Showing papers in "Acta Physiologica Scandinavica in 1983"

Mechanical properties of rat cerebral arteries as studied by a sensitive device for recording of mechanical activity in isolated small blood vessels.

Abstract: A sensitive device for recording of mechanical activity in isolated small blood vessels with calibres down to 100 microns is described. This equipment was used to examine the mechanical properties of rat cerebral arteries. The ultrastructure of the preparations was investigated by light-, transmission, and scanning electron-microscopy. In general the walls of the middle cerebral and basilar arteries consisted of 3 layers of smooth muscle cells, which occupied approximately 80% of the total wall thickness. The present technique preserved the integrity of the vessel wall and caused no observable damage to the smooth muscle or endothelial cells. Neither the basilar nor the middle cerebral arteries developed spontaneous phasic contractions under standard conditions. Potassium excess (124 mM) induced a biphasic contractile response characterized by a fast and partly transient increase in tension (phase A), followed by a slowly developing sustained contraction (phase B). The responses to K+ were strong, highly reproducible and not influenced by pH changes in the range 6.9-7.8, making K+-stimulation suitable for testing of vascular contractility. Length-tension measurements were performed on relaxed and K+-activated basilar arteries. The mechanical behaviour of the vessels conformed to a sliding-filament model of muscular contraction. Using the "Maxwell model" of a muscle, the length at which the contractile element produced maximum active tension was established. The passive wall tension at this length (approximately 1 mN/mm) averaged only about 20% of the total wall tension the arteries were capable of producing when activated by K+. Under isometric conditions the K+-contracted basilar artery developed a maximum active wall stress of approximately 240 mN/mm2. In the light of the mechanical data obtained from the length-tension measurements, the optimum resting wall tension for registration of vascular responses is discussed. It appears that the present in vitro system can be of great value in investigations of the smooth muscle function in small blood vessels.

Intracerebral grafting of neuronal cell suspensions. I. Introduction and general methods of preparation.

Abstract: The steps involved in the grafting of mesencephalic and septal embryonic tissue in the form of dissociated cell suspensions are described in detail. This includes dissection of the donor embryos, incubation in trypsin, mechanical dissociation, and stereotaxic injection into the brains of adult recipient rats. Some of the technical problems and limitations are discussed.

Muscle fibre type distribution, muscle cross‐sectional area and maximal voluntary strength in humans

Abstract: The relationship between maximum voluntary concentric strength, muscle fibre type distribution and muscle cross-sectional areas were examined in 23 subjects (7 female and 11 male phys. ed. students as well as 5 male bodybuilders). Maximal knee and elbow extension as well as elbow flexion torque at the angular velocities 30, 90 and 180 degrees per second was measured. Muscle biopsies were taken from vastus lateralis and m. triceps brachii. The muscle cross-sectional area of the thigh and upper arm was measured with computed tomography scanning. The maximal torque correlated strongly to the muscle cross-sectional area times an approximative measure on the lever arm (body height). Maximal tension developed per unit of muscle cross-sectional area did not correlate significantly with per cent type I fibre area and did not differ between the female and male students or bodybuilders. Neither did the relative decrease in torque with increasing contraction velocity show any significant relationship to the per cent type I fibre area. The total number of muscle fibres was estimated by dividing the muscle cross-sectional area with the mean fibre area of m. triceps brachii. The number of fibres did not seem to differ between the sexes.

Peripheral control of the cat's step cycle. II. Entrainment of the central pattern generators for locomotion by sinusoidal hip movements during "fictive locomotion.".

Abstract: Acute low spinal and curarized cats injected with noradrenergic agonists i.v. can elicit an efferent burst pattern which can be recorded in muscle nerve filaments and can be referred to as “fictive locomotion”. This study investigates the effect that feedback, arising from movements in the hip joint, can exert on the central network generating fictive locomotion. The central network is uncoupled from generating any active movements by curarization. The motor pattern could be entrained by applying sinusoidal hip movements, even when a very extensive denervation of the leg had been performed leaving only some of the muscles around the hip and the hip joint innervated. During flexion movements, efferents to different flexor muscles became active and during movements in the reverse direction (extension), efferents to extensors were active. With an increasing movement frequency the onsets of both flexor and extensor bursts were delayed in the movement cycle. The duration of the extensor bursts varied markedly with the movement cycle, whereas pure flexors changed less in burst duration. The frequency range within which the efferent burst activity was entrained in a strict 1:1 relation to the movement varied between 5 to 70% above and below the resting burst period. In preparations with a narrow 1:1 range, a “relative coordination” was encountered outside this range. The flexor burst duration was in these cases dependent on where in the hip movement cycle the bursts appeared.

