused a dose‐dependent depression in food intake, feeding stopping completely with 4·0 m‐mole/min of the mixture. Jugular infusion depressed intake slightly, compared with controls.

3. Separate infusions of salts of the three acids showed that the effect of the mixture was due almost entirely to its propionate content; 1·2 m‐mole/min of propionate into the portal vein almost completely prevented feeding (39 g eaten per 3 hr) compared with jugular infusion at the same rate (210 g) or no infusion (205 g).

4. Surgical sectioning of the hepatic nerve plexus around the wall of the hepatic artery was attempted. Of seven animals which recovered normal food intake, three continued to eat during portal vein infusions of propionate at 1·2 m‐mole/min; these sheep were subsequently shown to have been at least 95% denervated. One animal was 50% denervated and ate normally during some infusions but not others. In the remaining three, feeding was suppressed by portal vein infusion of propionate, and these were less than 75% denervated.

5. It was concluded that there are receptors in the liver which are sensitive to propionate and which have afferent fibres in the hepatic plexus.
Vagal afferent discharge from mechanoreceptors in different regions of the ferret stomach.
Authors: Andrews P L , Grundy D , Scratcherd T
Published: December 2014

1. The rate and volume of gastric filling was estimated in conscious ferrets by measuring the amount of milk they would drink after an overnight fast. The mean volume was 94.5 +/‐ 7.5 ml. at a rate of 13.0 +/‐ 0.74 ml./min. An intragastric infusion rate of 10 ml./min to a total of 50 ml. was selected as a standard distension stimulus. 2. Action potentials were recorded from single gastric afferent fibres in the cervical vagus. All but two of thirty‐six afferent units were tonically active when the stomach was deflated. 3. Afferent fibres arising from receptors in the antrum showed modulation in phase with spontaneously occurring antral contractions. Afferent fibres from the corpus and fundus, however, discharged at irregular rates between 0.35 and 7.5 Hz with no correlation with the intragastric pressure rises associated with the antral contractions. 4. Inflation of the stomach with 50 ml. 0.9% NaCl at a rate of 10 ml./min stimulated antral motility and the rhythmic afferent discharge from the antrum was enhanced Receptors in the corpus and fundus increased their rate of discharge with increasing gastric volumes. Receptors in the region between the antrum and the corpus had the property of both types so that they responded to both distension and contractions. 5. On distension with 0.9% NaCl, fluid is distributed unevenly in the stomach. 80% was accommodated in the corpus and fundus, the remainder of the fluid entering the antrum. 6. The tension was measured in strips of stomach wall taken from corpus and antrum. For equal increments of stretch the development of tension was greater in the antral than in corpus strips. This physical property together with neurally mediated receptive relaxation of the corpus is the reason for the fluid distribution described above. 7. It is concluded that the properties of the tension receptor are determined by their site in the stomach. Those in the body and fundus signal the degree of distension and those in the antrum signal information concerning the amplitude, rate and duration of antral contractions.
Post‐synaptic conductance increase associated with presynaptic inhibition in cat lumbar motoneurones.
Authors: Carlen P L , Werman R , Yaari Y
Published: December 2014

1. Motoneurones were examined in which low‐intensity p.b.s.t conditioning volleys caused a 5% or greater decrease of gastrocnemius monosynaptic e.p.s.p.s without evidence of long‐lasting i.p.s.p.s on superimposed single sweeps. 2. Short constant current pulses were injected into these cells and in twenty‐two of twenty‐three cases the voltage decay was faster when preceded by the same p.b.s.t. conditioning stimuli which caused a decrease in the Ia e.p.s.p. 3. Comparing these decays to short pulse decays generated in a simple analogue neurone model suggested that after conditioning stimuli a tonic conductance increase had occurred which was located electrotonically remote from the soma in some cases or more diffusely in other cases. 4. Long‐lasting i.p.s.p.s were brought out by averaging the baseline following conditioning stimuli in ten of fifteen cases, also suggesting a post‐synaptic conductance increase. 5. Averaging the voltage response to long saturating constant current pulses showed a decreased motoneurone input resistance in three of eight cases. 6. The semilogarithmic decay of four of eleven conditioned e.p.s.p.s was more rapid than controls. 7. Although short pulse voltage decay analysis revealed consistent evidence for increased post‐synaptic conductance following conditioning stimuli, it was not possible to decide if the location and extent of this conductance increase were sufficient to rule out presynaptic inhibition.
The measurement of colonic mucosal‐submucosal blood flow in man.
Authors: Forrester D W , Spence V A , Walker W F
Published: December 2014

