Functional and morphologic organization of stomach vegetative innervation

The functional and morphological organization of stomach vegetative innervation was studied. It is shown, that the sympathetic nerve strengthens vagal stimulation of motor activity of various departments of a stomach. In realization of the phenomenon participate preganglionic serotoninergic fibres transmitting excitation on ganglionic serotoninergic neurons. It is established, that stimulation of a wandering nerve results to degranulation of serotoninergic EC-cells carrying on the surface ganglionic 5-HT3,4-receptors. The irritation of a wandering nerve results in reduction of volume of EC-cells in older age.     

Neuropeptides as central integrators of autonomic nerve activity: effects of TRH, SRIF, VIP and bombesin on gastric and adrenal nerves

The nerve activity of the gastric ramus of the splanchnic (sympathetic) nerve, gastric ramus of the vagus, adrenal ramus of the splanchnic nerve and the superior laryngeal nerve (laryngeal ramus of vagus) were assessed before and after i.c.v. injection of neuropeptides in the rat. TRH stimulated the vagal branch but attenuated the sympathetic outflow to the stomach. In contrast, the sympathetic outflow to the adrenal was enhanced by TRH. SRIF suppressed the activity of all the nerves studied. VIP did not affect the sympathetic outflow to the stomach while suppressing the gastric branch of the vagus. The adrenal sympathetic branch as well as the superior laryngeal nerve was stimulated by VIP. Bombesin suppressed both vagal and sympathetic outflow to the stomach but markedly stimulated the laryngeal branch of the vagus. The adrenal sympathetic nerve was either stimulated or attenuated slightly by bombesin. These results indicate that centrally administered neuropeptides produce reactions specific for each nerve.     

Cardiac sympathetic nerve stimulation does not attenuate dynamic vagal control of heart rate via alpha-adrenergic mechanism

Complex sympathovagal interactions govern heart rate (HR). Activation of the postjunctional beta-adrenergic receptors on the sinus nodal cells augments the HR response to vagal stimulation, whereas exogenous activation of the presynaptic alpha-adrenergic receptors on the vagal nerve terminals attenuates vagal control of HR. Whether the alpha-adrenergic mechanism associated with cardiac postganglionic sympathetic nerve activation plays a significant role in modulation of the dynamic vagal control of HR remains unknown. The right vagal nerve was stimulated in seven anesthetized rabbits that had undergone sinoaortic denervation and vagotomy according to a binary white-noise signal (0-10 Hz) for 10 min; subsequently, the transfer function from vagal stimulation to HR was estimated. The effects of beta-adrenergic blockade with propranolol (1 mg/kg i.v.) and the combined effects of beta-adrenergic blockade and tonic cardiac sympathetic nerve stimulation at 5 Hz were examined. The transfer function from vagal stimulation to HR approximated a first-order, low-pass filter with pure delay. beta-Adrenergic blockade decreased the dynamic gain from 6.0 +/- 0.4 to 3.7 +/- 0.6 beats x min(-1) x Hz(-1) (P < 0.01) with no alteration of the corner frequency or pure delay. Under beta-adrenergic blockade conditions, tonic sympathetic stimulation did not further change the dynamic gain (3.8 +/- 0.5 beats x min(-1) x Hz(-1)). In conclusion, cardiac postganglionic sympathetic nerve stimulation did not affect the dynamic HR response to vagal stimulation via the alpha-adrenergic mechanism.     

Opposite effects of iv amiodarone on cardiovascular vagal and sympathetic efferent activities in rats

It is unknown whether amiodarone exerts a direct central action on the cardiovascular autonomic nervous system. This study was designed to evaluate the effects of acute amiodarone administration on vagal and sympathetic efferent nerve discharges. Experiments were carried out in 25 decerebrate unanesthetized rats. In one group, vagal activity was recorded from preganglionic fibers isolated from the cervical vagus nerve. In another group, sympathetic recordings were obtained from fibers isolated from the cervical sympathetic trunk in intact conditions or after barodenervation. Recordings were performed before and for 60 min after amiodarone (50 mg/kg iv) administration. In all groups, amiodarone induced bradycardia and hypotension. Vagal activity increased immediately, reaching a significant difference after 20 min (260 +/- 131% from 16.4 +/- 3.3 spikes/s) and was unmodified by the barodenervation. At difference, sympathetic activity after an initial and short-lasting increase (150 +/- 83% from 24.8 +/- 5.7 spikes/s) began to decrease significantly after 20 min (36 +/- 17%) throughout the experiment. The initial increase in sympathetic activity was not observed in barodenervated animals. These changes in vagal and sympathetic activity could play an important role in contributing to the antiarrhythmic action of amiodarone.     