Distribution of different fibre types in human skeletal muscles. 2. A study of cross-sections of whole m. vastus lateralis.

Abstract: In order to determine the total number of fibres and the extent to which the relative occurrence of different fibre types varies within m. vastus lateralis, 15 micrometers thick cross-sections of whole muscles were prepared. The total number of type 1 and type 2 fibres was determined in every 48th square millimetre of the section, and the results thus obtained were analysed using a computer program allowing an assessment of bivariate data in the form of contour plots. The total number of fibres varied both in proximal to distal direction in the same muscle and between individuals. No obvious correlation existed between the mean fibre area and the muscle cross-sectional area. The proportion of type 1 fibres in the whole muscle varied between individuals (from 44% to 57%) with a mean value for all five of 52%. The distribution of different fibre types varied within the muscle, mainly as a function of depth, with a predominance to type 2 fibres at the surface and type 1 fibres in deeper regions of the muscle. Thus, the fibre type distribution in m. vastus lateralis is not random. This must be taken into consideration when data on fibre type composition are compared with functional variables.

The stride cycle of the cat: the modelling of locomotion by computerized analysis of automatic recordings.

Abstract: The present study gives a general description of the locomotor patterns of the intact cat. Overground and treadmill locomotion were studied by means of automatic recordings of limb movements, ground reaction forces and electromyograms. The data processing and automatic recording techniques which were used are described; one recording technique is based on a television system, another on the Selspot I system. The data were processed and analysed interactively with a computer, which allows a statistical analysis of many strides in a fast and accurate way. The amplitudes and time course of movements in different joints and different limbs were studied at different velocities of locomotion and correlated to each other and to parameters such as the onset and termination of electromyographic activity in different muscles. No element of the stride cycle was found to be constant: The amplitudes of joint angles and limb excursions as well as the durations of the different phases of the stride cycle can be adapted to maintain an appropriate coordination between the limbs. The durations of all phases of the stride cycle decrease with increasing speed of locomotion. The durations of the support and extension phases change proportionally more than of the swing and flexion phases and they all appear to be linearly related to the stride cycle duration. The relations of the flexion duration with the stride cycle duration for the different joints are usually different from each other and after a disturbance of the movements of a forelimb the duration of knee and ankle flexion of the homolateral limb can increase and the first extension phase of knee and ankle decrease, whereas they usually increase or decrease together. This further supports the hypothesis that every joint is controlled by a flexion and extension unit pattern generator. The amplitude of the joint angle excursions during the different phases of the stride cycle are better controlled than the absolute joint angles at the onset and termination of these phases. The position of the toe at touch-down was studied at different velocities of locomotion and was found to remain comparatively constant. There is a correlation between hip, knee and ankle joint angles at touch-down, which was found to be of importance for the precise positioning of the foot.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects and distribution of vagal capsaicin-sensitive substance P neurons with special reference to the trachea and lungs

