bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of Ca2+ mobilization by caffeine in a cultured vascular smooth muscle cell line (A7r5)
Authors: Otun H , Gillespie JI , Greenwell  , Dunlop W
Published: December 2014

The effects of caffeine on the resting level and agonist‐induced changes in intracellular calcium ([Ca2+]i) have been studied in the vascular smooth muscle cell line A7r5. Caffeine (1‐30 mM) lowers the resting [Ca2+]i by reducing the entry of Ca2+ and inhibits completely the mobilization of Ca2+ by arginine vasopressin. Application of forskolin, to elevate cAMP, does not affect the resting level of Ca2+i but does abolish the agonist‐induced rise. These data add to the complexity of caffeine‐induced changes in [Ca2+]i and point to a possible interaction between cAMP and other second messenger systems mobilizing Ca2+i in this cell type.
Albumin escape from microvessels in kidney, heart and skeletal muscle in experimental diabetes mellitus in the anaesthetized rat
Authors: Pinter GG , Lightman SL , Wilson PD , Yuen L , Bradbury MW
Published: December 2014

Diabetes was induced with streptozotocin in rats weighing about 160 g. These were maintained with age‐matched controls for up to 14 months, blood glucose being periodically monitored. Half the diabetic and control rats received the aldose reductase inhibitor, Ponalrestat, in their diet. Distribution of volumes of 131I‐albumin (5 min) and 125I‐albumin (100 min) were estimated in various tissues at 3 weeks, 6‐7 months and 13‐14 months of diabetes. The former space was assumed to represent the intravascular plasma space, while the latter was taken to include both the extravascular and intravascular albumin volumes in the kidney. In heart and skeletal muscle, equilibration between the specific activities of extravascular albumin and of plasma albumin was not assumed to be complete at 100 min. In the cortex and medulla of kidney, the extravascular albumin pool increased significantly at 13‐14 months of diabetes (for both, P less than 0.01). Significantly increased entry of albumin into the interstitium occurred at 6 months (P less than 0.05) and at 13‐14 months (P less than 0.01) in skeletal muscle, and at 13‐14 months (P less than 0.05) in heart. The intravascular plasma volumes were not influenced by diabetes and the aldose reductase inhibitor had no effect at any time in either diabetic or control rats. These findings indicate increased movement of plasma albumin into the interstitium in the late phase of diabetes in the heart, skeletal muscle and in the kidney. Enlargement of the interstitial albumin pool is likely to affect the fluid balance between capillary and interstitium and may contribute to the effect of diabetes on the function of these organs.
Non‐adrenergic, non‐cholinergic inhibitory responses to nerve stimulation in rat colonic circular muscle
Authors: Serio R , Mule F , Postorino A
Published: December 2014

The nerve‐mediated response to electrical field stimulation (EFS) in rat colonic circular muscle was investigated using the single sucrose‐gap technique. EFS with a single pulse (0.4 ms, supramaximal voltage) elicited transient TTX‐sensitive hyperpolarization (IJP) often followed by an ‘off’ depolarization associated with muscular contraction. No relaxation associated with the IJP could be seen unless tone was pharmacologically induced by carbachol (10(−6) M). IJPs were due to non‐adrenergic, non‐cholinergic (NANC) nerve activation since they were not affected by atropine (10(−7) M) or guanethidine (10(−6) M) superfusion. The mechanism underlying the IJP was presumably an increase in K+ conductance, and the NANC neurotransmitter might open largely apamin‐sensitive, Ca(2+)‐dependent K+ channels. Purines or vasoactive intestinal polypeptide (VIP) did not mimic the effects of NANC nerve stimulation. Therefore, the NANC inhibitory system, producing IJPs, in rat colonic circular muscle is not purinergic or VIPergic in nature.
Inactivation of Ca current during the action potential in guinea‐pig ventricular myocytes
Authors: White E , Terrar DA
Published: December 2014

The inactivation of Ca channels during the action potential plateau of guinea‐pig ventricular myocytes was investigated by interrupting action potentials with voltage clamp pulses to assess Ca channel availability. The influence of the bulk cytosolic calcium [( Ca]i) transient on Ca channel inactivation was also studied by impaling cells with microelectrodes containing the Ca chelator BAPTA (1,2 bis(2‐aminophenoxy)ethane‐N,N,N',N'‐tetraacetic acid; 125‐200 mM). Ca channel availability decreased progressively with action potential duration, reaching approximately 20% of maximum availability after 100 ms and falling close to zero at the end of the plateau. When membrane potential became more negative than ‐40 mV Ca channel availability increased. Elevation of the action potential plateau to more positive levels increased Ca channel availability (even though this was expected to increase peak [Ca]i). When the cytosol was loaded with BAPTA Ca channel availability during the plateau increased. Inactivation of Ca channels was not, however, abolished. The observations are consistent with the hypothesis that in guinea‐pig ventricular myocytes the majority of Ca channels are inactivated during the plateau and recovery does not occur until repolarization is almost complete. It may be that while the cytosolic Ca transient (that is generated in part by release of Ca from the intracellular Ca stores) modulates Ca channel availability, significant inactivation of the Ca channel during the action potential plateau is due to voltage dependent inactivation and to Ca‐induced inactivation resulting from the Ca which enters the myocyte via Ca channels.
The determination of short‐term breast volume changes and the rate of synthesis of human milk using computerized breast measurement
Authors: Daly SE , Kent JC , Huynh DQ , Owens RA , Alexander BF , Ng KC , Hartmann PE
Published: December 2014