Peptide YY reduces effects of sympathetic nerves and neuropeptide Y on cardiac vagal action.

In anesthetized dogs intravenous injection of neuropeptide Y (NPY) or stimulation of the cardiac sympathetic nerve is followed by a period of attenuation of vagal action at the heart lasting from many minutes to over an hour. Peptide YY (PYY), a related peptide (but one not reported to occur in the heart or its autonomic innervation), also inhibits cardiac vagal action but is more powerful and has a longer duration action. In 5 of 9 dogs, cardiac sympathetic nerve stimulation inhibited vagal action on the heart in control conditions, but relieved preexisting inhibition when repeated in the presence of PYY. In 3 dogs, exogenous NPY inhibited cardiac vagal action in control conditions, but failed to augment preexisting inhibition in the presence of PYY. An explanation offered for these results is that when PYY is occupying receptors on vagal nerve terminals, nerve-released NPY or exogenous NPY is either unable to produce an effect, because it cannot gain access to the receptors, or displaces PYY from at least some receptors and, being less powerful than PYY in its inhibitory action, lessens the preexisting vagal attenuation. The results reported are consistent with the proposal that the factor released from the sympathetic nerves following their stimulation and which is responsible for cardiac vagal inhibition is NPY.     

Neural control of jejunal and ileal motility and transmural potential difference in the ferret

The aim of the present study was to examine the vagal control of motor activity and transmural potential difference in the anaesthetized ferret jejunum and ileum in vivo. The data suggest that in the jejunum fluctuations in transmural potential difference occur secondary to spontaneous bursts of contractions and both are controlled by activity in the vagus nerve. However, in the ileum, spontaneous contractile activity and transmural potential difference are not under the tonic influence of the vagus nerve, although transmural potential difference may be under tonic sympathetic control. Furthermore, it appears that vagally induced motor activity and transmural potential difference responses are independent phenomena. Finally the changes in transmural potential difference and the long latency motor responses to vagal nerve stimulation in the small intestine of the ferret are mediated at least in part by noncholinergic transmitters.     

Neurochemical approaches to the prevention of ventricular fibrillation

Current evidence indicates that susceptibility to ventricular fibrillation (VF) can be reduced by decreasing cardiac sympathetic activity and by increasing vagal tone. Pharmacological agents that favor such a pattern of autonomic outflow protect the heart against fibrillation. These include morphine sulfate, clonidine, digitalis drugs, and bromocriptine. An intriguing new approach involves changing the serum concentration of amino acid precursors of the central neurotransmitters that modulate autonomic traffic. Considerable evidence indicates that accumulation of serotonin in the brain reduces sympathetic neural activity. When L-tryptophan or 5-hydroxytryptophan is administered with phenelzine (a monoamine oxidase inhibitor) and carbidopa (a selective peripheral L-amino acid decarboxylase inhibitor) to raise brain serotonin, a significant increase in myocardial electrical stability is observed. This effect results from a decrease in cardiac sympathetic tone as indicated by selective denervation and nerve recording studies. Enhancing serotoninergic neurotransmission can also significantly reduce vulnerability to VF during acute coronary artery occlusion. The effect of augmenting serotoninergic activity without the use of enzyme inhibitors has been investigated by administering agents such as melatonin, 5-methoxytryptophol, and 6-chloro-2-(1-piperazinyl) pyrazine (MK-212). Each of these substances increases cardiac electrical stability. The protective influence is unaffected by bilateral vagotomy but is blocked by the specific serotonin antagonist methergoline. Diminution of cardiac sympathetic drive appears to be the main mechanism of action. Thus, neurochemical interventions can exert a profound effect on cardiac electrical stability. Recent advances in neurochemistry and psychopharmacology promise new insights into the problem of sudden death and suggest a fresh approach for the management of life-threatening arrhythmias.     