Abstract: The origin of substance P (SP)-immunoreactive neurons in the lower respiratory tract, esophagus and heart of guinea-pigs was demonstrated by surgical denervation or capsaicin pretreatment with subsequent determination of the tissue levels of SP by radioimmunoassay. In other experiments the effect of vagal nerve stimulation on the SP levels in these tissues was studied. The effects of capsaicin-sensitive afferents in the respiratory tract mucosa and bronchial smooth muscle was also studied by analysis of vascular permeability to Evans blue and insufflation-pressure changes. Our present data indicate that all SP nerves in the trachea and lung are afferent and capsaicin-sensitive. The trachea and stem bronchi receive SP afferents mainly from the right vagus nerve with cell bodies located in both the nodose and jugular ganglia. The SP innervation of the lung seems to have a dual origin: 1. Afferents from both vagal nerves with a crossed type of innervation pattern. 2. A non-vagal source which consists of about 40% of the SP nerves in the lung. These nerves probably originate from thoracic spinal ganglia. The effects of ether and capsaicin on insufflation pressure and increase in vascular permeability were dependent on the integrity of capsaicin-sensitive afferents of both vagal and non-vagal origin. In the guinea pig, systemic capsaicin pretreatment to adult animals seemed to result in irreversible changes in the respiratory tract, while in the rat a successive recovery of the functional response of capsaicin-sensitive afferents occurred. Different regimes of systemic capsaicin pretreatment induced different effects on the cholinergic (atropine-sensitive) insufflation-pressure response. Capsaicin pretreatment, using multiple injections over two days, depressed the cholinergic insufflation-pressure increase, while the cholinergic vagal component was unaffected in animals which received a single dose of capsaicin or local pretreatment with capsaicin on the vagal nerves. The local treatment was more effective with regard to SP depletion in target areas when using alcohol as solvent than when capsaicin was dissolved in paraffin oil, while the functional deficits were similar. The SP nerves in the esophagus were mainly of vagal afferent origin, while the heart atrium seemed to have a dual innervation by both vagal and non-vagal SP nerves.

Substance P and capsaicin-induced contraction of human bronchi

Abstract: Substance P induced a dose-dependent contraction of human segmental bronchi in vitro with a threshold dose of about 10(-6) M. These preparations were obtained from patients undergoing lung tumor surgery. The substance P-induced contractions were resistant to mepyramine and atropine, suggesting a direct effect on the bronchial smooth muscle. Capsaicin (10(-5) M) also induced a slowly developing strong atropine-resistant contraction of human bronchi in vitro. a rapid tachyphylaxis developed for the response to capsaicin. Both substance P and capsaicin were less potent than acetylcholine and histamine in inducing contractions of human bronchi. This finding may however be partly due to the experimental conditions and both substance P and capsaicin were comparatively much more potent in guinea-pig preparations. Transmural field stimulation of the bronchial preparations in man resulted in contractions that were largely sensitive to atropine. The presence of capsaicin-induced bronchial contractions however indicates the existence of a local non-cholinergic axon-reflex control of bronchial smooth muscle tone by substance P in man.

Intracerebral grafting of neuronal cell suspensions. IV. Behavioural recovery in rats with unilateral 6-OHDA lesions following implantation of nigral cell suspensions in different forebrain sites.

Abstract: Single and multiple implants of nigral cell suspensions were grafted to the forebrains of rats with unilateral 6-hydroxydopamine-induced dopamine denervations. Control lesions alone induced a marked behavioural asymmetry, as assessed by amphetamine- and apomorphine-induced rotation, sensorimotor tests and side bias in an unbaited T-maze, and the animals were hyperactive to a low dose of apomorphine. Single suspension placements into different denervated striatal regions were capable of reversing the behavioural asymmetries dependent upon the specific placement for each test. Multiple suspension grafts were capable of reversing all behavioural asymmetries, and additionally abolished the supersensitive hyperactivity to apomorphine. By contrast, single suspension grafts placed into the substantia nigra or lateral hypothalamus had no detectable effect on any functional measure. The results indicate that nigral suspension grafts can be at least as effective as solid grafts in reversing the functional deficits induced by dopamine denervation, provided that placements are selected within appropriate dopamine terminal regions of the forebrain (e.g. caudate-putamen or nucleus accumbens).

Intracerebral grafting of neuronal cell suspensions. II. Survival and growth of nigral cells implanted in different brain sites

Abstract: Dissociated dopamine-rich cell suspensions were prepared from the ventral mesencephalon of rat embryos and injected in one or several sites in striatal and non-striatal regions in the dopaminergically denervated brain of adult rats. While the grafts survived well in all sites, the dopamine fibre outgrowth was markedly different depending on whether the grafts occurred in an area normally innervated by the mesencephalic dopamine neurones (i.e. neostriatum or nc. accumbens) or in areas not normally innervated by these neurones (i.e. parietal cortex, lateral hypothalamus or substantia nigra). Moreover, in grafts placed at different sites along the trajectory of the nigrostriatal pathway the outgrowing fibres remained confined to the graft, and there was little evidence that the implanted neurones could elongate their axons along the pathway of the nigrostriatal tract to reach the striatum from a distance. Thus, the intracerebral suspension grafts provided efficient reinnervation of a denervated target only when placed in the immediate vicinity of the target area. The results of multiple graft placements indicate that a relatively complete restoration of a lost innervation should be possible to achieve in large areas of the brain, such as the striatal complex, with the suspension grafting technique.