1. A method is described for the measurement of colonic mucosal‐submucosal blood flow in man, by studying surgically created colostomies. 2. A local radioisotopic clearance technique utilizing a stable preparation of [125I]4‐iodoantipyrine is employed. The indicator is injected directly into the colostomy under study and its gamma emission is recorded by a scintillation detector. 3. A radioautographic study was carried out at laparotomy in humans to facilitate the interpretation of the recorded washout curves. This demonstrated that the tracer was cleared from both the mucosa and submucosa throughout the period of study. 4. Mucosal‐submucosal blood flow was calculated according to Kety (1949) from the monoexponential clearance curves obtained, and amounted to 31.7 +/‐ 11 ml./min. 100 g (S.D. of an observation, n = 30). 5. The results from two consecutive measurements in seventeen patients showed that the mean change between first and second readings was not significant (t test). In addition the between‐patient variation (12.2) was significantly greater than the within‐patient variation (2.6) for consecutive recordings (F test; P less than 0.01). 6. The within‐patient between‐days variation (12.9; n = 10) was found to be similar to the between‐patient variation. 7. It is concluded that the technique permits measurement of local colonic blood flow in man and by consecutive measurements, it may be used to evaluate local changes in blood flow following reflex or pharmacological stimulation.
Presence of renotrophic factor in plasma of unilaterally nephrectomized rats.
Authors: Dicker S E , Morris C A
Published: December 2014

1. Renal cortical slices cut in two halves were incubated separately in culture medium. One half slice was used as control while the other half was treated experimentally. After incubation, their dry weights and/or their protein content were estimated. 2. Addition to half cortical slices of 30 micrograms mg‐1 of freeze‐dried plasma from rats killed 24 hr after unilateral nephrectomy resulted in an increase of dry weight or protein content of the order of some 10% after 4‐8 hr incubation. 3. The effect of freeze‐dried plasma from rats killed 24 hr after unilateral nephrectomy was specific to the renal cortex. When added to half slices from either the renal medulla or the liver there were no changes in their dry weight. 4. Addition of 30 micrograms mg‐1 of freeze‐dried plasma from rats killed 24 hr after bilateral nephrectomy had no significant effect on the dry weight of half cortical slices incubated for various periods of time, from 4 to 48 hr. 5. The renotrophic activity of plasma from unilaterally nephrectomized rats, killed 24 hr after the operation, appears to be metabolized or destroyed by incubation with cortical slices in 4 hr. 6. Freeze‐dried plasma from normal unilaterally nephrectomized rats produced an increase dry weight when incubated for 4 hr with half cortical slices from early (3 days) hypophysectomized rats. When incubated with half cortical slices from late (23 days) hypophysectomized rats, the increase in dry weight was about 2 times as great as that observed with cortical slices from normal animals. 7. The possible reason for the production of renotrophic activity in plasma of unilaterally nephrectomized rats, and for its absence in plasma of anephric animals, is discussed.
The effect of carbonic anhydrase inhibitors on the anionic composition of sheep's parotid saliva. With an appendix on uncatalysed carbon dioxide‐water kinetics by P. T. McTigue.
Authors: Blair‐West J R , Fernley R T , Nelson J F , Wintour E M , Wright R D
Published: December 2014