Participation of alpha and beta adrenoreceptors in facilitating and inhibiting the action of the sympathetic nervous system in parasympathetic bradycardia

Electrical stimulation of the distal vagal cervical end in urethane chloralose anesthetized cats caused bradycardia that could be both enhanced and inhibited during sympathetic activation. Sympathetic activation was induced by electrical stimulation of the sympathetic outflow of the spinal cord at the level of Th 1-Th 3 in pitched cats or by an intravenous injection of tyramine. It has been proved pharmacologically that alpha-adrenoceptors are involved in potentiation. The inhibitory influences are realized via both alpha- and beta-adrenoceptors.     

Antiarrhythmic drugs and the modulation of autonomic control of heart rate in rabbits

A model of the components of autonomic control of heart rate was developed and used for the evaluation of quantitative contribution of sympathetic and vagal tone to cardiac function. In conscious rabbits, sequential inhibition of muscarinic and beta receptors was produced and the relative contributions of vagal and sympathetic tone were characterized. Based on the model, the magnitude of presynaptic interaction between the vagal and sympathetic nerve endings was evaluated. From data in the literature, similar analysis of the control of heart rate was performed for the rat, dog, and human subject and compared with that of the rabbit. The results show that the resting rabbit heart is under less vagal tone than sympathetic tone as compared with other species. The effects of acute administration of amiodarone on the sympathetic and parasympathetic control of heart rate as well as intrinsic heart rate were investigated. Amiodarone decreased the heart rate, which resulted from a direct effect on the sinoatrial (SA) node. In addition, it attenuated the vagal as well as the sympathetic effects on the SA node. The effect on vagal component was greater. Further, the effects of other antiarrhythmic drugs on the electrocardiographic PP and PR intervals were studied. The usefulness of this model for the analysis of the effects of antiarrhythmic drugs is presented.     

迷走神经和乙酰胆碱对缺血心肌保护作用的研究新进展

缺血性心脏病是危害人类健康的主要疾病之一。新近研究发现,心肌缺血与迷走神经活性降低及交感神经活性升高密切相关。本文从缺血性心脏病时心脏迷走神经调控的改变、迷走神经及其递质乙酰胆碱对缺血心肌的保护作用和其在缺血预适应、缺血后适应中可能的信号转导途径等方面,对迷走神经及其递质保护缺血心肌的作用机制研究的新进展予以综述,将有助于深入理解缺血性心脏病的发病机制及防治措施,为该疾病的防治开辟新思路。     

Contribution of cardiopulmonary baroreceptors to the control of the kidney.

The role of cardiopulmonary receptors in the control of renal sympathetic nerve activity and of renin release is reviewed. The evidence indicates that cardiopulmonary receptors with vagal afferents exert a tonic inhibition on both renal nerve activity and on renin release. The magnitude of this inhibition appears directly related to changes in blood volume. Atrial as well as ventricular receptors can influence the secretion of renin. Cardiopulmonary receptors with vagal afferents may also reflexly modulate renal prostaglandin secretion. There is preliminary evidence to suggest that cardiopulmonary receptors with sympathetic afferents can influence renal nerve activity. The limitations of previous studies are outlined and a direction for future studies is suggested. It is concluded that alterations in cardiopulmonary vagal afferent input and the resulting changes in renal nerve activity and in renin release are appropriate for the maintenance of blood volume homeostasis.     

Selective potentiating effect of RS14203 on a serotoninergic pathway in anesthetized rats

The usefulness of selective inhibitors of type 4 phosphodiesterase (PDE4) in the treatment of inflammation and pulmonary diseases is limited by their side effects: nausea and vomiting. We studied the effect of three structurally diverse PDE4 inhibitors on the vagal nerve afferent and efferent fibers in anesthetized rats. The effects of RS14203, (R)-rolipram, and CT-2450 were evaluated on the von Bezold-Jarisch reflex (vagal afferent fibers) and in a model of vagal electrical stimulation (vagal efferent fibers). All three PDE4 inhibitors were administered at 1, 10, or 100 microg/kg (iv) 15 min prior to the induction of bradycardia by an iv injection of 2-methyl-5-HT (von Bezold-Jarisch reflex) or by vagal electrical stimulation. At 100 microg/kg, RS14203 significantly potentiated the 2-methyl-5-HT response. No statistically significant effects were observed with (R)-rolipram or CT-2450 at the doses studied. RS14203, (R)-rolipram, or CT-2450 (1-100 microg/kg iv) did not affect the bradycardia induced by vagal electrical stimulation. Consequently, our results show that RS14203 selectively facilitates serotoninergic neurotransmission in vagal afferent fibers. The emetic action of RS14203 may be mediated by this mechanism.     

