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PubMed1990

Effects of endothelin on arterial pressure and venous tone in intact and hexamethonium-treated conscious rats.

The dose-response effects of the potent vasoconstrictor peptide endothelin on mean arterial pressure (MAP), heart rate (HR), and mean circulatory filling pressure (MCFP), an index of body venous tone, were investigated in conscious and unrestrained, intact rats as well as in rats continuously infused with the ganglionic blocker hexamethonium. The dose of hexamethonium selected was that which reduced the reflex tachycardia induced by i.v. injections of acetylcholine by 50%. In intact rats and rats pretreated with hexamethonium, i.v. injections of endothelin caused dose-dependent increases in MAP and decreases in HR. Low doses of endothelin did not affect MCFP while the highest dose in the intact rat, and the two highest doses in hexamethonium-treated rats, caused small but significant increases in MCFP. Our results suggest that endothelin has small effects on body venous tone in contrast to its effectiveness in raising arterial pressure.

Animals↗
PubMed1997

Hemodynamic responses to endothelin-1 and endothelin antagonists microinjected into the nucleus tractus solitarius in rats.

The role of endothelin-1 (ET-1) within the nucleus tractus solitarius (NTS) in central cardiovascular control was investigated by local microinjections of ET-1 and ET-receptor antagonists. In urethane-anesthetized Sprague-Dawley rats, a unilateral microinjection of ET-1 (1.0, 3.3, and 10.0 pmol) into the NTS significantly increased arterial pressure, left ventricular systolic pressure, and dP/dt(max) in a dose-dependent manner, and slightly decreased heart rate in a dose-independent manner. The pressor effect lasted >90 min. In normotensive rats, neither PD147953, a selective ETA-receptor antagonist, nor PD142893, a mixed ETA- and ETB-receptor antagonist, microinjected into the NTS elicited any changes in arterial pressure or heart rate. The pressor and bradycardic effects evoked by microinjection of ET-1 into the NTS could be blocked by local pretreatment with PD147953 and completely eliminated by intravenous pretreatment with the ganglionic blocker hexamethonium. The arterial baroreflex sensitivity was almost totally suppressed by microinjection of ET-1 (3.3 pmol) in alpha-chloralose-anesthetized Sprague-Dawley rats. A similar pattern of changes in the hemodynamic variables was elicited by microinjection of ET-1 (3.3 pmol) into the NTS in spontaneously hypertensive rats (SHRs) compared with Wistar-Kyoto (WKY) rats. In SHRs, microinjection of PD142893 did not elicit any changes in arterial pressure or heart rate. These results suggest that ET-1 modulates reflex control of hemodynamics by activation of autonomic nerve via ETA receptors in the NTS, and that the responsiveness of SHRs to ET-1 or PD142893 is similar to that of WKY rats.

Animals↗
PubMed2000

Sympathoinhibitory and depressor responses to long-term infusion of nifedipine in spontaneously hypertensive rats on high-salt diet.

Short-term (by hour) intracerebroventricular (i.c.v.) or i.v. infusion of nifedipine at low rates evokes parallel decreases in renal sympathetic nerve activity (RSNA) and blood pressure (BP) in spontaneously hypertensive rats (SHR). In the present study, effects of long-term administration of nifedipine on BP and control of sympathetic tone were examined in SHR on a high-salt (8%) diet. From 6 to 8 weeks of age, for 2 weeks concomitant with taking a high-salt diet, rats were also treated with subcutaneous infusion of nifedipine at 10, 50, or 100 microg/kg/h or vehicle solvent as control using osmotic minipumps. At the end of the 2-week treatment period, mean arterial pressure (MAP), heart rate (HR), and RSNA at rest and in response to air-jet stress, i.c.v. injection of the alpha-adrenoceptor agonist guanabenz (25 microg), and i.v. injection of the ganglionic blocker hexamethonium were recorded in conscious rats. In rats on nifedipine 50 or 100 microg/kg/h, resting MAP was significantly lower (136+/-4 or 130+/-4 vs. 145+/-2 mm Hg in control rats, p < 0.05 for both), the sympathoinhibitory and depressor responses to i.c.v. guanabenz were significantly decreased, and the absolute decreases in MAP in response to i.v. injection of hexamethonium were significantly smaller. Sympathoexcitatory and pressor responses to air-jet stress, however, were not affected by nifedipine. Infusion of nifedipine at the three rates for 2 weeks caused concentrations of plasma nifedipine in a dose-related manner. Nifedipine was not detected in tissues of rats treated with 10 microg/kg/h nifedipine but was present in brain and other tissues of rats treated with nifedipine at the two higher rates. Thus in SHR on high-salt intake long-term treatment with nifedipine at 50 or 100 microg/kg/h decreased resting BP and the sympathetic component in BP control. In addition to possible peripheral effects, long-term administration of nifedipine may also act centrally to decrease sympathetic activity and BP, likely by increasing activity in central pathways involving sympathoinhibition, but not in pathways involving sympathoexcitation as evaluated by air-stress.