1. The effects of the carbonic anhydrase inhibitors, acetazolamide, ethoxzolamide and benzolamide on the ionic composition of parotid saliva were studied in anaesthetized sheep with access to the parotid blood vessels. 2. The inhibitors were infused directly into the arterial blood supply to the gland to give blood concentrations in the range 10(‐5) to 10(‐2) M. 3. Mean anionic concentrations at basal flow rate before inhibitor infusion were, bicarbonate 98 m‐mole/l., phosphate 15 m‐mole/l. and chloride 26 m‐mole/l. In the presence of inhibitors, bicarbonate concentration fell by 11 m‐mole/ml. and phosphate and chloride concentrations rose. Secreto‐motor nerve stimulation increased bicarbonate concentration by 13 m‐mole/l. before infusion of inhibitors and the concentrations of the other anions fell. The bicarbonate rise was abolished by the inhibitors and the fall in phosphate concentration was balanced by a rise in chloride concentration. 4. These effects show that only a small component of the bicarbonate ion transfer system in the sheep parotid gland is sensitive to these inhibitors. 5. The relationship of these findings to a new enzyme with carbonic anhydrase action isolated from the sheep's parotid gland is discussed.
Haemodynamic responses to stimulation of the cardiac autonomic nerves in the anaesthetized cat with closed chest
Authors: Barnes R. J. , Bower E. A. , Rink T. J.
Published: December 2014

1. The changes in cardiac output and mean right atrial pressure (R.A.P.) evoked by stimulation of the cardiac autonomic nerves were investigated in cats under chloralose anaesthesia, with unopened chests and spontaneous respiration, and with active vascular reflexes. Cardiac output was measured by thermal dilution; the technique used was calibrated against the direct Fick method.

2. The initial values of R.A.P. and output were varied by infusion of dextran‐saline solution followed by withdrawal of blood. At positive values of R.A.P. withdrawal of blood caused a fall in R.A.P. with no change in cardiac output. At negative R.A.P. blood withdrawal caused a fall in output with little change in R.A.P.: the linear regression coefficient for output on R.A.P. was 48·2 ml./min.kg.mmHg (
S.E. 2·06, n = 63, nine cats).

3. Stimulation of the right cardiac sympathetic nerve increased heart rate by 69·2 beats/min (
S.E. 4·0) from the resting rate of 158 beats/min (
S.E. 6·3, ten cats). The acceleration was accompanied in most instances by a rise in cardiac output and a fall in R.A.P. and the magnitude of the rise in output was related to that of the fall in R.A.P.

4. In no experiment could R.A.P. be reduced below ‐2·5 mmHg either by withdrawal of blood or by sympathetic stimulation. At negative values of R.A.P. the fall in R.A.P. and rise in output evoked by sympathetic stimulation were small; substantial changes could be obtained only from positive initial values of R.A.P. The proportional increase in output evoked by a given proportional increase in heart rate during near‐maximal sympathetic stimulation had a linear relationship to the initial value of R.A.P. over the range ‐2 to +8 mmHg. The output increment was less than proportional to the rate increment at all values of R.A.P. below +3 mmHg.

5. In five experiments stimulation of the left cardiac sympathetic nerve evoked a greater increase in output for a given increase in heart rate than did stimulation of the right nerve; on the other hand both nerves gave similar increments of output for a given fall in R.A.P.

6. Stimulation of the distal end of the right vagus nerve slowed the heart and caused a fall in cardiac output and a rise in R.A.P. The change in output associated with a given change in R.A.P. was significantly greater (P = 0·05) during sympathetic than during vagal stimulation in 14 out of 18 tests; the difference increased as circulating volume was reduced.

7. It is concluded that the relationship between cardiac output and R.A.P. during sympathetic and vagal stimulation is consistent with the hypothesis that neurally evoked changes in cardiac performance vary output mainly, but not exclusively, by inducing changes in R.A.P. which alter the pressure gradient for the return of blood to the right atrium from the periphery.
A comparison of effects evoked in guinea‐pig taenia caecum by purine nucleotides and by ‘purinergic’ nerve stimulation
Authors: Jager L. P. , Schevers J. A. M.
Published: December 2014

1. Effects of adenosine and the adenosine nucleotides (ATP, ADP, AMP and CoA) on the guinea‐pig taenia caecum were studied by measuring simultaneously the changes in membrane potential and in contractility induced by these agents using the sucrose‐gap technique.

2. In the presence of carbachol (5 × 10−8
M) the hyperpolarization and the relaxation induced by these agents was found to be closely correlated. Their different potencies suggested an action on the P2 type purinoceptor: ATP ≥ ADP ≥ AMP > CoA > AD.