Electrical potentials of the vagal and sympathetic pathways of the stomach during elaboration of conditioned reflexes]

In chronic experiments on dogs discharges were recorded in efferent fibers of the vagal and splanchnic nerves and gastric branches of the solar plexus in the form of slow low-voltage and rapid high-voltage potentials. Alimentary conditioning to a previously indifferent stimulus produced a clear efferent reaction expressed in an increased number of oscillations. The magnitude of efferent electrical responses in all the examined structures is dissimilar and depends on the nerve nature (sympathetic or parasympathetic). The greatest electric reactions occur in the vagal gastric pathways.     

Isometric exercise modifies autonomic baroreflex responses in humans

The influence of brief, moderate isometric exercise on the earliest vagal and sympathetic responses to changes of afferent carotid baroreceptor activity was studied in 10 healthy young men and women. Vagal-cardiac nerve activity was estimated from changes of electrocardiographic R-R intervals, and postganglionic peroneal nerve muscle sympathetic activity was measured directly from microneurographic recordings. Carotid baroreceptor activity was altered with 5-s periods of 30 Torr pressure or suction applied to a neck chamber during held expiration. Brief handgrip (30% of maximum) significantly reduced base-line R-R intervals, did not modify reductions of R-R intervals during neck pressure, and significantly reduced increases of R-R intervals during neck suction. Handgrip did not significantly increase base-line sympathetic activity from resting levels, but it significantly diminished increases of sympathetic activity during neck pressure and augmented reductions of sympathetic activity during neck suction. Our results suggest that exercise modifies, in small but significant ways, early sympathetic and vagal responses to abrupt changes of arterial baroreceptor input in humans.     

Mechanism of the intracardiac interactions of the vagus and sympathetic nerves: is a serotoninergic mechanism possible?

A study was made of the conditions of the occurrence and mechanisms of the enhancement by the sympathetic nerve of the vagus-induced inhibition of rabbit heart work. It was discovered that to obtain such a phenomenon, it is necessary that stimulation of the stellate ganglion be made in the presence of perithreshold stimulation of the vagus after blockade of beta-adrenoreceptors. The inhibitory effect was not abolished by dihydroergotoxin but was blocked by promedol, aminazine and diprazine. It is suggested that the serotoninergic component is involved in the mechanism of the enhancement of the vagus-induced inhibition that occurs during stimulation of the sympathetic nerve.     

Changes in the electrical activity of the rabbit proximal colon in vivo by stimulation of the vagus and splanchnic nerves]

1. Using extracellular electrodes placed on the serosa, we recorded the modifications of the electrical activity of the colonic muslce fibers caused by the stimulation of vagal and splanchnic nerve fibers. 2. Vagal stimulation produces two types of junction potentials: excitatory junction potentials (EJPs) and inhibitory junction potentials (IJPs). The IJPs are elicited by stimulation of vagal fibers which innervate intramural non-adrenergic inhibitory neurons. 3. The conduction velocity of the nerve impulse along the vagal pre-ganglionic fibers is 1.01 m/sec for excitatory fibers and 0.5. m/sec for inhibitory fibers. 4. Splanchnic fiber stimulation causes EJP disappearance, blocking transmission between preganglionic fibers and intramural excitatory neurons, and a decrease in IJP amplitude that most likely indicates a previous hyperpolarization of the smooth muscle. 5. IJP persistence during splanchnic stimulation proves that sympathetic inhibition does not modify the transmission of the vagal influx onto the non-adrenergic inhibitory neurons of the intramural plexuses. 6. Through a comparative study of proximal and distal colonic innervation, we are able to show that there is a similar organization of both regions, that is a double inhibitory innervation: an adrenergic one of a sympathetic origin, and a non adrenergic one of a parasympathetic origin.     