Animals↗
PubMed1989

The use of continuous spinal anesthesia in severe tetanus with autonomic disturbance.

Eight patients with severe tetanus experienced episodes of marked cardiovascular instability. During these unstable periods, cardiac output and vascular resistance varied independently. Beta blocking and low doses of ganglionic blocking agents failed to control cardiovascular instability even when combined. High doses of ganglionic blockers stabilized hemodynamics for a short period, but caused the elevation of transaminases. After unsuccessful treatment with cardiovascular drugs, continuous spinal anesthesia (CSA) was applied to five patients. For 5 to 23 days circulation was regulated artificially under complete blockade of the autonomic nervous system by infusing isotonic 0.5% bupivacaine intrathecally. Catecholamine was added intravenously to maintain adequate blood pressure. Before the introduction of CSA, three patients died of circulatory failure. In contrast, CSA dramatically suppressed the cardiovascular instabilities, and all five treated patients survived. This suggests that both sympathetic and parasympathetic nervous systems need to be blocked to stabilize hemodynamics in severe tetanus.

Adult↗
PubMed1991

Hemodynamic response with passive neck flexion in brain death.

Twelve brain-dead patients admitted to the Department of Traumatology, Osaka University Hospital, from July 1988 to August 1989 were studied. A hemodynamic response elicited by passive neck flexion was observed in 10 of the 12 patients. After passive neck flexion, blood pressure began to rise, and the heart rate increased slightly. Blood pressure peaked about 2 minutes after the initiation of neck flexion and then decreased gradually to the baseline level within a few minutes. These responses were suppressed completely by administration of the ganglion blocker trimethaphan camsilate, which suggests that the efferent pathway of the response is mediated by the sympathetic nervous system.

Adolescent↗
PubMed2005

Neuronal nitric oxide synthase and splanchnic blood flow in anaesthetized rats.

AIMS: To evaluate to what extent the neuronal form of constitutive nitric oxide synthase (nNOS) contributes to the blood perfusion of splanchnic organs, including the islets of Langerhans. METHODS: The nNOS inhibitor 7-nitroindazole (300 mg kg(-1) i.p.) was administered to anaesthetized Sprague-Dawley rats, some of which were pre-treated with the ganglionic blocker hexamethonium (20 mg kg(-1) i.v.) The blood perfusion of the splanchnic organs, including the pancreatic islets was then measured with a microsphere technique. RESULTS: Nitroindazole decreased total pancreatic, duodenal and renal blood flow, whereas pancreatic islet, colonic and adrenal blood flows were unchanged. A slight increase in mean arterial blood pressure was seen after nitroindazole treatment. Nitroindazole did not affect blood glucose or serum insulin concentrations. In separate experiments, hexamethonium affected none of the studied blood flow values, suggesting that the effects of nNOS-inhibition were not mediated from the nervous system. CONCLUSION: Nitric oxide derived from the activity of nNOS contributes to the blood perfusion in the upper portions of the gastrointestinal tract, viz. the parts supplied by the cranial mesenteric artery, and the kidneys, whilst no effects are seen on colonic or adrenal blood flow. Pancreatic islet blood flow was unaffected by nNOS inhibition, thereby suggesting that NO derived from the other isoforms of NOS maintains the high basal islet blood perfusion.

Anesthesia, General↗
PubMedDate not supplied

Cardiovascular effects of tubocurarine in man.

The cardiovascular effects of tubocurarine in patients anaesthetised with thiopentone or ketamine have been compared, using volume-pulse finger plethysmography, electrocardiography, sphygmomanometry and impedance cardiography for the clinical assessments. Tubocurarine potentiates the arterial hypotensive effect of thiopentone and reverses the hypertensive action of ketamine. It also prevents the dysrhythmic (adrenergic) reaction of the heart to orotracheal intubation and has less effect on the positive chronotropic and inotropic reactions thereto. Hypotensive doses of tubocurarine in patients anaesthetised with thiopentone do not prevent reflex constriction of the finger blood vessels in response to surgical stimuli (orotracheal intubation) which means that the drug is not a sympathetic ganglion blocker in man. It is concluded that tubocurarine is a myocardial depressant which acts, like verapamil, as a calcium ion antagonist.

