Role of the autonomic nervous system in the development of cardiovascular changes during nasal apnoea and lung inflation.

The role of the sympathetic system in the development of bradycardia during nasal apnoea and the role of the sympathetic and parasympathetic system in the development of cardiovascular changes during and immediately after lung inflation were determined in anaesthetized rabbits. Transection of the cervical cord (C5-7) completely blocked the hypertensive response to chemical stimulation of the nasal mucosa. The degree of nasal bradycardia was 72% lower than in stimulation of the controls. Propranolol had no effect on the hypertensive reaction, but inhibited nasal bradycardia, which was 68% lower than in the controls. Lung inflation induced tachycardia, which was only non-significantly reduced by bilateral vagotomy. Vagotomy inhibited the bradycardiac response to removal of occlusion of the trachea and the subsequent rise in blood pressure, however. Cervical cord transection likewise did not reduce inflation-induced tachycardia, but it significantly influenced the heart rate during the second phase of prolonged inflation, when the heart is affected by hypoxia. Inflation-induced tachycardia was likewise not influenced by bilateral vagotomy associated with cervical cord transection. Similar cardiac responses also occur in the presence of the simple increase in pericardial pressure produced by left pneumothorax without lung inflation.     

Central and peripheral mechanisms underlying gastric distention inhibitory reflex responses in hypercapnic-acidotic rats

We have observed that in chloralose-anesthetized animals, gastric distension (GD) typically increases blood pressure (BP) under normoxic normocapnic conditions. However, we recently noted repeatable decreases in BP and heart rate (HR) in hypercapnic-acidotic rats in response to GD. The neural pathways, central processing, and autonomic effector mechanisms involved in this cardiovascular reflex response are unknown. We hypothesized that GD-induced decrease in BP and HR reflex responses are mediated during both withdrawal of sympathetic tone and increased parasympathetic activity, involving the rostral (rVLM) and caudal ventrolateral medulla (cVLM) and the nucleus ambiguus (NA). Rats anesthetized with ketamine and xylazine or α-chloralose were ventilated and monitored for HR and BP changes. The extent of cardiovascular inhibition was related to the extent of hypercapnia and acidosis. Repeated GD with both anesthetics induced consistent falls in BP and HR. The hemodynamic inhibitory response was reduced after blockade of the celiac ganglia or the intraabdominal vagal nerves with lidocaine, suggesting that the decreased BP and HR responses were mediated by both sympathetic and parasympathetic afferents. Blockade of the NA decreased the bradycardia response. Microinjection of kainic acid into the cVLM reduced the inhibitory BP response, whereas depolarization blockade of the rVLM decreased both BP and HR inhibitory responses. Blockade of GABA(A) receptors in the rVLM also reduced the BP and HR reflex responses. Atropine methyl bromide completely blocked the reflex bradycardia, and atenolol blocked the negative chronotropic response. Finally, α(1)-adrenergic blockade with prazosin reversed the depressor. Thus, in the setting of hypercapnic-acidosis, a sympathoinhibitory cardiovascular response is mediated, in part, by splanchnic nerves and is processed through the rVLM and cVLM. Additionally, a vagal excitatory reflex, which involves the NA, facilitates the GD-induced decreases in BP and HR responses. Efferent chronotropic responses involve both increased parasympathetic and reduced sympathetic activity, whereas the decrease in BP is mediated by reduced α-adrenergic tone.     