The feasibility of using sequential breast volume measurements as a method of studying short‐term rates of milk synthesis in women has been established. We have developed a rapid Computerized Breast Measurement system for the determination of breast volume, based upon the Shape Measurement System. A circle encompassing all the breast tissue is drawn in black face paint on the subject's skin. Six patterns of sixty‐four horizontal light stripes are projected onto the breast and chest wall surface. A CCD camera relays video images to a computer, which produces a model of the chest by active triangulation. The volume of the breast and the chest wall segment enclosed by the circle is then calculated. The precision of the method was dependent upon the subject repositioning carefully. The coefficient of variation of replicate measurements was 1.6%. The accuracy of the method was established by comparing the change in breast volume before and after a breast‐feed with the amount of milk removed by the infant as determined by test weighing. There was a close relationship between the removal of milk by the infant (x) and the change in breast volume (y), (r = 0.93, n = 73, y = 1.10x ‐ 3.25). The rates of milk synthesis between breast‐feeds, for six women determined on one to eight occasions, varied from 11 to 58 ml/h. The results show that the amount of milk available in the breast is not necessarily an important determinant of the amount of milk removed by the infant at a breast‐feed.
The effects of metabolic inhibition and acidification on force production in the rat uterus
Authors: Wray S , Duggins K , Iles R , Nyman L , Osman V
Published: December 2014

The effects of hypoxia and intracellular acidification were examined on the mechanical properties of the non‐pregnant and pregnant rat uterus. Isolated uteri were investigated during control conditions and in the presence of cyanide, to simulate hypoxia or the salts of weak acids and bases to change intracellular pH at constant external pH (pH 7.4). Both spontaneous contractions and high‐K contractures (i.e. fully activated preparations) were investigated at 37 degrees C. In control solutions both pregnant and non‐pregnant uteri were spontaneously active and gave a contracture when bathed with a high‐K+ solution. When oxidative phosphorylation was inhibited by cyanide, spontaneous contractions were either greatly reduced or abolished. The effects on spontaneous contractions were more pronounced in the non‐pregnant than the pregnant uterus. If high‐K solution was added after cyanide had abolished spontaneous contractions, then a small amount of force was produced. High‐K‐induced contractures were not maintained in the presence of cyanide and quickly fell to baseline levels in both pregnant and non‐pregnant uteri. All the effects of cyanide were fully reversible. When only intracellular pH was changed by adding weak acids (50 mM‐butyrate or propionate), spontaneous contractions were greatly diminished or abolished in both pregnant and non‐pregnant uteri. However, the application of weak acids had no effect upon the KCl‐induced contractures in both pregnant and non‐pregnant uteri. The effects of cyanide on the uterus include both an acidification and changes in metabolites, e.g. a fall in [ATP]. To investigate the changes in metabolites without a change in pHi, cyanide was applied with the weak base trimethylamine (40–50 mM). 31P Nuclear magnetic resonance spectroscopy was used to show that the alkalinization which occurs with trimethylamine alone abolished the acidification ordinarily associated with cyanide. Spontaneous and high‐K‐induced contractions were greatly reduced or abolished, i.e. the result was the same as with cyanide alone. This occurred in both pregnant and non‐pregnant uteri. It is concluded that spontaneous force production is affected by both changes in metabolites (e.g. decreased [ATP] and increased inorganic phosphate) and pHi, and that both can depress activation of the uterus. Only the changes in metabolites can depress force production in fully activated preparation. The greater effect on force in the non‐pregnant uterus compared to the pregnant uterus may be due to the lower initial levels of [ATP] and the greater fall in ATP seen in non‐pregnant compared to pregnant uterus, and gestational changes in metabolism.(ABSTRACT TRUNCATED AT 400 WORDS)
Pathobiological reactions of C‐fibre primary sensory neurones to peripheral nerve injury
Authors: Jancso G
Published: December 2014

Mammalian primary sensory neurones display profound anatomical and chemical changes in response to injury of their peripheral processes. Peripheral nerve damage results in transganglionic degeneration of central terminals of A‐fibre primary afferent neurones terminating in the deeper layers of the medullary or spinal dorsal horn. The depletion of neuropeptides and other neurone‐specific macromolecules from neurones in sensory ganglia and from the superficial dorsal horn, the known central projection area of C‐fibre primary afferents, is a salient phenomenon commencing after peripheral nerve lesions. A recently devised new experimental procedure, termed the capsaicin‐gap method, permitted evaluation of the transganglionic degenerative phenomena which develop in C‐fibre primary sensory neurones after a lesion is inflicted upon their peripheral branches. The experimental findings indicated that C‐fibre primary afferent terminals underwent transganglionic degeneration following a perineural treatment with capsaicin, and that this was associated with, and probably resulted from, ganglionic cell degeneration. Studies on the effects of peripheral nerve section yielded similar results. It has therefore been suggested that the observed depletion of specific macromolecules, including sensory peptides, specific glycoconjugates and sensory neurone specific acid phosphatase, may be accounted for, at least in part, by an irreversible loss of sensory ganglion neurones. In contrast, many injured neurones express peptides, including vasoactive intestinal polypeptide, peptide histidine‐isoleucine and galanin, which can be demonstrated in only a few neurones under normal conditions. These seem to be involved in dorsal horn regenerative and/or compensatory processes following peripheral nerve damage. There is suggestive evidence that the partial deafferentation caused by the transganglionic degeneration of C‐fibre primary afferents creates favourable circumstances for an anatomical rearrangement of neuronal connections within the spinal cord dorsal horn. These changes may provide a morphological substrate of some of the functional alterations demonstrated after peripheral nerve lesions.
Evidence for simultaneous bidirectional fluid flux across synovial lining in knee joints of anaesthetized rabbits
Authors: McDonald JN , Levick
Published: December 2014