Adult↗
PubMed1983

Dose-response relationships of intravenous hyoscine butylbromide and atropine sulphate on heart rate in healthy volunteers.

Heart-rate responses to intravenous hyoscine butylbromide, atropine and physiological saline in cumulative dosage regimens have been recorded in six healthy subjects. Atropine sulphate induced bradycardia at low, and tachycardia at higher, dose levels whereas hyoscine butylbromide caused only tachycardia but with a flatter dose-response relationship. Exact potency ratios could not be calculated because of the differing dose-response curves. However, an approximate estimate from a comparison of equiactive doses at the upper part of the curve yielded a value less than one half that obtained from the drugs' affinity constants in guinea-pig ileum. The findings suggest that, in addition to its action as a muscarinic antagonist, hyoscine butylbromide is a ganglion blocker in man as it is in animals.

Adult↗
PubMed1983

Effect of diazoxide-induced hypotension on cerebral blood flow in hypertensive rats.

The effect on cerebral blood flow of acute diazoxide-induced hypotension was studied in rats with renal and spontaneous hypertension. Diazoxide (5 mg/kg, i.v. bolus), caused arterial pressure to fall rapidly to that of normotensive rats, i.e. c. 75 mmHg. There was a concomitant fall in cerebral blood flow of about 35% (P less than 0.01) in renal hypertensive rats and 25% (P less than 0.05) in spontaneously hypertensive rats; the greater fall in flow in the former corresponded to a greater drop in pressure. Flow remained at these reduced levels during a 2 h observation period. Histological examination revealed small areas of ischaemic damage in the brains of five of the twelve animals. In control hypertensive rats not given diazoxide, cerebral blood flow and blood pressure were stable during a 2 1/2 h period and there was no evidence of ischaemic damage to the brains. The diazoxide-induced reduction in cerebral blood flow was interpreted as being secondary to a blood pressure fall to below the lower limit of cerebral blood flow autoregulation. No evidence was found of direct effects on the cerebral circulation such as seen with ganglionic blockers, alpha-blockers and cerebral vasodilators.

Animals↗
PubMed1982

Anaesthesia and cardiovascular regulation.

Cardiovascular homeostasis is dependent on the efficient performance of the effector organs, i.e. the vascular smooth muscle and the heart. Besides inherent activity and local control mechanisms, these effector organs are regulated by circulatory control centres within the central nervous system, which in turn receives information from receptors inside and outside the cardiovascular system. All these components of the circulatory systems, i.e. receptors, afferent and efferent pathways, control centres and effector organs, are possible sites for interactions by anaesthetics. Since different anaesthetics have different potencies and special predilections, there are a large variety of interaction patterns, as is discussed in the paper. Another way of evaluating circulatory effects of drugs used in anaesthesia is to analyse how these drugs may modify circulatory reflexes associated with surgery and trauma. For example, pain, hypoxia and/or hypovolaemia may evoke circulatory adjustments which correspond to and are functionally related to, from experimental physiology, well-known reflex patterns such as the somatosympathetic reflex, the chemoreceptor reflex and the baroreceptor reflex. These reflex adjustments are liable to modification by anaesthetics, as exemplified in the paper. Due to the complexity of circulatory control and the varying effects of different anaesthetic agents, it is difficult to draw general conclusions. It can, however, be stated that most general anaesthetics depress cardiovascular reflexes in proportion to the depth of anaesthesia, and that suprabulbar centres are more easily depressed than bulbar ones. Opiates seem to have a specific inhibitory effect on circulatory adjustments induced by noxious stimuli. Transmission in efferent and afferent pathways is liable to modification by local anaesthetics, ganglionic blockers or alpha- and beta-receptor antagonists.

Anesthesia↗
PubMed1988

Suppression of the pressor effect of centrally administered thyrotropin-releasing hormone under halothane, pentobarbital and flunitrazepam anaesthesia.

