Assessment of the effectiveness of -adrenoceptor blocking agents towards cardiac and bronchiolar responses of the pithed guinea-pig to electrical stimulation of the spinal outflow.
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1. The responses of heart rate and resistance to lung inflation of the pithed guinea-pig on electrical stimulation of the thoracic spinal roots could be related to similar responses to injected catecholamines, such that dose-stimulus frequency relations could be plotted.2. The range of frequency of stimulation that was equi-effective with a dose range of injected catecholamines was higher for effects on air overflow than for heart rate. The slope of the relations for heart rate also differed from that for air overflow. These features may reflect a difference in effectiveness of the sympathetic innervation of heart and bronchial tree.3. Propranolol was equally effective in reducing the responses of heart rate and air overflow to injected noradrenaline. Practolol was somewhat more active against the effects of noradrenaline on air overflow than on heart rate, though equally active against the effects of isoprenaline.4. For the assessment of equivalent blockade of the effects of cord stimulation on heart rate and air overflow, frequency-ratios corresponding to a noradrenaline dose-ratio of 2 were derived from the slopes of the dose-frequency relations; for air overflow this value was approximately 2 and for heart rate approximately 1.4.5. When the doses required to produce these degrees of blockade were computed from the dose-response relations for blockade of the effects of cord stimulation by propranolol, they were found to be similar for effects on heart rate and air overflow. For practolol, the effective dose for block of heart rate increase was found to be lower than that for air overflow. (+info)
Depressor responses to spinal stimulation in the pithed rat.
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1. Electrical stimulation of the spinal nerves in the pithed rat preparation produces a pressor response due to sympathetic vasoconstriction.2. When the vasoconstrictor effect of sympathetic stimulation is abolished by guanethidine or hexamethonium and the blood pressure is raised by noradrenaline infusion, spinal stimulation produces depressor responses or complex responses containing depressor components.3. Contractions of skeletal muscle caused by stimulation of motor nerves result in complex changes in blood pressure consisting of a pressor component due to clamping of muscle blood vessels and a secondary depressor phase due to functional hyperaemia.4. The depressor response is partly due to stimulation of cholinergic postganglionic fibres. The acetylcholine released, which causes vasodilatation, may be the overflow from neuromuscular junctions or ganglionic synapses.5. Stimulation of the nerves to the adrenal medulla causes release of adrenaline which has a vasodilator effect during noradrenaline infusion. (+info)
The effects of peripheral and central nervous influences on gastric centre neuronal activity in sheep.
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1. Responses of identified vagal reticulo-ruminal motoneurones and gastric centre interneurones to changes in vagal afferent activity were examined in anaesthetized, decerebellate sheep.2. Procedures which reflexly modified the form of forestomach movements caused corresponding changes in the activities of motoneurones and Type A interneurones, whereas the activity patterns of Type B, and many Type C, interneurones were not affected.3. Distension of the pyloric region of the abomasum reduced the number of spikes in the periodic discharges of gastric centre neurones (motoneurones and Type A interneurones) with reticular activity, although the frequency of periods of activity was often increased. The afferent pathway for both effects was probably vagal.4. Unilateral vagotomy usually had little effect on the frequency and amplitude of forestomach movements, and did not influence the temporal relation between ipsilateral gastric centre discharges and the movements.5. Median division of the medulla oblongata only in the region between the gastric centres caused a loss of synchronization in the activities of the two centres, indicating the existence of commissural connexions at this level.6. Bilateral vagotomy abolished forestomach movements and motoneuronal activity, but rhythmic activity in gastric centre interneurones continued with a periodicity of approximately 1 min. This persisting periodic activity was unaffected by spinal section, but was not present after transection of the brain stem rostral to the medulla.7. Cyclical gastric centre activity could be elicited by reticular distension in preparations in which the medulla oblongata was isolated from higher regions of the brain, but, in contrast to many sheep in which the brain stem was intact, the existence of the activity was totally dependent upon peripheral afferent activity.8. The evidence indicates that medullary neurones responsible for periodic activation of vagal preganglionic reticulo-ruminal motoneurones may be excited by either or by both vagal afferent fibres from the fore-stomach or by descending, as yet unidentified, influences from the central nervous system.9. Possible roles for gastric centre interneurones in neural networks which control the periodic activation of motoneurones and which control the form of individual activity cycles are discussed. (+info)
A sympathetic reflex elicited by distension of the mesenteric venous bed.