A recent model predicted a local synovial circulation of extravascular fluid in which capillary filtrate entered a joint cavity and fluid simultaneously drained out of the cavity via intercellular pathways distant from capillaries. Here, solutions of albumin (10–250 g l‐1) were infused continuously into the knee joint cavity in fifteen anaesthetized rabbits at 3–18 cmH2O pressure and steady‐state net trans‐synovial flow was recorded. The intra‐articular fluid collected after 15–30 min was substantially diluted despite a sustained net efflux from the cavity. This supports the prediction that net efflux comprises an influx of low‐protein plasma ultrafiltrate and a larger efflux of joint fluid.
Inhibition of vasopressin and aldosterone release by atrial natriuretic peptide in conscious rabbits
Authors: Gerstberger R , Schutz H , Luther‐Dyroff D , Keil R , Simon E
Published: December 2014

To elucidate the regulatory role of atrial natriuretic factor (ANF) on vasopressin (AVP) and aldosterone release in conscious rabbits, ANF was administered systematically at a rate of 15 pmol min‐1 (kg body wt)‐1 for 15 min in two series of experimental animals in which AVP and/or aldosterone production was stimulated. In euhydrated rabbits (series I), systemic administration of angiotensin II (Ang II) (10 pmol min‐1 (kg body wt)‐1, 15 min) stimulated aldosterone release threefold from basal plasma concentrations (140 pg ml‐1). The co‐application of ANF inhibited the Ang II‐induced release of aldosterone without influencing the non‐stimulated AVP system. In dehydrated rabbits (series II) with elevated plasma osmolality and AVP concentration, exogenously applied ANF increased plasma ANF fourfold at marginally reduced arterial pressure. Plasma AVP concentrations were reduced by 3.4 pg ml‐1 (25%) on average, and plasma aldosterone concentrations were lowered by 34 pg ml‐1 (23%) at unchanged levels of plasma corticosterone. Receptor binding studies using [125I]ANF as radioligand revealed Ang II‐independent high‐affinity receptors for ANF in the zona glomerulosa of the adrenal gland. With regard to the hypothalamo‐neurohypophyseal AVP system, ANF binding sites were localized to the median eminence and neurohypophysis, but not to the magnocellular nuclei. ANF receptors were also labelled in structures lacking a blood‐brain barrier such as the subfornical organ and the choroid plexus.
Rate dependence of action potential duration and calcium current in isolated guinea‐pig cardiocytes
Authors: Peineau N , Garnier D , Argibay JA
Published: December 2014

The duration of the action potential at 50% of its amplitude (APD50) and peak calcium currents (ICa) was measured in single cardiac guinea‐pig ventricular cells, using the whole‐cell patch‐clamp technique in current‐clamp and voltage‐clamp modes respectively. In the absence of intracellular calcium buffer, pacing at 0.28 Hz from a rest period of 1‐2 min induced a transient increase (15.5 +/− 3.5%) in APD50, followed by a gradual shortening. Switching from 0.28 to 0.75 Hz again induced a transient increase of APD50 (6.8 +/− 2.9%). In the presence of EGTA or BAPTA on the cytosolic side of the membrane, this transient phase was prolonged and its amplitude slightly increased (10.6% when switching from 0.28 to 0.75 Hz in 5 mM‐BAPA). The same increase in rate induced either a negative or a positive staircase of ICa, depending on the holding potential. At a holding potential of ‐80 mV, ICa peak was enhanced and the inactivation kinetics was slowed down. This facilitation of ICa seems to be dependent on calcium ions entering the cell via the calcium channels and could partly explain the observed transient increase in APD50.
Muscle glycogen and glucose uptake during exercise in humans
Authors: Hargreaves M , Meredith I , Jennings GL
Published: December 2014

Six men were studied during 40 min of cycling exercise to examine the relationship between leg glucose uptake and muscle glycogen concentration. Exercise resulted in significant increases in leg glucose uptake, while muscle glycogen and arterial blood glucose concentrations declined. Arterial plasma insulin levels did not change significantly. There was a significant inverse relationship between muscle glycogen concentration and glucose uptake during exercise which suggests a possible regulatory influence of muscle glycogen on glucose uptake in the early stages of exercise in humans.
Enhanced electrogenic secretion in vitro by small intestine from glucagon‐treated rats: implications for the diarrhoea of starvation
Authors: Lane A , Levin RJ
Published: December 2014

Glucagon treatment of fed rats (50 micrograms I.P. every 6 h for 3 days) induces significant increases in vitro of the basal short‐circuit currents of the jejunum (52%) and proximal ileum (81%) and in their electrogenic secretory responses to stimulation by bethanechol, a muscarinic agonist. The results support a role for glucagon in the intestinal hypersecretion observed in starvation and nutrient deprivation.
Hepatic regulation of renal function
Authors: Lang F , Tschernko E , Haussinger D
Published: December 2014