Intracerebroventricular (i.c.v.) administration of thyrotropin-releasing hormone (TRH) caused an increase in blood pressure (BP) and heart rate (HR) in conscious rats. The pressor effect was greatly diminished by adrenalectomy as well as after pretreatment with phentolamine, an alpha-receptor antagonist or with mecamylamine, a ganglion blocker, suggesting that centrally administered TRH increases BP mainly by stimulating sympathetic activity. Under halothane (0.8%), pentobarbital (33 mg/kg, i.p.) and flunitrazepam (0.8 mg/kg, i.v.) anaesthesia, the pressor effect of TRH was almost completely blocked. The increase in BP induced by peripheral alpha-receptor stimulation with phenylephrine was not affected by the anaesthetics at these doses. Pretreatment with atropine (50 micrograms, i.c.v.) significantly reduced the pressor effect of TRH. Intracerebroventricularly administered haloperidol and bicuculline also partially diminished the increase in BP produced by TRH, while other neurotransmitter blockers such as phentolamine, propranolol and naloxone did not. These results indicate that the anaesthetics at the doses employed interfere with the central neuronal pathway(s), probably cholinergic pathways, through which TRH exerts its pressor effect.

Animals↗
PubMed2005

Pressor and tachycardic responses evoked by microinjections of L-glutamate into the medial prefrontal cortex of unanaesthetized rats.

The ventral medial prefrontal cortex (vMPFC) is involved in central cardiovascular control. In the present study, we studied the cardiovascular effects of injections of L-glutamate into the vMPFC of unanaesthetized rats and the mechanisms of these effects. Male Wistar rats were used and L-glutamate was microinjected in the vMPFC in a final volume of 200 nL. Microinjections of L-glutamate (9, 27, 81, 150 or 300 nmol) caused long-lasting, dose-related pressor and tachycardic responses in unanaesthetized rats. No differences were observed among cardiovascular responses when L-glutamate was injected into the three sub-areas that comprise the vMPFC, namely the prelimbic, the infralimbic and the dorsal peduncular cortices. No responses were observed when the dose of 81 nmol of L-glutamate was microinjected into surrounding structures such as the cingulate cortex area 1, the corpus callosum and the tenia tecta, indicating a predominant action on the vMPFC. The cardiovascular response to L-glutamate into the vMPFC was blocked by intravenous pretreatment with the ganglion blocker pentolinium (10 mg/kg, i.v.) or the beta1-adrenoceptor antagonist atenolol (1.5 mg/kg, i.v.), supporting the involvement of the cardiac sympathetic nervous system in the response to L-glutamate. Pretreatment with the muscarinic antagonist homatropine methyl bromide (1 mg/kg, i.v.) reduced the latency to the onset of the pressor and tachycardic responses to L-glutamate injected into the vMPFC without significant effects on response duration or maximum effect. We conclude that stimulation of the vMPFC with L-glutamate caused pressor and tachycardic responses in unanaesthetized rats, responses which were dependent on cardiac sympathetic nerve activation and were potentiated by blockade of peripheral muscarinic receptors.

Animals↗
PubMed2005

Cardiovascular effects of noradrenaline microinjected into the dorsal periaqueductal gray area of unanaesthetized rats.

The periaqueductal grey area (PAG) is a mesencephalic region that is involved in the modulation of cardiovascular changes associated with behavioural responses. Among the neurotransmitters present in the PAG, noradrenaline (NA) is also known to be involved in central nervous system cardiovascular regulation. In the present study we report the cardiovascular effects of the microinjection of NA into the dorsal portion of the PAG (dPAG) of unanaesthetized rats and the peripheral mechanism involved in their mediation. Injection of NA in the dPAG of unanaesthetized rats evoked a dose-dependent pressor response accompanied by bradycardia. The magnitude of the pressor responses was higher at more rostral sites in the dPAG and decreased when NA was injected into the caudal portion of the dPAG. The responses to NA were markedly reduced in urethane-anaesthetized rats. The pressor response was potentiated by i.v. pretreatment with the ganglion blocker pentolinium and blocked by i.v. pretreatment with the vasopressin antagonist dTyr(CH2)5(Me)AVP. The results suggest that activation of noradrenergic receptors within the dPAG can evoke pressor responses, which are mediated by acute vasopressin release.

Animals↗
PubMed1991

Stress- and endotoxin-induced increases in brain tryptophan and serotonin metabolism depend on sympathetic nervous system activity.