Nonuniformity in the von Bezold-Jarisch reflex

The von Bezold-Jarisch reflex (BJR) is a vagally mediated chemoreflex from the heart and lungs, causing hypopnea, bradycardia, and inhibition of sympathetic vasomotor tone. However, cardiac sympathetic nerve activity (CSNA) has not been systematically compared with vasomotor activity during the BJR. In 11 urethane-anesthetized (1-1.5 g/kg iv), artificially ventilated rats, we measured CSNA simultaneously with lumbar sympathetic activity (LSNA) while the BJR was evoked by right atrial bolus injections of phenylbiguanide (0.5, 1.0, 1.5, and 2 microg). Nerve and heartbeat responses were analyzed by calculating normalized cumulative sums. LSNA and heartbeats were always reduced by the BJR. An excitatory "rebound" component often followed the inhibition of LSNA but never outweighed it. For CSNA, however, excitation usually (in 7 of 11 rats) outweighed any initial inhibition, such that the net response to phenylbiguanide was excitatory. The differences in net response between LSNA, CSNA, and heartbeats were all significant (P < 0.01). A second experimental series on seven rats showed that methyl atropine (1 mg/kg iv) abolished the bradycardia of the BJR, whereas subsequent bilateral vagotomy substantially reduced LSNA and CSNA responses, both excitatory and inhibitory. These findings show that, during the BJR, 1) CSNA is often excited, 2) there may be coactivation of sympathetic and parasympathetic drives to the heart, 3) divergent responses may be evoked simultaneously in cardiac vagal, cardiac sympathetic, and vasomotor nervous pathways, and 4) those divergent responses are mediated primarily by the vagi.     

Leucine-enkephalin interrupts sympathetically mediated tachycardia prejunctionally in the canine sinoatrial node

This study examined the role of leucine-enkephalin (LE) in the sympathetic regulation of the cardiac pacemaker. LE was administered by microdialysis into the interstitium of the canine sinoatrial node during either sympathetic nerve stimulation or norepinephrine infusion. In study one, the right cardiac sympathetic nerves were isolated as they exit the stellate ganglion and were stimulated to produce graded (low, 20-30 bpm; high 40-50 bpm) increases in heart rate (HR). LE (1.5 nmoles/min) was added to the dialysis inflow and the sympathetic stimulations were repeated after 5 and 20 min of LE infusion. After 5 min, LE reduced the tachycardia during sympathetic stimulation at both low (18.2 +/- 1.3 bpm to 11.4 +/- 1.4 bpm) and high (45 +/- 1.5 bpm to 22.8 +/- 1.5 bpm) frequency stimulations. The inhibition was maintained during 20 min of continuous LE exposure with no evidence of opioid desensitization. The delta-opioid antagonist, naltrindole (1.1 nmoles/min), restored only 30% of the sympathetic tachycardia. Nodal delta-receptors are vagolytic and vagal stimulations were included in the protocol as positive controls. LE reduced vagal bradycardia by 50% and naltrindole completely restored the vagal bradycardia. In Study 2, additional opioid antagonists were used to determine if alternative opioid receptors might be implicated in the sympatholytic response. Increasing doses of the kappa-antagonist, norbinaltorphimine (norBNI), were combined with LE during sympathetic stimulation. NorBNI completely restored the sympathetic tachycardia with an ED50 of 0.01 nmoles/min. A single dose of the micro -antagonist, CTAP (1.0 nmoles/min), failed to alter the sympatholytic effect of LE. Study 3 was conducted to determine if the sympatholytic effect was prejunctional or postjunctional in character. Norepinephrine was added to the dialysis inflow at a rate (30-45 pmoles/min) sufficient to produce intermediate increases (35.2 +/- 1.8 bpm) in HR. LE was then combined with norepinephrine and responses were recorded at 5-min intervals for 20 min. The tachycardia mediated by added norepinephrine was unaltered by LE or LE plus naltrindole. At the same 5-min intervals, LE reduced vagal bradycardia by more than 50%. This vagolytic effect was again completely reversed by naltrindole. Collectively, these observations support the hypothesis that the local nodal sympatholytic effect of LE was mediated by kappa-opioid receptors that reduced the effective interstitial concentration of norepinephrine and not the result of a postjunctional interaction between LE and norepinephrine.     