Despite apparently conflicting reports in the past, the bulk of evidence presently available points to a significant role for the liver in the regulation of renal function. Hepatic regulation of renal function may involve both a hepatorenal reflex and a liver‐borne diuretic factor (LBDF and/or ‘glomerulopressin’). The hepatorenal reflex is elicited by an increase in intrahepatic pressure, and/or certain amino acids in portal venous blood. It is transmitted by serotonin in the liver and presumably by noradrenaline in the kidney. It leads to a marked decrease in renal blood flow, glomerular filtration and urinary flow rate. The evidence for the LBDF is still circumstantial. The LBDF may be stimulated by glucagon and adenosine. It leads to a marked increase of renal blood flow, glomerular filtration rate and urinary output. Amongst the conditions presumed to be associated with altered hepatic regulation of renal function are postprandial hyperfiltration, and the deterioration of renal function which occurs in liver disease, cardiac insufficiency and cardiovascular shock.
Polyol pathway‐mediated changes in cardiac muscle contractile properties: studies in streptozotocin‐diabetic and galactose‐fed rats
Authors: Cotter MA , Cameron NE , Robertson S
Published: December 2014

Contractile properties of left ventricular papillary muscles and atria from streptozotocin‐diabetic and from non‐diabetic rats fed a 40% galactose diet were measured in vitro. There was a characteristic slowing of twitch responses for both tissues and both treatments (P < 0.05). Time to peak contraction was prolonged by 18‐33% and maximum rate of contraction was reduced by 10‐17%. Relaxation was also affected, with a 13‐37% increase in half‐relaxation time and a 7‐25% reduction in the maximum rate of relaxation. There were treatment differences between papillary muscles and left atrium, diabetes having a more marked effect on the former, whereas galactosaemia caused more pronounced changes in the latter. The resting beat rate of the right atrium was 22% reduced in diabetic and galactosaemic rats (P < 0.01). When maximally stimulated with isoprenaline, beat rate did not rise to the level of stimulated controls (P < 0.01). Papillary muscle speed‐related contractile properties also showed a reduced response to isoprenaline in diabetic and galactosaemic groups compared to normal controls. The greatest deficit was found for maximum rate of relaxation where responsiveness was 41 and 34% less for diabetic and galactosaemic groups respectively (P < 0.01). Polyol pathway metabolites in diabetic ventricles were increased 8‐fold. In galactosaemic rats galactitol accumulation led to a 530‐fold increase in polyols. The data suggest that polyol pathway activity may be an important factor in the aetiology of contractile and chronotropic changes in diabetic and galactosaemic cardiomyopathy.
Polyol pathway‐related skeletal muscle contractile and morphological abnormalities in diabetic rats
Authors: Cotter MA , Cameron NE , Robertson S , Ewing I
Published: December 2014

This study examined the effect of inhibition of aldose reductase, the first enzyme in the polyol pathway, on fast and slow twitch skeletal muscle morphology and function in streptozotocin‐induced diabetes in rats. There was a preventative investigation with diabetes duration of 4 months, and a reversal investigation where treatment was given for 2 months following an untreated period of 2 months. For slow twitch soleus muscle, contractions were prolonged by diabetes, and this was partially prevented but not reversed by treatment. Relaxation was profoundly slowed, and both prevention and reversal ameliorated the changes. Diabetes had minimal effects on tension production for soleus. However, for fast twitch extensor digitorum longus, although there was little effect on speed‐related contractile parameters, tetanic tension production was progressively reduced with diabetes duration. This effect was antagonized by treatment. Soleus fatigue resistance was markedly reduced by diabetes, but restored to normal by treatment. There was a reduction in oxidative enzyme staining (succinic dehydrogenase), and capillary‐fibre ratio, both of which were ameliorated by aldose reductase inhibition. Mean soleus fibre area was reduced after 4 months of diabetes, and this was prevented but not reversed by treatment. Fibre area was also reduced in extensor digitorum longus, particularly for fast glycolytic fibres. There was a small amelioration with treatment. It is concluded that enhanced polyol pathway activity makes a contribution to diabetic myopathy, and that aldose reductase inhibitors can prevent this by actions on muscle fibres and their vascular supply.
Effects of acute acid loading on parathyroid hormone secretion and on urinary calcium and cAMP excretion in the growing lamb
Authors: Scott D , Loveridge N , Abu Damir H , Buchan W , Milne J
Published: December 2014

Growing lambs fed a diet containing NaHCO3 were made acidotic by intravenously infusing HCl at the rate of 1 mmol/min over a 4 h period. Acid infusion led to a fall in blood and urine pH and a prompt increase in urinary Ca excretion. This in turn led to a fall in plasma Ca concentration and a rise in parathyroid hormone (PTH) levels. Urinary cAMP excretion was unaffected by acid infusion. In separate experiments lambs made acidotic by feeding a diet containing NH4Cl were given infusions of PTH at the rate of 1 microgram/h. Infusion of the hormone was accompanied by a rise in plasma Ca and an increase rather than a decrease in urinary Ca excretion and no change in urinary cAMP excretion. These results point to the kidney as the primary site of response to acid loading in the lamb, a failure to reabsorb Ca in these conditions necessitating the release of PTH and an increase in bone resorption in order to maintain normal plasma Ca levels.
Effects of D‐glucose, L‐glucose and D‐mannitol on renal calcium handling and general renal function in the rat
Authors: Boland PS , Garland HO
Published: December 2014