Stressful treatments and immune challenges have been shown previously to elevate brain concentrations of tryptophan. The role of the autonomic nervous system in this neurochemical change was investigated using pharmacological treatments that inhibit autonomic effects. Pretreatment with the ganglionic blocker chlorisondamine did not alter the normal increases in catecholamine metabolites, but prevented the increase in brain tryptophan normally observed after footshock or restraint, except when the duration of the footshock period was extended to 60 min. The footshock- and restraint-related increases in 5-hydroxyindoleacetic acid (5-HIAA) were also prevented by chlorisondamine. The increases in brain tryptophan caused by intraperitoneal injection of endotoxin or interleukin-1 (IL-1) were also prevented by chlorisondamine pretreatment. The footshock-induced increases in brain tryptophan and 5-HIAA were attenuated by the beta-adrenergic antagonist propranolol but not by the alpha-adrenergic antagonist phenoxybenzamine or the muscarinic cholinergic antagonist atropine. Thus the autonomic nervous system appears to be involved in the stress-related changes in brain tryptophan, and this effect is due to the sympathetic rather than the parasympathetic limb of the system. Moreover, the main effect of the sympathetic nervous system is exerted on beta- as opposed to alpha-adrenergic receptors. We conclude that activation of the sympathetic nervous system is responsible for the stress-related increases in brain tryptophan, probably by enabling increased brain tryptophan uptake. Endotoxin and IL-1 also elevate brain tryptophan, presumably by a similar mechanism. The increase in brain tryptophan appears to be necessary to sustain the increased serotonin catabolism to 5-HIAA that occurs in stressed animals, and which may reflect increased serotonin release.

Animals↗
PubMed1990

Validation of a novel technique allowing assessment of the functional role of cardiac prejunctional receptors in the rat.

1. The electrical stimulation of the thoracic portion of the spinal cord (preganglionic nerve fibres) in the pithed rat is a widely used technique to investigate drug effects on the sympathetic nervous system. However, it does not allow discrimination between ganglionic and neuronal ending sites of action of drugs. This report describes and validates an experimental approach in which postganglionic nerve fibres are stimulated in pithed rats, thereby overcoming the above mentioned difficulty. 2. Electrical stimulation of a nerve below the thymus gland produced frequency-related increases in heart rate which were not modified by the ganglion blockers, hexamethonium or mecamylamine, but were reduced by the beta 1-adrenoceptor antagonist, betaxolol. Thus, the studied nerve fibres can be classified as sympathetic postganglionic neurons. 3. The parameters for electrical stimulation of postganglionic cardioaccelerator nerve fibres giving optimal responses were of similar pulse widths as required for the stimulation of the thoracic spinal cord, but of lower strength of current, higher frequencies and shorter stimulation times to achieve steady-state responses. 4. Clonidine reduced the tachycardia evoked by sustained electrical stimulation of postganglionic cardioaccelerator nerve fibres. This effect was antagonized entirely by the selective alpha 2-adrenoceptor antagonist, idazoxan. Therefore, sympathetic cardiac postganglionic nerve fibres are endowed with alpha 2-adrenoceptors.

Animals↗
PubMed1968

Studies on renal vasomotion.

1. The present investigation was made on the left kidney of the dog. The animals were anaesthetized intravenously with pentobarbitone (30 mg/kg) and the kidneys were perfused with saline at room temperature (20 degrees -22 degrees C). The renal innervation was untouched.2. Stimulation of the left splanchnic major nerve at T10-T12, and of the renal nerves, consistently caused renal vasoconstriction.3. Repeated stimulation of both supradiaphragmatic vagi failed to induce any vasomotion in the kidney.4. The vasoconstrictor effect was not blocked by either nicotine or hexamethonium even in enormous doses (30,000 mug). This may indicate that renal ganglia do not exist, for these ganglion blockers would prevent transmission across the ganglia.5. Kidney perfusate, re-injected into the kidney after vasoconstriction induced by stimulation of the renal nerves, brought about a notable reduction in outflow. This effect was not observed when perfusate from a non-stimulated kidney was used. This points to the release of a vasoconstrictor substance after nervous stimulation.6. Acetylcholine (ACh) in concentrations ranging from 0.001 mug/ml. caused a reduction in renal outflow. Thresholds were extremely variable. Higher concentrations of ACh (100-1,000 mug/ml.) often induced vasodilatation. The vasoconstrictor effect of ACh was not blocked by atropine.7. Nicotine and hexamethonium (10,000-30,000 mug) induced blockade which elevated the threshold for ACh to values of 1,000 mug/ml.8. Noradrenaline (0.0001 mug/ml.) induced a strong renal vasoconstriction.9. Hydergine (5-10 ml. solutions in concentrations ranging from 15 to 30 mug/ml.) blocked the renal response to nerve stimulation. This suggests that the nature of the renal innervation is adrenergic.10. In diseased kidneys which show reduction of the lumen of the arterioles, the thresholds for ACh, nicotine and noradrenaline are greatly increased, which might explain why we failed to show any effect of these drugs on renal vasomotion in several kidneys, many of which were not examined histologically.11. The collision technique was applied in an attempt to discover the nature of the fibres activated by ACh. It was found that ACh greatly reduced the size of the action potentials generated by splanchnic stimulation. This would seem to indicate that these impulses are conducted antidromically by sympathetic postganglionic fibres.12. These findings are discussed in relation to the hypothesis that the renal innervation is chiefly adrenergic and that ACh acts as a sympathetic transmitter, liberating noradrenaline, and that this effect is blocked at postganglionic endings, or at some structure intervening between adrenergic nerve endings and the effector cells, or at sensory nerve endings.