3. The transmitter released endogenously in the presence of carbachol (5 × 10−8
M) by the non‐adrenergic inhibitory (n.a.i.) nerves after half‐maximal stimulation induced an inhibitory junction potential (i.j.p.) which transiently counteracted the carbachol‐induced depolarization. This i.j.p. was mimicked by ATP, ADP, and AMP applied exogenously in concentrations of about 3 × 10−5
M, by CoA (3 × 10−4
M) and by adenosine (3 × 10−3
M).

4. The results presented are in agreement with the hypothesis that the transmitter substance released by the n.a.i. nerves is a purine nucleotide, which in the guinea‐pig taenia caecum affects the smooth muscle cell membrane via the P2‐purinoceptor. Of the putative transmitters studied, ATP, ADP and AMP seem the most likely.
Renin release from isolated rat glomeruli: effects of colchicine, vinca alkaloids, dimethylsulphoxide, and cytochalasins.
Authors: Baumbach L
Published: December 2014

1. Preparations of isolated glomeruli were superfused and the effects of colchicine, the vinca alkaloids, and the cytochalasins A, B, D, and E investigated on basal renin release and the response of the glomeruli to osmotic stress. 2. Colchicine (10(‐3) M) had no effect, whereas vinblastine and vincristine (10(‐5) M) caused a progressive increase in basal renin release from isolated glomeruli. 3. After 60 min exposure to either colchicine or the vinca alkaloids, the first renin release response to a hypoosmotic challenge (reduction in sucrose or sodium chloride concentration) was depressed while that of the second (after 120 min exposure) was enhanced. 4. Addition of 0.5% dimethylsulphoxide (DMSO) and each of the cytochalasins A, B, D, and E (5 micrograms/ml.) had no significant effect on basal renin release. 5. DMSO (0.5%) depressed the release response to the first 20 m‐osmole/kg reduction in medium osmolality obtained by lowering the sucrose concentration. This effect had vanished at the time of the second 20 m‐osmole stimulus (120 min). 6. The normal response to the first 30 m‐osmole/kg reduction in NaCl concentration (and medium osmolality) was abolished by 0.5% DMSO. Rather, a depressed release compared to unstimulated control experiments was observed. The response to the second stimulus in the presence of DMSO was about half that of control experiments. 7. Following the first hypoosmotic stimulus (by lowering the concentrations of sucrose of NaCl) the cytochalasins A, B, D and E (5 micrograms/ml.) caused an increased release of renin which persisted throughout the length of the experiment. The cytochalasins used were equally potent in this respect. 8. The results are in agreement with previous findings, suggesting that renin release from the juxtaglomerular cells adhering to isolated glomeruli is mediated through a mechanism different from exocytosis.
Importance of the kidneys for gastrin elimination and gastric function
Authors: El Munshid H. A. , Håkanson R. , Liedberg G. , Rehfeld J. F. , Sundler F.
Published: December 2014

1. The gastrin concentrations in serum were elevated after nephrectomy in rats and mice indicating the importance of the kidney for elimination of gastrin in these species. In guinea‐pigs and rabbits nephrectomy did not cause increased serum gastrin concentrations. In rats there was a gradual rise in the serum gastrin level up to 48 hr after bilateral nephrectomy and also after ureteral ligation. After the latter operation the concentrations of gastrin in serum were lower than after nephrectomy. Significant elevation of the gastrin level 48 hr after ureteral ligation indicates that gastrin is eliminated at least partly through glomerular filtration. The gastric histidine decarboxylase activity after nephrectomy or ureteral ligation generally reflected the concentration of circulating gastrin.

2. After bilateral ureteral ligation gastric acid secretion in conscious fistula rats was uniformly inhibited with no response to pentagastrin or histamine 24 or 48 hr after the operation. After nephrectomy basal acid secretion was reduced and there was no response to pentagastrin. The response to histamine was still present, although reduced at all dose levels. Linear transformation of the dose—response curve indicated mixed inhibition. The incidence of gastric ulcer was 75% 48 hr after nephrectomy and 30% after ureteral ligation. Since basal and pentagastrin‐stimulated acid secretion were unaffected by nephrectomy in rats with the upper two‐thirds of the intestine removed, the intestine appears to produce factors which are responsible for the inhibition of gastric secretion.