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1. The proximal ends of the distal portions of severed nerves coming from the small intestine were monitored for nerve impulses. When the mesenteric venous pressure was increased by mechanical obstruction of the portal vein there was a proportional increase in the frequency of afferent action potentials, the frequency falling immediately the venous pressure was reduced. The stimulus for the increased rate of nerve discharge appeared to be pressure within the mesenteric venous bed and not anoxia, for obstruction of the arterial supply to the gastrointestinal tract did not activate the same fibres.2. Obstruction of the portal vein led to an increased efferent nervous discharge to the intestines. The reflex increase persisted after bilateral vagotomy, after transection of the spinal cord at the level of C7 and after section of the hepatic nerves, but was abolished by section of the intestinal nerves.3. It is suggested that the spinal reflex is concerned with local distribution of blood and that the mesenteric venous ;volume' or ;stretch' receptors which initiate the reflex are similar to those described elsewhere in the body. (+info)
Reflex firing in the lumbar sympathetic outflow to activation of vesical afferent fibres.
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1. Activation of vesical afferent fibres in the Agammadelta range by electrical stimulation of the pelvic nerve or by bladder distension elicited reflex firing in hypogastric nerves and in preganglionic nerves to the inferior mesenteric ganglion.2. The multisynaptic reflex was present in cats with an intact spinal cord and in acute and chronic spinal animals (transections at T10-T12). The reflex pathway was partially crossed in the sacral cord, and in the periphery at the level of the inferior mesenteric ganglia. In contrast, an inhibitory response to raised intravesical pressure was mediated by a supraspinal inhibitory mechanism which was activated in parallel with the micturition reflex.3. Since enhancement as well as depression of sympathetic firing accompanied reflex micturition, it is concluded that at least two distinct populations of lumbar preganglionic neurones are responsive to vesical afferent activity: one population being excited, the other depressed, during micturition. The latter population may be involved in an inhibitory feed-back mechanism on to the bladder. (+info)
An experimental analysis of the tachycardia that follows vagal stimulation.
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1. Postvagal tachycardia, the transient increase in heart rate that follows the sinus bradycardia elicited by vagal stimulation, was investigated in thirty chloralosed cats. Maximum postvagal tachycardia was elicited by stimulation at frequencies of 20-60 Hz with train durations of 30-90 sec. A positive correlation was demonstrated between the magnitudes of postvagal tachycardia and of the preceding sinus bradycardia.2. Postvagal tachycardia was not affected by either spinal transection at C7 or by administration of propranolol (1.5 mg/kg I.V.), but was abolished by the administration of atropine (2.0 mg/kg I.V.).3. Postvagal tachycardia was observed to follow the vagal bradycardia induced reflexly either by administration of phenyldiguanide (100-300 mug I.V.) or by stimulation of the aortic depressor nerve.4. In the isolated atria-vagus preparations from six rabbits a positive correlation was demonstrated between the magnitude of postvagal tachycardia and of the preceding bradycardia elicited by vagal stimulation.5. Continuous intracellular recordings were obtained from four sinuatrial node pace-maker cells in the isolated atria-vagus preparation of the rabbit before, during and after vagal stimulation. During postvagal tachycardia the slope of the diastolic prepotential, the maximum diastolic potential, threshold potential and the overshoot were found to be increased; these changes are different from those found in pace-maker cells during adrenergic activation.6. These findings demonstrate that postvagal tachycardia is not mediated by sympathetic adrenergic mechanisms, but suggest that it is dependent upon the preceding vagal bradycardia and may be related to an increase in net sodium influx into pace-maker cells initiated by the hyperpolarization of the pace-maker cell membrane during and immediately after vagal stimulation. (+info)
Peripheral cardiovascular effects, in the pithed rat, of compounds used in the treatment of hypertension.
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A method for stimulating discrete segments of the spinal autonomic outflow in the pithed rat was found suitable for differentiating between the group of centrally acting antihypertensive agents alpha-methyldopa, clonidine and iproniazid and other antihypertensive compounds which additionally have peripheral vascular effects mediated via the peripheral sympathetic nerves. (+info)
A technique for the study of muscle relaxants by stimulating the spinal motor nerve outflow in the pithed rat.
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The motor nerve outflow in the pithed rat was stimulated from the spinal column and contractions of individual skeletal muscles recorded. The preparation is anaesthetic-free and well suited to a study of muscle relaxants. (+info)