Gangliosides increase the survival of lesioned nigral dopamine neurons and favour the recovery of dopaminergic synaptic function in striatum of rats by collateral sprouting.

Abstract: The effects of chronic ganglioside treatment GM-1 (10 mg/kg, i. p., once daily for 56 days) have been evaluated on the degenerative and regenerative features of nigrostriatal dopamine (DA) neurons following a partial lesion by tyrosine hydroxylase immunocytochemistry in combination with morphometrical analysis and by quantitative DA receptor autoradiography. Chronic GM-1 treatment resulted in the maintenance in the number of DA cell bodies, terminals and striatal area on the lesioned side and also increased dendrite length of the DA nerve cells in the zona reticulata on that side. The lesion induced DA receptor supersensitivity was counteracted by chronic treatment with GM-1 and the apomorphine induced rotational behaviour was significantly reduced. The hypothesis is introduced that following ganglioside treatment some lesioned DA nerve cells do not degenerate, but elongate their dendrites to give increased trophic support to DA cell bodies with intact DA axons. These increased dendro-dendritic interactions may enable the unlesioned DA cells to increase the density of their striatal nerve terminal networks via collateral sprouting leading to recovery of dopaminergic synaptic function as evidenced in the receptor autoradiographical and behavioural analysis. Gangliosides may therefore possibly represent a new type of drug in the treatment of Parkinson's disease and aging processes in DA systems.

Activity of intrastriatal nigral suspension implants as assessed by measurements of dopamine synthesis and metabolism

Abstract: The activity of intrastriatal grafts of nigral cell suspensions has been monitored biochemically, using radioenzymatic assays of dopamine, its major acidic metabolite, DOPAC, and DOPA accumulation after DOPA-decarboxylase inhibition. Implants of 4-9 microliter of nigral cell suspension restored striatal DA levels by an average of 13-18%, with the highest individual values reaching about 50% of control. DOPAC was restored from about 5% in the lesioned controls to about 20% of normal in the grafted animals. The DOPAC: DA ratios and the DOPA accumulation measures indicated that the grafted DA neurons were spontaneously active and that the transmitter turnover rate was on the average some 50-100% higher than the intact intrinsic nigrostriatal DA neurones. These results thus provide evidence that the intrastriatal nigral suspension grafts are capable of restoring dopaminergic neurotransmission in the previously denervated striatum.

Intracerebral grafting of neuronal cell suspensions. III. Activity of intrastriatal nigral suspension implants as assessed by measurements of dopamine synthesis and metabolism

Abstract: The activity of intrastriatal grafts of nigral cell suspensions has been monitored biochemically, using radioenzymatic assays of dopamine, its major acidic metabolite, DOPAC, and DOPA accumulation after DOPA-decarboxylase inhibition. Implants of 4-9 microliter of nigral cell suspension restored striatal DA levels by an average of 13-18%, with the highest individual values reaching about 50% of control. DOPAC was restored from about 5% in the lesioned controls to about 20% of normal in the grafted animals. The DOPAC: DA ratios and the DOPA accumulation measures indicated that the grafted DA neurons were spontaneously active and that the transmitter turnover rate was on the average some 50-100% higher than the intact intrinsic nigrostriatal DA neurones. These results thus provide evidence that the intrastriatal nigral suspension grafts are capable of restoring dopaminergic neurotransmission in the previously denervated striatum.

Acute effects of acetazolamide on cerebral blood flow in man.