2. On the whole, the gastrin concentration in serum and gastric histidine decarboxylase activity were not increased after five‐sixths nephrectomy. Gastric ulcers were seen in the rats with the highest serum urea levels; one in addition had high serum gastrin concentration and gastric histidine decarboxylase activity. Basal, pentagastrin‐ and histamine‐stimulated acid secretion were not affected by subtotal nephrectomy. It appears that in the rat about one sixth of the renal mass is the minimum required for handling gastrin degradation and excretion.
Chemical responses of polymodal receptors of the scrotal contents in dogs.
Authors: Kumazawa T , Mizumura K
Published: December 2014

1. Chemical responses of polymodal receptors of the superior spermatic nerve were studied by single unit recording in dogs. The responses were similar to those found in the muscular polymodal receptors of dogs. 2. Solutions of hypertonic NaCl, KCl and bradykinin caused responses in more than 90% of these polymodal units. The responses were related to the dose of these three chemical but discharge patterns differed substantially. Responses to Na citrate were very capricious, and those to acetylcholine and histamine were weak. 3. When bradykinin was applied repeatedly the responses of the subsequent trials decreased if the repetition interval was short (less than 15 min), but an increase of response was observed if the repetition interval was long (30‐60 min). 4. Indomethacin 10 micrograms.ml‐1 suppressed or abolished the response to 1 microgram.ml‐1 bradykinin without significant influence on the response to 60 mmol.l‐1 KCl at the same receptive site. Involvement of prostaglandins in the response of the polymodal units to bradykinin is suggested.
Force staircase kinetics in mammalian cardiac muscle: modulation by muscle length
Authors: Lakatta E. G. , Spurgeon H. A.
Published: December 2014

1. Quiescent cat papillary muscles were stimulated to contract regularly at Lmax, the length at which force production is optimal, and at 0·85 Lmax. The resulting increase in force production (rate staircase) at each length was characterized as an exponential function.

2. When stimulated from quiescence at 24 min−1 in a bathing fluid [Ca2+] of 2·5 m
M, sixteen of twenty‐three muscles exhibited biexponential increases in force production at both lengths. The coefficients of the exponential function at Lmax were 1·5‐2 times greater than their counterparts at the shorter length, and this length difference was highly significant. When the force staircases were normalized to the peak developed force attained at each length, the number of beats to attain 25, 50, 75, and 98% of peak force at 0·85 Lmax was approximately twice that required at Lmax.

3. At a given length the force staircase (1) exhibited a dependency on the number of beats rather than on stimulation frequency over a range of 12‐60 min−1, (2) was accelerated by increasing the bathing fluid [Ca2+] from 1·0 to 5·0 m
M, (3) was accelerated in the presence of isoproterenol, and (4) was retarded in the presence of
DL‐verapamil. Over the entire range of bathing fluid [Ca2+] and at all stimulation frequencies 24 min−1 and above, more beats were required to complete a given level of the normalized staircase at 0·85 Lmax than at Lmax. There was no length difference in the presence of verapamil. These data suggest that transsarcolemmal Ca2+ influx is an important determinant of the kinetics of the force staircase, and the length dependence of the latter indicates that muscle length is an important determinant of transsarcolemmal Ca2+ influx.

4. This conclusion was strengthened by the results of additional studies in which the [Ca2+] of the bathing fluid was abruptly increased from 1·0 to 5·0 m
M with the muscle beating in the steady state. The resulting increase in force production (Ca2+ staircase) was described by a monoexponential function with a greater coefficient at Lmax than 0·85 Lmax; when normalized to the peak force difference in the two [Ca2+] at each length, a given level of the staircase was achieved in significantly fewer beats at Lmax than at the shorter length.