Regulation of cardiac rhythm in hibernating mammals

The dramatic fall in heart rate exhibited by mammals entering hibernation begins before there is any noticeable fall in body temperature. The initial, progressive decrease in heart rate is the result of a cyclic parasympathetic activation that induces skipped beats and regular asystoles as well as slows the even heart beat. As body temperature subsequently falls, the parasympathetic influence is progressively withdrawn and periods of parasympathetic and sympathetic dominance alternate and give rise to regular periods of arrhythmia (tachycardia followed by bradycardia), and occasional long asystoles or periods of highly irregular cardiac activity. Superimposed on this is a vagally-mediated, respiratory sinus arrhythmia that is accentuated in species that breathe episodically. These events give way to a uniform heart rate in deep hibernation at low temperatures where both parasympathetic and sympathetic tone appear absent. The complete absence of tone is not a function of reduced temperature but is reflective of the state of deep, steady state hibernation. The elevation in heart rate that accompanies the onset of arousal is the result of dramatic increases in sympathetic activation that precede any increases in body temperature. As body temperature then rises, sympathetic influence is slowly withdrawn. Arrhythmias are also common during natural arousals or shifts from lower to warmer hibernation temperatures as periods of parasympathetic and sympathetic dominance again alternate en route to re-establishing a steady state in euthermia. The mechanism behind, and the biological significance of, cardiac changes mediated through orchestrated arrhythmias remain unknown.     

Atrial natriuretic factor alters autonomic interactions in the control of heart rate in conscious rats

Regulation of heart rate was studied in rats receiving either i.v. saline at 64 microL/min or synthetic 28-residue rat atrial natriuretic peptide (ANF) at a dose sufficient to decrease mean arterial blood pressure by 10%. Autonomic influences were deduced from steady-state heart rate responses of each group to propranolol, atropine, or propranolol and atropine combined. A multiplicative model of heart rate control was used to derive quantitatively from the data the modulation of intrinsic heart rate by sympathetic and parasympathetic mechanisms. Animals receiving ANF showed a lower heart rate than control animals. This relative bradycardia was abolished by atropine. Blocking of sympathetic effects with propranolol had no effect on basal heart rate in either group, and atropinization led to significant increases in heart rate in both groups of rats. Mathematical analysis of the results showed that the bradycardia produced by ANF was due predominantly to a reduced intrinsic heart rate and to enhanced vagal inhibition of postganglionic sympathetic activity. Parasympathetic contribution to heart rate in the absence of sympathetic activity was negligible in control rats and small during ANF. We conclude that the major influences of ANF on heart rate control are a decrease of intrinsic heart rate and enhanced parasympathetic inhibition of postganglionic presynaptic sympathetic activity.     

Baroreceptor mechanisms in rat

Baroreflex control of cardiovascular parameters was studied in control, atropine- and guanethidine-treated rats. Baroreceptor activity was tested by the relationship between the increase in blood pressure produced by a phenylephrine administration (bolus ov infusion) and the induced bradycardia. No differences were observed in basal arterial blood pressure and heart rate between treated- and control rats. Baroreceptor sensitivity was lower in atropine- or guanethidine-treated rats than in control animals. Baroreceptor activity has two components: a first, rapid, predominantly parasympathetic and a second, slower, that is mediated by both parasympathetic and sympathetic efferent pathways.     

Cardiovascular reflex-reactions on the blood volume changes before and after pharmacological elimination of the efferent heart innervation]

Reflex changes in the heart frequency, blood pressure and respiratory frequency induced by slow changes of the blood volume are observed in the aesthetized European hamster (Cricetus cricetus L.). Tachycardia, hypertension and hyperpnoe occured during intravenous infusion and bradycardia, hypotension and respiratory inhibition during hemorrhages or local distensions of the junction between the superior vena cava and the right atrium. Various receptor organs of the heart and the great vessels and sympathetic as well as parasympathetic effector mechanisms were involved in the reflex effects. An activation of efferent vagal fibers decreased blood pressure and heart frequency; an excitation of efferent sympathetic fibers increased blood pressure and heart frequency.     