Standard renal clearance techniques were used to compare the effects of D‐glucose, L‐glucose and D‐mannitol on renal calcium handling and general renal function in the anaesthetized rat. A significant (P < 0.01) calciuresis was seen in animals infused with D‐glucose. This resulted from a decreased tubular reabsorption of calcium. A similar response was not seen with L‐glucose or D‐mannitol. The contrasting actions of the three sugars on tubular calcium transport may relate to their different transport characteristics, since only D‐glucose is actively reabsorbed. Responses of the three sugars also differed with respect to fractional fluid and sodium reabsorption which were significantly (P < 0.001) lower in animals infused with L‐glucose and D‐mannitol, and plasma insulin concentrations which were significantly (P < 0.01) elevated only in the D‐glucose group. An unexpected finding was a highly significant (P < 0.001) and progressive fall in glomerular filtration rate (GFR) in animals infused with L‐glucose. The reasons for this are not known.
Renal micropuncture study of the effects of D‐glucose tubular calcium handling in the anaesthetized rat
Authors: Boland PS , Garland HO
Published: December 2014

Tracer microinjection studies were used to grossly locate the nephron site of altered calcium transport following D‐glucose loading. Superficial proximal and distal nephrons were injected with a solution containing 45Ca and either D‐glucose or L‐glucose (as control). Tubule calcium transport was assessed from the recovery of radioactivity in the final urine. 45Ca recoveries from early proximal microinjections were comparable in the two groups (2.63 +/− 0.68 vs. 3.70 +/− 1.19%). However, 45Ca recoveries from late proximal microinjections were significantly higher than D‐glucose was included in the injectate (7.39 +/− 1.34 vs. 2.83 +/− 0.67%, P < 0.05). 45Ca recoveries from distal microinjections were also significantly higher in the D‐glucose group (87.6 +/− 2.43 vs. 71.0 +/− 2.92%, P < 0.001). These data suggest that the effects of D‐glucose on renal calcium handling are mediated at the level of the distal tubule, thick ascending limb of the loop of Henle and/or pars recta. The precise mechanisms involved are not known.
The short‐term synthesis and infant‐regulated removal of milk in lactating women
Authors: Daly SE , Owens RA , Hartmann PE
Published: December 2014

We studied how short‐term milk synthesis responds to milk removal by observing breast volume before and after each breastfeed over 24 h periods within the homes of seven lactating mothers, using the Computerized Breast Measurement system. Short‐term rates of milk synthesis varied markedly between the breasts of individual mothers, varied markedly between interfeed intervals for individual breasts and, for six of the thirteen breasts studied, were positively related to the degree to which the breast was emptied (r2 ranging from 0.32 to 0.95). In addition, the infants rarely emptied the breasts of available milk (mean +/− S.D. of degree of emptying postfeed = 76 +/− 20%, n = 147) and, within women, storage capacity of a breast was related to the demand for milk from that breast (r2 = 0.91, P < 0.0001). It was concluded that the infants were self‐regulating their milk intake. Furthermore, the storage capacity of the breast, variations in the short‐term rates of milk synthesis and responsiveness of milk synthesis to the degree of breast emptying provided mechanisms whereby maternal milk supply could be directly linked to infant demand. Our findings are discussed with reference to the autocrine control of milk synthesis.
Evidence for decrease in myofilament responsiveness to Ca2+ during hypoxia in spontaneously active vascular smooth muscle in rats
Authors: Soloviev AI , Basilyuk OV
Published: December 2014

The cellular mechanisms underlying smooth muscle hypoxic relaxation were examined in experiments on isolated chemically skinned muscle strips of rat portal vein. Low PO2 (3.9 kPa) shifted the pCa‐tension relation to the right by 0.29 +/− 0.01 pCa units as compared to control curves (PO2, 18.8 kPa). Thus the Ca2+ sensitivity of the filaments had decreased. Addition of cyclic AMP (30 mumol l‐1) with theophylline (5 mmol l‐1) to the buffer solution produced a similar shift to low PO2. Low PO2 also decreased the maximal force to 40‐50% of control. Inclusion of sodium fluoride (10 mmol l‐1) and aluminium chloride (10 mumol l‐1) in a bath solution caused partial (25‐30%) relaxation of skinned smooth muscle preconstricted with 10 mumol l‐1 Ca2+. The rate and amplitude of smooth muscle relaxation at low PO2 were significantly decreased by tolbutamide (5 mmol l‐1), which is known to inhibit cyclic AMP‐dependent protein kinases. We suggest that PO2 changes can alter myofilament responsiveness to Ca2+ and this effect may be related to cyclic AMP‐dependent phosphorylation of myosin light chain kinase, its inactivation and subsequent uncoupling between Ca2+ and contractile machinery in smooth muscle.
Mechanism of pregnancy‐induced attenuation of contraction to phenylephrine in rat aorta
Authors: Aloamaka CP , Ezimokhai M , Cherian T , Morrison J
Published: December 2014

The role of endothelium in the decreased contraction to phenylephrine in aorta of pregnant Wistar rats has been studied. Contractions in response to phenylephrine were significantly decreased in aortic rings from pregnant rats compared to those from non‐pregnant rats. Pretreatment of the rings with indomethacin did not significantly alter the pattern of responses. When endothelium was removed from the rings, contractions of rings from non‐pregnant rats were similar to those from pregnant rats. Acetylcholine‐induced relaxations of rings from pregnant and non‐pregnant rats precontracted with phenylephrine were not significantly different. The results suggest that in the rat aorta and under in vitro conditions, pregnancy‐induced attenuation of contraction to phenylephrine is, at least partly, endothelium dependent and that the release of the endothelium factor responsible for this alteration in response may be indomethacin insensitive.
A comparison of the mechanogram of the ankle jerk in men and women: observations using an adjustable dorsiflexing torque, high inertia mechanical filter and automatic readout system
Authors: Walsh EG , Wright GW , Davies A , Lin JP , Thompson J
Published: December 2014