5. The data provide a mechanism which, in part, explains the length dependence of excitation‐contraction coupling in cardiac muscle with intact sarcolemmae.
Gastric secretion provoked by functional cytoglucopoenia in the nuclei of the solitary tract in the cat.
Authors: Kadekaro M , Timo‐Iaria C , Vicentini M de L
Published: December 2014

1. A rhomboencephalic reflex loop involved in the gastrosecretory effect of functional cytoglucopoenia caused by 2‐deoxy‐D‐glucose (2‐DG) was investigated in thirty‐five cats prepared with chronic gastric fistulae. 2. Injection of 60 mg 2‐DG/kg in the vertebral artery of cats subjected to acute electrolytic transection of the pontomedullary transition produced gastric secretion. 3. Microinjection of 2‐DG in the medial and in the lateral components of the nuclei of the solitary tract elicited an intense gastric secretion. Sites at the level of the obex were more effective than the caudalmost portions of the nuclei in causing the secretory effect. Microinjection of saline in the same nuclei was totally ineffective whereas both saline and 2‐DG solutions induced secretion when microinjected in the dorsal nuclei of the vagus. The gastrosecretory effect of microinjection of saline and 2‐DG in the dorsal nuclei of the vagus is ascribed to mechanical stimulation of the effector parasympathetic neurones that innervate gastric mucosa. 4. It is concluded that rhomboencephalic neurones sensitive to functional cytoglucopoenia are located in the nuclei of the solitary tract. Activation of these neurones conveys to effector neurones information that triggers gastric secretion.
Binding of scorpion toxin to sodium channels in vitro and its modification by β‐bungarotoxin
Authors: Okamoto Harumasa
Published: December 2014

1. Binding of a purified scorpion toxin to membrane fragments isolated from electroplaque of an electric eel Electrophorus electricus was studied using a radio‐iodinated toxin.

2. A scorpion toxin was purified from the venom of Leiurus quinquestriatus and iodinated with 125I in a lactoperoxidase‐catalysed reaction. Monoiodinated toxin, isolated by an ion exchange chromatography, retarded the inactivation kinetics of Na current to a similar extent as the native toxin, indicating that radioiodination did not appreciably affect physiological and binding properties of the native toxin.

3. Analyses of binding properties by Scatchard plots showed the presence of two classes of binding sites (with low and high affinities) in the membrane preparation from eel electroplaque; similar preparation from an electric skate, of which the electroplaque is known to be devoid of Na channels, possessed only the low affinity sites.

4. The number of high affinity sites in the eel preparation was 41·8 ± 10·5 p‐mole/g tissue; the value was within the range reported for tetrodotoxin binding to similar preparations (15‐148 p‐mole/g tissue).

5. A variety of cations (Na+, Mn2+ and La3+) inhibited the high affinity scorpion toxin binding, as indicated for the toxin binding to Na channels by a previous electrophysiological study. KD value in the presence of 120 m
M‐Na+ (approx. 8 n
M) agreed reasonably with that (approx. 10n
M) reported for the scorpion toxin binding to excitable neuroblastoma cells or synaptic nerve ending particles under conditions where membrane potential was depolarized by the addition of 135 m
M‐KCl.

6. Pretreatment of the eel membrane preparation with β‐bungarotoxin (7‐44 ng/ml.) in the presence of Ca ions (10‐200 μ
M) resulted in a substantial loss of high affinity binding of scorpion toxin. When phospholipase A2 activity of the β‐toxin was inactivated by a chemical modification with p‐bromophenacyl bromide, the inhibitory action of the β‐bungarotoxin was abolished.

7. It is concluded that a high affinity binding of scorpion toxin to the eel electroplaque membrane fragments represents the binding to Na channels in vitro, and that phospholipase A2 activity of β‐bungarotoxin interferes with the binding of scorpion toxin to Na channels.
Reflex effects following selective stimulation of J receptors in the cat.
Authors: Anand A , Paintal A S
Published: December 2014