Diet-induced obesity severely impairs myelinated aortic baroreceptor reflex responses

Diet-induced obesity (DIO) attenuates the arterial cardiac baroreceptor reflex, but the mechanisms and sites of action are unknown. This study tested the hypothesis that DIO impairs central aortic baroreceptor pathways. Normal chow control (CON) and high-fat-chow obesity-resistant (OR) and obesity-prone (OP) rats were anesthetized (inactin, 120 mg/kg) and underwent sinoaortic denervation. The central end of the aortic depressor nerve (ADN) was electrically stimulated to generate frequency-dependent baroreflex curves (5-100 Hz) during selective activation of myelinated (A-fiber) or combined (A- and C-fiber) ADN baroreceptors. A mild stimulus (1 V) that activates only A-fiber ADN baroreceptors induced robust, frequency-dependent depressor and bradycardic responses in CON and OR rats, but these responses were completely abolished in OP rats. Maximal activation of A fibers (3 V) elicited frequency-dependent reflexes in all groups, but a dramatic deficit was still present in OP rats. Activation of all ADN baroreceptors (20 V) evoked even larger reflex responses. Depressor responses were nearly identical among groups, but OP rats still exhibited attenuated bradycardia. In separate groups of rats, the reduced heart rate (HR) response to maximal activation of ADN A fibers (3 V) persisted in OP rats following pharmacological blockade of β(1)-adrenergic or muscarinic receptors, suggesting deficits in both parasympathetic nervous system (PNS) and sympathetic nervous system (SNS) reflex pathways. However, the bradycardic responses to direct efferent vagal stimulation were similar among groups. Taken together, our data suggest that DIO severely impairs the central processing of myelinated aortic baroreceptor control of HR, including both PNS and SNS components.     

Interactions within the intrinsic cardiac nervous system contribute to chronotropic regulation

The objective of this study was to determine how neurons within the right atrial ganglionated plexus (RAGP) and posterior atrial ganglionated plexus (PAGP) interact to modulate right atrial chronotropic, dromotropic, and inotropic function, particularly with respect to their extracardiac vagal and sympathetic efferent neuronal inputs. Surgical ablation of the PAGP (PAGPx) attenuated vagally mediated bradycardia by 26%; it reduced heart rate slowing evoked by vagal stimulation superimposed on sympathetically mediated tachycardia by 36%. RAGP ablation (RAGPx) eliminated vagally mediated bradycardia, while retaining the vagally induced suppression of sympathetic-mediated tachycardia (-83%). After combined RAGPx and PAGPx, vagal stimulation still reduced sympathetic-mediated tachycardia (-47%). After RAGPx alone and after PAGPx alone, stimulation of the vagi still produced negative dromotropic effects, although these changes were attenuated compared with the intact state. Negative dromotropic responses to vagal stimulation were further attenuated after combined ablation, but parasympathetic inhibition of atrioventricular nodal conduction was still demonstrable in most animals. Finally, neither RAGPx nor PAGPx altered autonomic regulation of right atrial inotropic function. These data indicate that multiple aggregates of neurons within the intrinsic cardiac nervous system are involved in sinoatrial nodal regulation. Whereas parasympathetic efferent neurons regulating the right atrium, including the sinoatrial node, are primarily located within the RAGP, prejunctional parasympathetic-sympathetic interactions regulating right atrial function also involve neurons within the PAGP.     

Cardiogenic reflexes after immune injury of the heart

Afferent and efferent spike activity from the parasympathetic (vagus) and sympathetic cardiac nerves were recorded simultaneously with ECG, and indices of heart function were measured in acute experiments on anesthetized dogs, which allowed us to study the modifications of cardio-cardiac reflex influences after a local immune heart injury. After an injury nidus has been formed in the heart, cardiogenic depressor reflexes evoked by an intracoronary application of veratrine or bradykinin were considerably suppressed or even abolished, and afferent spike activity in the vagus cardiac nerves noticeably decreased. At the same time, both the facilitation of activity in sympathetic afferent fibers and pressor reflex effects were preserved after the heart injury. Different localization of vagus and sympathetic afferent structures in the heart and their specialized sensitivity to the biologically active substances are suggested as the factors determining the pattern of cardiogenic reflex influences after a heart injury.Neirofiziologiya/Neurophysiology, Vol. 27, No. 1, pp. 18–25, January–February, 1995.     