An instrument of new design has been constructed to measure the contractions of the calf musculature resulting from a tap on the Achilles tendon. The instrument provides a predetermined and adjustable dorsiflexing torque from a printed motor, but the contractions are virtually isometric as the system is one of high inertia. Peak force, half‐contraction time and half‐relaxation time are monitored by electronic circuits equipped with digital output meters. Observations have been made on fifty‐two male and forty‐five female medical students. There were no significant differences in the peak torques generated by the contractions between the men and women students and no difference in the half‐contraction times. The half‐relaxation times of the women were, however, significantly longer than those of the men (P = 0.0001). In another group of students the EMG discharges following a tendon tap were recorded, there was no significant difference in the duration of the activity in men and women. Observations have also been made on twenty‐three male and seventy female subjects whose mean ages were in the mid‐sixties. The peak torques generated by the contractions were significantly higher in the women (P = 0.03). There was no difference in the half‐contraction times, but the half‐relaxation times of the women were significantly longer (P = 0.001). Possible reasons for the differences are discussed.
Nitric oxide modulates sympathetic vasoconstriction and basal blood flow in normal and acutely inflamed rabbit knee joints
Authors: Najafipour H , Ferrell WR
Published: December 2014

Experiments were performed to investigate the role of nitric oxide (NO) in the regulation of joint blood flow and in modulating sympathetic vasoconstrictor influences in normal and acutely inflamed rabbit knees. Close intra‐arterial infusion of N omega‐nitro_L‐arginine methyl ester (L‐NAME), a NO production inhibitor, reduced basal joint blood flow, measured by laser Doppler flowmetry, by 36.4 +/− 5.1% (mean +/− S.E.M.) in normal (control) and 21.4 +/− 7.8% in carrageenan‐inflamed knee joints. Mean systemic arterial blood pressure was increased by 20 +/− 3.1 and 17.9 +/− 2% in control and test animal groups respectively. Joint vascular resistance was increased by 101 +/− 19% in normal and 68.9 +/− 13.7% in carrageenan‐treated animals. Vasoconstrictor responses to electrical stimulation of the posterior articular nerve (PAN) were significantly smaller in the inflamed joint compared to normal. Infusion of L‐NAME for 45 min resulted in an increased vasoconstrictor response by 78% in normal and 79% in inflamed joints. Subsequent close intra‐arterial infusion of L‐arginine failed to return the enhanced vasoconstrictor responses induced by L‐NAME to their control levels in both normal and test animal groups, but partially restored blood flow changes. In both normal and inflamed joints, vasoconstriction produced by separate intra‐arterial injection of the alpha 1‐agonist phenylephrine (2.5 nmol) or either of the alpha 2‐agonists clonidine (250 pmol) and UK‐14304 (250 pmol) was increased significantly by L‐NAME infusion but not completely restored to basal values by L‐arginine infusion. The control responses to all three agents did not differ significantly between normal and inflamed knees.(ABSTRACT TRUNCATED AT 250 WORDS)
Rhythmicity associated with a high degree of short‐term synchrony of motor unit discharge in man
Authors: Davey NJ , Ellaway PH , Baker  , Friedland CL
Published: December 2014

A rhythmic modulation of motor unit discharge at 17–24 Hz has been observed in the tibialis anterior muscle of subjects who display a high degree of short‐term synchrony. Motor unit discharges were recorded both from extensor digitorum communis in the arm and tibialis anterior in the leg during voluntary isometric contractions. Time domain analysis of motor unit discharges in both muscles revealed a prominent central peak in the cross‐correlograms that was interpreted as short‐term synchrony. In tibialis anterior, but not in extensor digitorum communis, the primary, central peak was accompanied by secondary peaks. These were symmetrically or unilaterally present at an average time lag of 52 ms (range 37–68 ms) with respect to the primary peak. In both muscles other peaks occurred at time lags equivalent to the mean interspike interval of motor unit discharge (range 80‐150 ms). In all subjects frequency domain analysis of the discharges of pairs of motor units revealed prominent peaks of coherence in the range 17–24 Hz. The actual frequency matched closely the reciprocal of the time lag interval between primary and secondary peaks of the cross‐correlogram of the same motor units. Coherence was less evident for motor unit discharges in extensor digitorum communis and no prominent peaks occurred in the range 17–24 Hz. We propose that the secondary peaks and the rhythmicity may involve recurrent inhibition activated by the synchronous discharge of motor units. The presence of this pattern of discharge in tibilias anterior but not extensor digitorum communis would fit with recent animal and human work suggesting that recurrent inhibition is poorly represented in certain distal muscles of the forelimb.
The effect of the putative AT2 agonist, p‐aminophenylalanine6 angiotensin II, on thirst and sodium appetite in rats
Authors: Cooney AS , Fitzsimons JT
Published: December 2014