1. Experiments carried out on anaesthetized cats showed that increasing blood flow, through the lobes of a lung, by 133% (S.E. 33%) generated an average of 0.75 impulses/sec (S.E. 0.3) in ten almost silent J receptors. Equivalent activity was produced by injecting 12‐18 micrograms phenyl diguanide/kg into the right atrium. Such activity caused marked reflex effects, i.e. apnoea, rapid shallow breathing and reduction in the knee jerk. 2. The reflex effects of J receptors were studied after blocking the activity from cardiac receptors by intrapericardial injections of xylocaine. This was necessary because left atrial injections of phenyl diguanide produced reflex respiratory effects and inhibition of the knee jerk. 3. Hypoxia, but not hypercapnia, attenuated the reflex effects of J receptors, apnoea being abolished if the Pa,O2 fell below 35 mmHg. This was a central effect as it occurred in spite of increased activity of J receptors following phenyl diguanide, and effects of hypoxia persisted after cutting both carotid nerves. 4. The only invariable reflex effect of J receptors was a reduction in the total number and the average frequency of phrenic impulses in each breath. The changes in inspiratory time (ti) and expiratory time (te) following apnoea were variable although most frequently both were reduced. In about half the observations the first effect before the apnoea was a reduction in ti, in the other half it was a reduction in te. It was concluded that an input from J receptors inhibits inspiratory and expiratory mechanisms directly. 5. In some cats apnoea and rapid shallow breathing produced by J receptors continued after interrupting their activity by vagotomy and this did not diminish the reduction in ti or te; in other cats it did. The reduction in te was at times quite independent of changes in ti, i.e. pulmonary stretch receptor activity. 6. It was concluded that J receptors must be stimulated during moderate exercise to levels that produce marked respiratory reflex effects and inhibition of muscles.
Saxitoxin binding to sodium channels of rat skeletal muscles.
Authors: Bay C M , Strichartz G R
Published: December 2014

1. The saturable binding of exchange‐labelled tritiated saxitoxin (STX) to the extensor digitorum longus (e.d.l.), diaphragm and soleus muscles of adult rats was studied. By measuring STX uptake to small pieces of muscle, the dissociation constant (KD) and binding capacity could be determined for individual muscles. 2. The affinity for STX is very similar in all three muscles, with a KD of 4.3 +/‐ 0.3, 5.1 +/‐ 0.5 and 4.9 +/‐ 0.5 nM (mean +/‐ S.E. of mean) at 4 degrees C for e.d.l., diaphragm and soleus respectively. The maximum binding capacity, which varies between different muscles, is 52.6 +/‐ 2.5, 40.3 +/‐ 4.9 and 23.8 +/‐ 1.1 f‐mole.mg wet wt.‐1 respectively. 3. The affinity of e.d.l. for tetrodotoxin (TTX), measured by inhibition of STX binding, is 12.1 +/‐ 1.4 nM at 4 degrees C. Raising the temperature to 37 degrees C increases the KD for STX to 6.8 +/‐ 0.8 nM and the KD for TTX to 47.5 +/‐ 4.5 nM. 4. STX binding is pH dependent; protons compete with STX for the binding site as if there were a titratable acidic group with a pK of 5.5. 5. The binding capacity of the diaphragm is not uniform along the length of the muscle fibres. Binding at the ends of the fibres is only 78% of that in the central region. 6. Denervation of e.d.l. for 7 days causes no change in the affinity for STX. There is a slight reduction in the binding capacity from 54 +/‐ 5 to 43 +/‐ 3 f‐mole.mg wet wt.‐1. There is no change in the diameter of the muscle fibres.
The single‐photon signal in rod bipolar cells of the dogfish retina.
Authors: Ashmore J F , Falk G
Published: December 2014

1. Responses of depolarizing bipolar cells to dim light flashes were recorded with intracellular micro‐electrodes in the dark‐adapted retina of the dogfish, Scyliorhinus canicula. 2. Fluctuations in the responses were analysed by a method of matched filtering in order to improve the signal‐to‐noise ratio. 3. Both the mean and variance of the response amplitude increased linearly with light intensity for intensities not exceeding a mean of 1 photon absorbed per 50 rods. 4. On the assumption that the most significant source of the fluctuation is the quantal absorption of light by the rod outer segments, a single photoisomerization leads to a post‐synaptic event of mean size 250 micronV. 5. The mean number of rods in the pool sending signals to a bipolar cell is estimated as 1600. Individual rod pools are 90‐330 micrometer in diameter on the retinal surface. 6. It is estimated that the conductance of 1 divided by 400 of the total number of light‐modulated ionic channels in the bipolar cell is increased by a single photon acting within its rod pool. 7. In the absence of a light stimulus, the residual noise in the output of a matched filter can be interpreted as due mainly to spontaneous isomerization of rhodopsin in the rods and behaves as the ‘dark light’ postulated to limit detection at absolute threshold.
Temporal and spatial characteristics of the voltage response of rods in the retina of the snapping turtle
Authors: Detwiler P. B. , Hodgkin A. L. , McNaughton P. A.
Published: December 2014