Mechanical action of the atria during stimulation on the work of the sinus node

The cardiac pacemaker and atria were removed from the frog heart and placed into a chamber with Ringer solution. Atrial pacing was performed at a suprathreshold milliamperage. The mechanism of changes in the cardiac pacemaker during atrial pacing was studied both under the conditions of the blockade of the intracardiac nervous system and elimination of the bioelectrical and mechanical effects of the atria on the cardiac pacemaker. It is inferred that the change in the rate of pacemaker stimulation during atrial pacing is largely determined by the mechanical activity of the atria.     

Baroreflex responses to electrical stimulation of aortic depressor nerve in conscious SHR

Baroreflex responses to changes in arterial pressure are impaired in spontaneously hypertensive rats (SHR). Mean arterial pressure (MAP), heart rate (HR), and regional vascular resistances were measured before and during electrical stimulation (5-90 Hz) of the left aortic depressor nerve (ADN) in conscious SHR and normotensive control rats (NCR). The protocol was repeated after beta-adrenergic-receptor blockade with atenolol. SHR exhibited higher basal MAP (150 +/- 5 vs. 103 +/- 2 mmHg) and HR (393 +/- 9 vs. 360 +/- 5 beats/min). The frequency-dependent hypotensive response to ADN stimulation was preserved or enhanced in SHR. The greater absolute fall in MAP at higher frequencies (-68 +/- 5 vs. -38 +/- 3 mmHg at 90-Hz stimulation) in SHR was associated with a preferential decrease in hindquarter (-43 +/- 5%) vs. mesenteric (-27 +/- 3%) resistance. In contrast, ADN stimulation decreased hindquarter and mesenteric resistances equivalently in NCR (-33 +/- 7% and -30 +/- 7%). Reflex bradycardia was also preserved in SHR, although its mechanism differed. Atenolol attenuated the bradycardia in SHR (-88 +/- 14 vs. -129 +/- 18 beats/min at 90-Hz stimulation) but did not alter the bradycardia in NCR (-116 +/- 16 vs. -133 +/- 13 beats/min). The residual bradycardia under atenolol (parasympathetic component) was reduced in SHR. MAP and HR responses to ADN stimulation were also preserved or enhanced in SHR vs. NCR after deafferentation of carotid sinuses and contralateral right ADN. The results demonstrate distinct differences in central baroreflex control in conscious SHR vs. NCR. Inhibition of cardiac sympathetic tone maintains reflex bradycardia during ADN stimulation in SHR despite impaired parasympathetic activation, and depressor responses to ADN stimulation are equivalent or even greater in SHR due to augmented hindquarter vasodilation.     

Reflex changes in heart rate during chemoreceptor stimulation in monkeys

The changes in heart rate induced by the stimulation of arterial chemoreceptors by apneic asphyxia and left atrial - intracarotid injections of sodium cyanide were investigated in anesthetized artificially ventilated and paralysed monkeys. Apneic asphyxia and sodium cyanide injection caused tachycardia, bradycardia, or both in monkeys paralysed with decamethonium bromide and tachycardia only, in monkeys paralysed with gallamine. In both groups, the tachycardia was abolished by prior administration of propranolol and the bradycardia, by atropine. Prior ventilation with 100% O2 abolished the heart rate responses produced by apnea. Recording of phrenic efferent activity showed that the neural discharge increased in response to apneic asphyxia and sodium cyanide injections. It remained so during the manifestation of tachycardia, bradycardia, or no change in heart rate, suggesting that even though "higher centres" may have an important influence in the heart rate responses elicited, central respiratory drive may not be the only mechanism. The present results show that in the nonhuman primate, arterial chemoreceptor stimulation elicits both cardioacceleratory and cardioinhibitory reflexes, and the net effect of their stimulation on heart rate depends upon the balance between these opposing mechanisms.     