Abstract: We have followed the time course of the effect of the carbonic anhydrase inhibitor acetazolamide injected i.v. in unanesthetized healthy human beings. The dose administered was 500 mg as a bolus. Cerebral blood flow (CBF) was measured continuously before, during and after the injection, using a pulsed ultrasound doppler system, which measured the instantaneous mean velocity across the lumen of the internal carotid artery, just below its entrance into the skull. Ventilation, heart-rate, end-expiratory PC02, arterial PC02, pH and systemic blood pressure was also measured. We found that acetazolamide caused a rise in CBF which could be detected as early as 2 min after the injection. A maximal average response of 75 % increase in CBF was seen after 25 min. The half-time of the declining phase of the response was 95 min. There were no systematic differences in the COz reactivities, given as ACBF/APAC02 in % of CBF at normocapnia, before and after acetazolamide injection, regardless of the absolute PAC02 level. The present dose of the drug caused no change in ventilation, alveolar and arterial PC02 or in arterial blood pH indicating that the carbonic anhydrase was not fully inhibited. Our observations show that acetazolamide nevertheless caused a rapid vasodilation in the brain and over a wide range of PC02’s. We suggest that this agent has a local vasodilator effect on the cerebral arterioles, unrelated to its specific effects as a carbonic anhydrase inhibitor.

Intracerebral grafting of neuronal cell suspensions. V. Behavioural recovery in rats with bilateral 6-OHDA lesions following implantation of nigral cell suspensions.

Abstract: Bilateral 6-hydroxydopamine-induced lesions of the ascending forebrain dopamine neurones induce a behavioural syndrome in rats which includes profound aphagia, adipsia, akinesia and bilateral sensorimotor neglect Such animals will die unless maintained by intragastric feeding Three experiments are reported in which we have attempted to ameliorate this syndrome with single or multiple placements of nigral cell suspensions into the forebrains of rats with bilateral dopamine depletions Although the grafts were efficient in reversing the sensorimotor and akinetic impairments, and produced a significant increase in eating, the grafted rats remained hypophagic and adipsic The results indicate that although many components of the bilateral dopamine denervation syndrome can be reversed by intrastriatal nigral suspension grafts, the severe eating and drinking deficits remain unameliorated

Projected and receptive fields: a comparison of projected areas of sensations evoked by intraneural stimulation of mechanoreceptive units, and their innervation territories.

Abstract: Microneurography and intraneural microstimulation were employed in awake human subjects to study the characteristics of cutaneous mechanoreceptive units and the sensations mediated by them. 172 units innervating the hand and forearm were identified as either PC, RA (FA in hairy skin), SA I or SA II. Analysis of action potential waveforms in a sample of units suggests that most recordings were from within the myelin sheath. Receptive fields of RA and SA I units were significantly smaller than those of PC and SA II units and showed a proximodistal size gradient, which the latter two did not. The quality of sensations evoked by intraneural stimulation was determined by the type of unit activated, except in the case of SA II units, and their magnitude could be influenced by mechanical coactivation of other sensory units. As a rule projected fields of evoked sensations were larger the further away they were from the limb tip. This grading indicates that inputs from single mechanoreceptive units are processed differently according to their source and sensory submodality, possibly as a result of unequal "resolving powers" of the corresponding cortical neurons.

Diastolic properties of the hypertrophied left ventricle in spontaneously hypertensive rats.

Abstract: The influence of myocardial hypertrophy on left ventricular volume compliance was studied in vitro in isolated hearts of 4 and 19 month old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). In both SHR groups diastolic volume compliance was similar to that in the controls, despite the presence of left ventricular hypertrophy. This seems to be mainly due to an altered geometric situation, since with increased wall thickness to internal radius ratio (w/ri), which was at hand, the less are outer myocardial layers stretched at a given increase in ventricular volume. This may imply that these layers will only little interfere with luminal distension (and thereby with diastolic volume compliance) in SHR. It was also observed that the progressive increase of ventricular hypertrophy from 4 to 19 months of age did not further increase w/ri in SHR, indicating an increase in overall ventricular size with age. Left ventricular end diastolic pressure (LVEDP) was also measured in conscious 5 week and 4 month old SHR compared with matched controls. LVEDP increased with the development of hypertension and was significantly elevated in 4 month old SHR. This will increase also the average diastolic pre-stretch of the SHR left ventricle and mobilize the "Starling mechanism" to maintain a normal stroke volume against the increased afterload for the heart in established hypertension. This seems particularly important since the hypertrophic w/ri increase (about 20%) is smaller than the great elevation of mean arterial pressure (40-50%) in SHR.