Acetylcholine↗
PubMed1971

Specificity of some ganglion stimulants.

1. The specificity of several ganglion stimulants has been tested on the isolated guinea-pig ileum by measuring the dose ratios produced by concentrations of hexamethonium.2. Most ganglion stimulants are also active at postganglionic receptors, some as blocking agents (for example, lobeline and dimethylphenylpiperazinium), others as agonists (for example, o-aminophenethyltrimethylammonium and, to a lesser extent, nicotine). The most specific ganglion stimulant, with the least activity at postganglionic receptors, was p-aminophenethyltrimethylammonium.3. The affinity constants of lobeline and dimethylphenylpiperazinium for the muscarine sensitive receptors in the guinea-pig ileum are 1.05 x 10(6) and 3.71 x 10(4), respectively.4. The antagonism of p-aminophenethyltrimethylammonium by hexamethonium gave results consistent with competition up to dose ratios of about 20. Such results could also be obtained if the antagonism were non-competitive, however, provided large responses could be obtained with less than about 5% of the receptors in the ganglia activated. The affinity constant of hexamethonium is about 2.6 x 10(5).5. It is suggested that the affinity of hexamethonium can largely be ascribed to hydrophobic bonding.

Animals↗
PubMed1974

Effects of lithium ions on electrical activity in sympathetic ganglia of the bullfrog.

1 The mode of action of lithium on electrical activity in the sympathetic ganglia of the bullfrog has been studied by recording extracellular and intracellular potential changes. Changes in nerve conduction and various types of synaptic transmission were studied when sodium ions in the external solution were totally replaced by equimolar concentrations of lithium ions and also when lithium ions were added to the external Ringer solution.2 Nerve conduction and nicotinic transmission in sympathetic ganglia were completely blocked in sodium-free sucrose solution, but were restored when the preparations were transferred to a sodium-free lithium solution.3 In the sodium-free lithium solution, the slow excitatory postsynaptic potential (e.p.s.p.) and muscarinic acetylcholine-depolarization were restored while the slow inhibitory postsynaptic potential (i.p.s.p.) and the muscarinic acetylcholine-hyperpolarization were not restored. Furthermore, the early after-discharges were accelerated and the inhibition of after-discharges was eliminated. These results support the hypothetical concept that the slow i.p.s.p. is generated by an activation of the electrogenic sodium pump.4 In the sodium-free lithium solution, restoration of nerve conduction and synaptic transmission were transient phenomena; both conduction and transmission were gradually blocked when preparations were soaked in the solution for long periods. The blockade appeared to be due to membrane depolarization.5 When lithium ions (20 mM) were added to the Ringer solution, nicotinic transmission was depressed. The slow e.p.s.p. was also depressed, but less so than the slow i.p.s.p. The early after-discharge was, however, accelerated; presumably due to the marked depression of the slow i.p.s.p. in this solution.6 Changes in synaptic transmission in Ringer solution containing lithium ions could be explained by membrane depolarization, a reduction of acetylcholine release and a depression of the electrogenic sodium pump.7 All results obtained in the present experiments could be explained by supposing that lithium ions are able to substitute for sodium ions in passive ionic membrane transport dependent on electrochemical energy but not in active ionic membrane transport dependent on metabolic energy.

Action Potentials↗