Intracerebroventricular injection of the putative AT2 agonist, p‐aminophenylalanine6 angiotensin II (p‐NH2Phe6‐Ang II), caused dose‐dependent increases in intakes of water and NaCl similar to those produced by angiotensin II but requiring more than one thousand times the dose. Very large doses of another AT2 agonist, angiotensin(1‐7) heptapeptide (Ang(1‐7)), had no effect on intakes of water and NaCl up to 24 h after injection, nor did Ang(1‐7) affect angiotensin II‐induced drinking when the two peptides were given together. The AT1 antagonist, losartan, but not the AT2 antagonist, CGP 42112B, inhibited p‐NH2Phe6‐Ang II‐ and angiotensin II‐induced drinking, suggesting that p‐NH2Phe6‐Ang II, like angiotensin II, acts on AT1 but not AT2 receptors. However, large doses of the AT2 antagonist, PD 123319, inhibited drinking in response to both dipsogens. Since p‐NH2Phe6‐Ang II‐ and angiotensin II‐induced drinking were unaffected by CGP 42112B, this could mean that there are different AT2 receptor subtypes of which only the PD 123319‐sensitive one is involved in drinking. But because of the very large doses of PD 123319 used it is also likely that there was loss of receptor specificity resulting in cross‐reaction of PD 123319 with AT1 receptors. The results do not favour involvement of AT2 receptors in angiotensin‐induced thirst and sodium appetite in the short term.
Acute systemic hypoxia and the surface ultrastructure and morphological characteristics of rat leucocytes
Authors: Mian R , Westwood D , Stanley P , Marshall JM , Coote JH
Published: December 2014

We have examined the surface ultrastructure and morphological characteristics of leucocytes obtained from control rats breathing air and rats made acutely hypoxic (breathing 6% O2, for 30 min). Striking ultrastructural and morphological changes occurred in the leucocytes of hypoxic rats. These changes included the appearance of crater‐like holes, a reduction in granule size and disruption of the cell membrane. The implications of these findings are discussed.
Heat stress increases ammonia accumulation during exercise in humans
Authors: Snow RJ , Febbraio MA , Carey MF , Hargreaves M
Published: December 2014

Seven men were studied during 40 min of exercise at 70% VO2 peak, in an environmental chamber maintained at either 20 or 40 degrees C, to examine the effect of heat stress on ammonia metabolism during exercise. Heart rate and rectal and muscle temperatures were higher during exercise in the heat, while no differences were observed in pulmonary oxygen uptake or respiratory exchange ratio. Plasma ammonia levels and muscle ammonia accumulation were higher during exercise at 40 degrees C compared with 20 degrees C. Such metabolic alterations may be associated with reduced performance during exercise in the heat.
Effect of intestinal resection, type of dietary fat and time on biliary lipid secretion in rats
Authors: Gomez-Ayala AE , Lisbona F , Lopez-Aliaga I , Barrionuevo M , Pallares I , Alferez MJ , Hartiti S , Campos MS
Published: December 2014

The effects of time and the type of dietary fat on biliary physiology in rats with 50% resection of the distal small intestine were investigated. The effects of ursodeoxycholic acid as an exogenous source of bile acid added to the diet were also studied. The fat composition of all diets was the same in quantitative terms (4%), and differed only in the type of lipid supplied: olive oil (diet A) or one‐third medium chain triglycerides, one‐third sunflower seed oil and one‐third olive oil (diet B). In resected rats given diet A for 1 or 3 months, there was a decrease in biliary secretion of cholesterol and phospholipids, and in the lithogenic index, with respect to the control group. Resected rats fed diet B for 1 or 3 months showed increases in biliary secretion of cholesterol and phospholipids, and in the lithogenic index, in comparison with resected rats fed diet A. The addition of ursodeoxycholic acid to diet B led to the decoupling of bile acid and bile lipid secretion.
Glucose and L‐lactate metabolism in pregnant and in lactating ewes fed barley‐ or ground maize‐based diets
Authors: Perry KW , Janes AN , Weekes TE , Parker DS , Armstrong DG
Published: December 2014

The contribution of glucose absorbed from the small intestine to whole‐body glucose metabolism was examined in ewes during late pregnancy and early lactation, using diets based on ground barley or ground maize. Glucose and L‐lactate turnover in the whole body and the mesenteric‐drained viscera were investigated in these ewes using isotope dilution techniques. The net absorption of glucose by the mesenteric‐drained viscera and whole‐body glucose turnover were unaffected by diet or reproductive status. Arterial and mesenteric venous blood glucose concentrations, arterial and mesenteric venous L‐lactate concentrations and whole‐body lactate turnover were all significantly higher in lactation than in pregnancy. The whole‐body rates of lactate conversion to glucose and to other products were significantly higher in lactation than in pregnancy. Using a two‐pool model of whole‐body glucose and lactate metabolism, a relatively high percentage of glucose was converted to lactate (64–84%), accounting for 60‐80% of whole‐body lactate turnover. A model of glucose and lactate metabolism by the mesenteric‐drained viscera was constructed. Both the calculated endogenous glucose production and the visceral conversion of glucose to lactate were greater in lactation than in pregnancy when barley was fed. Calculated total glucose absorption was relatively constant, contributing between 26 and 59% of whole‐body glucose turnover. Diet had little effect on glucose and lactate metabolism in either the mesenteric‐drained viscera or the whole‐body of breeding ewes.
The effect of lowered pH on the Ca(2+)‐activated contractile characteristics of skeletal muscle fibres from endurance‐trained rats
Authors: Lynch GS , Williams DA
Published: December 2014