Endurance training reduces the susceptibility of mouse skeletal muscle to lipid peroxidation in vitro.

Abstract: Selected estimates of the lipid peroxidative capacity were assayed in the red and white skeletal muscles of control and endurance-trained mice. Endurance training decreased the lipid peroxidation rate in vitro in both muscle types. The concentration of lipids susceptible to Fe2+-induced lipid peroxidation was greater in the red than in the white skeletal muscle and increased after endurance training in the red muscle. Endurance training, however, decreased highly significantly the sensitivity of red muscle to in vitro stimulated lipid peroxidation. The activity of catalase and the concentration of vitamin E were considerably higher in the red muscle, whereas the activity of glutathione peroxidase was slightly higher in the white muscle. Endurance training caused no changes in these antioxidants. Endurance training increased the concentrations of reduced and total non-protein glutathione in the red skeletal muscle but not in the white muscle. The total sulfhydryl group contents were unaffected. Our results suggest that endurance training may increase the resistance of skeletal muscle to injuries caused by lipid peroxidation.

The involvement of intramural nerves in cholera toxin induced intestinal secretion.

Abstract: In previous reports we have suggested that nervous reflexes are involved in the pathophysiology of cholera secretion and that these nervous reflexes involve a cholinergic synapse and a neuron with vasoactive intestinal polypeptide (VIP) as neurotransmitter. These proposals were further analyzed in this study. Tetrodotoxin (TTX) and lidocaine applied on the serosal surface inhibited cholera secretion in segments of rat small intestine. Fluid absorption in control rats was not significantly changed. Hexamethonium given i.v. decreased cholera secretion in the cat. No additional inhibition of cholera secretion was observed after giving TTX close i.a. Furthermore, the intestinal secretion evoked by VIP was not influenced by hexamethonium given i.v. or TTX given close i.a. The present observations support the hypothesis of a role for nervous reflexes in cholera secretion. The results suggest that at least a major part of the proposed nervous reflex(es) in cholera have a cholinergic synapse. Furthermore, the VIP-ergic neuron is situated "distal" to the cholinergic neuron in the reflex(es) closer to the effector cells.

Changes in segmental reflexes following chronic spinal cord hemisection in the cat. I. Increased monosynaptic and polysynaptic ventral root discharges.

Abstract: The effect of a chronic spinal cord hemisection on segmental reflex transmission was studied in cats. Recordings of ventral root responses were made after a terminal transection below the initial lesion to eliminate descending influence through the intact spinal half. Procedures to ensure comparability between sides, that are lacking in earlier work on this experimental model, were introduced in the present work. It was demonstrated that there was an increase in reflex size on the lesioned (left) side, relative to the other side, of both mono- and polysynaptic reflexes. The reflex changes were found at all survival times studied (from 2 to 515 days). In control animals mono- and polysynaptic reflexes were found to be larger on the right side. It is discussed that side symmetry of reflex size is not to be presupposed even in a normal population. Detailed clinical examinations of lesioned animals were not performed, but a tendency for enhancement of the ipsilateral knee-jerk was found. There was no syndrome of spasticity and general motor recovery was very good.

Morphology, distribution, and specificity of olfactory receptor cells in salmonid fishes.

Abstract: Electrophysiological and anatomical investigations of the olfactory epithelium of three salmonid species have been coordinated. Different corridors in the olfactory rosettes were examined by recording of the electro-olfactogram (EOG) using two recording electrodes simultaneously against one common indifferent electrode. Biopsies comprising the two lamellae bounding each of the examined corridors were examined by scanning electron microscopy (SEM). The electrophysiological results confirm a higher relative density of bile salt-receptors in the peripheral parts of all the corridors, and a higher relative density of amino acid-receptors in central parts. The SEM micrographs show that ciliated receptor cells are more numerous than microvillous ones. The density of ciliated receptor cells increases towards the peripheral margin of each lamella. The density of microvillous receptor cells increases towards the central margin. The correspondence between the electrophysiological and the anatomical observations support the hypothesis that the ciliated receptor cells are those specific to bile salt-like substances, the microvillous those specific to amino acids.