1. In response to strong, large‐field flashes the dark‐adapted rods of Chelydra serpentina gave initial hyperpolarizing responses of 30‐40 mV, declining rapidly to plateaus of 10‐15 mV which lasted 20 sec or more.

2. In the most sensitive cells the flash‐sensitivity at 520 nm to a large illuminated area was 3‐6 mV per photoisomerization (assuming an effective collecting area of 13·6 μm2).

3. The initial response to a step of light agreed with that predicted by super‐position from the flash response but even with very weak lights the step response fell below the predicted curve at times longer than about 2 sec.

4. The step sensitivity defined from the initial peak of the response to a step of light was 2‐6 mV photoisomerization−1 sec, about 1000 times greater than the most sensitive cones in the turtle retina.

5. The response to a small weakly illuminated spot (radius 21 μm) reached a peak later and lasted longer than the linear response to a weakly illuminated large area (radius 570 μm).

6. The difference in sensitivity between large and small spots was reasonably consistent with the apparent space constant of the rod network obtained from the exponential decline of the flash response on either side of an illuminated strip.

7. As others have found, strong flashes did not give an initial hyperpolarizing transient when the radius of the spot was less than about 50 μm.

8. Experiments made by flashing long narrow strips of light onto the retina showed that the response spread a long way initially (λ ≑ 70 μm) and then contracted down to a relatively small region (λ ≑ 25 μm) at times of about 2 sec. When the line source was at some distance from the impaled rod the response reached a peak earlier and was shorter than when the source was close.

9. The results in (8) can be explained quantitatively by assuming that delayed voltage‐dependent conductance changes mimic an inductance and make the rod network behave like a high‐pass filter with series resistance and parallel inductance.

10. In sensitive rods, flash responses varied randomly with a variance which was about 1/30 of that expected in an isolated cell; this reduction in noise is satisfactorily explained by electrical coupling between rods.

11. The variance peak usually occurred later than the potential peak of the rod response.

12. The high‐pass filter characteristics of the rod‐network help to explain several puzzling features of the behaviour of rods, for example (1), (5), (7), (8) and (11) of this summary.

13. The high‐pass filter characteristics of the rod‐network may help it to optimize the signal to noise ratio by integrating over a large area for rapid signals and over a small one for slow signals.
Origin of the humoral factor responsible for compensatory renal hypertrophy
Authors: Dicker S. E. , Morris Christine A.
Published: December 2014

1. Rats were unilaterally nephrectomized and the remaining kidney was removed 10 min after the operation.

2. Cortical slices from both kidneys were incubated in culture medium in the presence of freeze‐dried plasma from a control animal, for 4 hr. When renal cortical slices from a normal animal were now added to and incubated in the medium in which cortical slices from the remaining kidney (i.e. the kidney removed 10 min after unilateral nephrectomy) had been incubated, they showed an increase of protein content and dry weight. This increase did not occur when slices from normal kidneys were incubated in culture medium in which the first kidney had been incubated.

3. The increase of protein content and dry weight of cortical slices from normal kidneys did not occur when incubated in culture medium in which cortical slices from the remaining kidney had been incubated when freeze‐dried plasma from normal rats had been substituted by freeze‐dried plasma from anephric rats.

4. Since normal plasma which does not normally promote protein accretion in normal cortical slices in vitro can do so after it has been incubated with cortical slices from a kidney removed 10 min after unilateral nephrectomy, it is suggested that normal plasma contains a precursor of renal origin which is ‘activated’ when in the presence of a remaining kidney removed shortly after unilateral nephrectomy.