电刺激迷走神经对蟾蜍心率和心率变异的影响

目的:观察不同频率迷走神经刺激对蟾蜍离体心脏的心率及心率变异的影响。方法:将蟾蜍心脏和右侧迷走交感干离体后,以不同频率电刺激神经,记录心电图曲线并作心率变异性(HRV)分析。结果:交感神经阻断后,电刺激迷走交感干,心率(HR)显著下降(P0.01),全部正常心动周期的标准差(SDNN)和相邻正常心动周期差值的均方根(RMSSD)显著升高(P0.01),不同频率刺激组之间没有明显差异;与对照组相比,各指标变化较大;给药组0.2Hz时高频(HF)显著升高(P0.01),低频/高频比值(LF/HF)明显降低(P0.05),0.8Hz时HF和LF/HF接近刺激前水平。结论:一定范围内增加刺激频率,迷走神经降低心率的作用增强;没有交感神经调节条件下的迷走神经对心率和心率变异的调节可能存在不同的机制。     

Oxidative stress impairs cardiac chemoreflexes in diabetic rats

We investigated the effects of diabetes mellitus and antioxidant treatment on the sensory and reflex function of cardiac chemosensory nerves in rats. Diabetes was induced by streptozotocin (STZ; 85 mg/kg ip). Subgroups of sham- and STZ-treated rats were chronically treated with an antioxidant, vitamin E (60 mg/kg per os daily, started 2 days before STZ). Animals were studied 6-8 wk after STZ injection. We measured renal sympathetic nerve activity (RSNA), mean arterial blood pressure (MABP), and cardiac vagal and sympathetic afferent activities in response to stimulation of chemosensitive sensory nerves in the heart by epicardial application of capsaicin (Caps) and bradykinin (BK). In cardiac sympathetic-denervated rats, Caps and BK (1-10.0 microg) evoked a vagal afferent mediated reflex depression of RSNA and MABP, which was significantly blunted in STZ-treated rats (P < 0.05). In vagal-denervated rats, Caps and BK (1-10.0 microg) evoked a sympathetic afferent-mediated reflex elevation of RSNA and MABP, which also was significantly blunted in STZ-treated rats (P < 0.05). Chronic vitamin E treatment effectively prevented these cardiac chemoreflex defects in STZ-treated rats without altering resting blood glucose or hemodynamics. STZ-treated rats with insulin replacement did not exhibit impaired cardiac chemoreflexes. In afferent studies, Caps and BK (0.1 g-10.0 microg) increased cardiac vagal and sympathetic afferent nerve activity in a dose-dependent manner in sham-treated rats. These responses were significantly blunted in STZ-treated rats. Vitamin E prevented the impairment of afferent discharge to chemical stimulation in STZ rats. The following were concluded: STZ-induced, insulin-dependent diabetes in rats extensively impairs the sensory and reflex properties of cardiac chemosensitive nerve endings, and these disturbances can be prevented by chronic treatment with vitamin E. These results suggest that oxidative stress plays an important role in the neuropathy of this autonomic reflex in diabetes.     

Vagal Nerve Stimulation Therapy: What Is Being Stimulated?

Vagal nerve stimulation in cardiac therapy involves delivering electrical current to the vagal sympathetic complex in patients experiencing heart failure. The therapy has shown promise but the mechanisms by which any benefit accrues is not understood. In this paper we model the response to increased levels of stimulation of individual components of the vagal sympathetic complex as a differential activation of each component in the control of heart rate. The model provides insight beyond what is available in the animal experiment in as much as allowing the simultaneous assessment of neuronal activity throughout the cardiac neural axis. The results indicate that there is sensitivity of the neural network to low level subthreshold stimulation. This leads us to propose that the chronic effects of vagal nerve stimulation therapy lie within the indirect pathways that target intrinsic cardiac local circuit neurons because they have the capacity for plasticity.     

尾核P物质对胃运动的抑制效应系通过黑质,迷走背核经迷走神经所介导

本工作观察损毁下丘脑外侧区,黑质,迷走背核及其传出神经对尾核微量注射Ｐ物质引起的胃肌电快波和胃运动抑制效应的影响。实验结果：该抑制效应不依赖于下丘脑外侧区的完整但可被损毁黑质,迷走背核或迷走上所消除。用利血平耗竭交感神经递质则不影响该效应。这些结果表明：尾核ＳＰ的抑胃效应系通过黑质、迷走背核经迷走神经所传出。