Comparison of urinary and plasma catecholamine responses to mental stress.

Abstract: 8 subjects were exposed to the Stroop mental performance test in a design with alternating hourly periods of rest and stress. During each period one urine sample and several venous plasma samples were obtained. Heart rate responded rapidly to initiation and termination of the stress exposure with increases and decreases respectively. Both urinary and plasma adrenaline increased significantly during stress. The plasma response was immediate and sustained. Neither urinary, nor plasma noradrenaline were significantly increased by the test. Plasma noradrenaline, however, increased significantly on termination of the exposure to stress. It was suggested that the latter effect may be due to muscle sympathetic nerve activity decreasing during stress and increasing following stress. The sample-to-sample variation was more than 20% of the mean for both catecholamines, indicating the need for frequent sampling to reliably reflect plasma levels. The mean intraindividual plasma/urine correlation was r = 0.70 (p less than 0.001) for adrenaline and r = 0.40 (p less than 0.05) for noradrenaline. When only resting periods were considered, no significant correlations remained, apparently due to a reduced range of variation and accompanying reduced signal-to-noise ratio. It is concluded that both urinary and plasma adrenaline may be useful in the evaluation of changes in sympatho-adrenal activity during stress.

An oscillating intratubular pressure response to alterations in Henle loop flow in the rat kidney

Abstract: We describe in gas anesthetized rats an oscillating intratubular pressure response, probably of vascular origin, sensitive to small physiological changes in fluid delivery to the distal tubule. The oscillation appararently indicates that an adjustment of vascular resistance is in operation, but at present it reveals neither the effector site (afferent and/or efferent arteriole) nor the effector mechanism (vasoconstriction and/or dilatation). The renin-angiotensin system seems to be involved in this phenomenon.

The regulation of glycogen phosphorylase and glycogen breakdown in human skeletal muscle.

Abstract: The regulation of glycogen phosphorylase and glycogen breakdown in human skeletal muscle has been investigated using the needle biopsy technique. Preliminary studies showed that the activity of phosphorylase in vitro was dependent upon the concentration of inorganic phosphate (Pi) used in the assay system. The Km of phosphorylase a for Pi was found to be 26.2 mmol/l, and that of (a+b) (assayed in the presence of saturating AMP) was 6.8 mmol/l. Because of the difference in Km the apparent percentage of a to (a+b) activity varies with the Pi concentration used in the assay system. Phosphorylase a and (a+b) activities were therefore adjusted to saturating Pi concentrations. The ratio of the activities in this case is independent of the Pi concentration and constitutes a minimal estimate of the fraction of phosphorylase molecules in the a form. The fraction of phosphorylase in the a form in resting muscle was as a mean 22%. Despite nearly a quarter of the phosphorylase being in the a form glycogenolytic activity is extremely low. It is proposed that the concentration of Pi at the active site of the enzyme is low compared to the Km for this of either form of the enzyme, and is limiting to activity. A Pi concentration in resting muscle of 1-3 mmol/l was calculated. During epinephrine infusion at rest 90% of the phosphorylase was transformed to the a form but only a moderate increase in the glycogenolytic rate occurred. This rate approximated to 5-10% of the maximum rate of the enzyme (Vmaxa). During prolonged epinephrine infusion the glycogenolytic rate decreased despite the continuance of 90% or more of the phosphorylase in the a form. In contrast to epinephrine infusion prolonged ischemia resulted in a decrease in the mole fraction of phosphorylase a and simultaneously in an increase of the glycogenolytic rate. During isometric and dynamic exercise there was a rapid transformation of phosphorylase b to a paralleled by pronounced increase in the rate of glycogen breakdown. The increased rate of glycogenolysis during isometric exercise was close to the Vmax of phosphorylase a in vivo. When either form of exercise was continued to fatigue/exhaustion, a re-transformation of phosphorylase a to b was observed. During dynamic exercise cAMP in the muscle increased two fold. This increase was blocked by the prior administration of propranolol.+