The effects of acidosis on the contractile characteristics of single, skinned fast‐ and slow‐twitch skeletal muscle fibres were investigated in both sedentary and endurance‐trained rats. The trained rats were subjected to a long‐term 16 week programme of high‐intensity endurance swimming, and carried a load (corresponding to 2% of body mass) during all 2 h sessions. Intracellular acidification, which has been shown in many studies to contribute to the process of muscular fatigue, was mimicked by lowering the pH (from pH 7.1 to 6.6) of the Ca(2+)‐buffered solutions bathing isolated, skinned (demembranated) muscle fibres. Activation at both levels of pH enabled comparisons between muscle contractile properties under normal and simulated 'fatigue' conditions. Endurance swimming was shown to significantly improve contractile characteristics of single fibres, activated at lowered pH, as evidenced by an increase in Ca2+ sensitivity in the swim‐trained rat muscle fibres compared to those sampled from sedentary control animals. This improvement in contractile properties was demonstrated in both fast‐ and slow‐twitch fibres. It was concluded that the endurance swimming programme significantly improved skinned fibre contractile properties under acidotic conditions.
Role of fetal sac fluids during maternal water deprivation in sheep
Authors: Dickson KA , Harding R
Published: December 2014

Our aim was to determine the importance of amniotic and allantoic fluids for the maintenance of fetal plasma composition during maternal dehydration when water transfer from mother to fetus is likely to be reduced. Eight pregnant ewes were studied before, during and after water deprivation (36 h), firstly with the fetal fluid sacs intact and then with them drained of fluid for 5 days. When water deprivation was combined with drainage, the increases in the osmolalities, [Na+] and [Cl‐] in maternal plasma, in fetal plasma and in lung liquid; the increases in fetal urinary osmolality and [Na+]; and the increases in maternal plasma and fetal plasma arginine vasopressin concentrations were greater than those resulting from water deprivation alone. Our results show that during maternal water deprivation, an absence of fluid in the fetal sacs increases both the osmotic stimulus to the fetus and the fetal responses resulting in conservation of water and salt. We conclude that, when the mother is deprived of water, fluid in the fetal sacs is used to limit the degree of maternal and fetal dehydration.
Carrier‐mediated transport is involved in mucosal succinate uptake by rat large intestine
Authors: Wolffram S , Badertscher M , Scharrer E
Published: December 2014

Mucosal uptake of succinate across the luminal epithelial border in various segments of the large intestine of the rat (proximal and distal colon, caecum) was investigated using an in vitro mucosal uptake technique. For comparison, some experiments with jejunal preparations were also performed. Additionally, disappearance of succinate from the lumen of ligated loops of the proximal and distal colon was measured in vivo. In the ligated loop experiments, the succinate concentration of the instilled solution significantly decreased during a period of 30 min in both colonic segments, indicating absorption of succinate. The in vitro experiments revealed a distinct Na+ dependence of mucosal succinate uptake in all intestinal segments investigated. Because succinate uptake by the colonic mucosa of germ‐free rats was similarly enhanced in the presence of Na+ compared with Na(+)‐free conditions, measured uptake appears to be due to mucosal uptake rather than to Na(+)‐dependent uptake of succinate by bacteria associated with the mucosa. The evaluation of the kinetics of succinate transport in the proximal colon and jejunum, respectively, revealed a single, Na(+)‐dependent saturable component and a diffusive component in both intestinal segments. With respect to the apparent kinetic parameters of the carrier‐mediated transport component, the transport capacity (Vmax) of the jejunal carrier appears to be substantially higher compared with the colonic mechanism (80 and 11 nmol cm‐2 (5 min)‐1, respectively) whereas the affinity constants (Km) did not differ markedly in both segments (0.67 and 0.41 mmol l‐1, respectively). Mucosal uptake of 14C‐labelled succinate in the proximal colon was inhibited by unlabelled succinate, fumarate, citrate and tricarballylate, but not by glutamate, L‐leucine or butyrate. Na(+)‐dependent uptake of the tricarboxylate tricarballylate but not of the dicarboxylate succinate was significantly enhanced by lowering the pH from 7.0 to 5.5, indicating preferential transport of the protonated forms of tricarboxylates. It is concluded from the present results that a Na(+)‐dependent, saturable carrier is involved in the uptake of structurally related tri‐ and dicarboxylates by the colonic mucosa of the rat.
Rectangular hyperbola fitted to muscle force‐velocity data using three‐dimensional regression analysis
Authors: Wohlfart B , Edman KA
Published: December 2014

A simple method is described for fitting a rectangular hyperbola to force‐velocity data derived from active muscle. The approach is based on three‐dimensional regression analysis of the variables force, velocity and (force x velocity). The usage of the method is illustrated by practical applications. A pocket calculator is sufficient for the mathematical treatment.
Presynaptic inhibition by neuropeptide Y of slow inhibitory synaptic transmission in submucous neurones of guinea‐pig caecum
Authors: Cunningham SM , Mihara S , Lees GM
Published: December 2014

The occurrence and disposition of immunoreactivity for neuropeptide Y (NPY) was investigated in the submucosa of guinea‐pig caecum. There were few NPY‐immunoreactive neurones but intraganglionic varicose fibres were so numerous and strongly immunoreactive that some somata may have been obscured. In each neurone tested, exogenous application of NPY (1‐100 nM) depressed the duration and amplitude of the slow inhibitory postsynaptic potential. In contrast, NPY (1‐300 nM) had no effects on the resting membrane potential, input resistance and fast and slow excitatory synaptic transmission.