Reflex regulation of the circulation after stimulation of cardiac receptors by prostaglandins

Prostaglandins (PGs) are potent vasoactive substances that may participate in the control of coronary blood flow, platelet aggregation, and inflammation. An important action of PGs may be the stimulation of c fibers in general and vagal cardiac c fibers in particular. The Bezold-Jarisch reflex after intracoronary injection of Veratrum alkaloids is very similar to the vagal bradycardia elicited by stimulation of cardiac PG synthesis or injection of prostacyclin (PGI2). The characteristic features of this reflex are 1) stimulation of c fibers, 2) inferoposterior wall location of receptors, 3) vagal afferents, 4) vagal efferents to the heart, 5) sympathetic efferents to peripheral blood vessels, and 6) interaction with other reflexes. Vagal cardiac c fibers are activated by intracoronary injections of PGI2 or arachidonic acid, resulting in a vagal reflex bradycardia and hypotension due to withdrawal of peripheral alpha-adrenergic tone to resistance vessels. The cardiac receptors are located predominantly in the inferoposterior wall of the left ventricle. When stimulated by PGs, cardiac receptors may also modify the regulation of arterial pressure by the baroreflexes, altering the inverse relationship between systemic arterial pressure and heart rate. Thus, there is a striking parallelism between the veratridine-induced Bezold-Jarisch reflex and PG-induced cardiac reflexes, although the physiological and clinical significance of these reflexes remains to be determined.     

Pituitary adenylate cyclase-activating polypeptide: localization and differential influence on isolated hearts from rats and guinea pigs

This study was done to determine if pituitary adenylate cyclase-activating peptide (PACAP)-immunoreactive nerve fibers occur in cardiac muscle as well as intracardiac ganglia of rats and guinea pigs and to clarify the chronotropic actions of PACAP27 in the same species using isolated heart preparations. PACAP nerve fibers were not detected in atrial or ventricular muscle of rat or guinea pig but a few stained nerve fibers occurred in the atrioventricular bundle of the guinea pig. Stained nerve fibers were prominent in intracardiac ganglia of both species. PACAP27 caused a dose-dependent tachycardia in isolated rat hearts (+39 +/- 3 beats/min with 1 nmol, n = 6). Positive and/or negative chronotropic responses were evoked by PACAP27 in guinea pig heart, depending on dose and prior exposure to the peptide. PACAP27 also caused arrhythmias in several guinea pig hearts. Treatment with atropine eliminated or prevented PACAP-evoked bradycardia and arrhythmias, implicating cholinergic neurons in these responses. Positive chronotropic responses to PACAP were unaffected by beta-adrenergic receptor blockade in either species, suggesting that tachycardia resulted from a direct action on the heart. These observations support the conclusion that endogenous PACAP could have a role in regulating parasympathetic input to the heart but through different mechanisms in rats versus guinea pigs. A direct positive chronotropic influence of endogenous PACAP is unlikely since atrial muscle lacks PACAP-immunoreactive nerve fibers.     

Inhibitory effects of excess sympathetic activity on parasympathetic vasodilation in the rat masseter muscle

The present study was designed to examine the effect of sympathetic tonic activity on parasympathetic vasodilation evoked by the trigeminal-mediated reflex in the masseter muscle in urethane-anesthetized rats. Sectioning of the superior cervical sympathetic trunk (CST) ipsilaterally increased the basal level of blood flow in the masseter muscle (MBF). Electrical stimulation of the peripheral cut end of the CST for 2 min using 2-ms pulses ipsilaterally decreased in a dependent manner the intensity (0.5-10 V) and frequency (0.1-5 Hz) of the MBF. The CST stimulation for 2 min at <0.5 Hz with 5 V using 2-ms pulses seems to be comparable with the spontaneous activity in the CST fibers innervating the masseter vasculature, because this stimulation restored the basal level of the MBF to the presectioned values. Parasympathetic vasodilation evoked by electrical stimulation of the central cut end of the lingual nerve in the masseter muscle was markedly reduced by CST stimulation for 2 min with 5 V using 2-ms pulses in a frequency-dependent manner (0.5-5 Hz). Intravenous administration of phentolamine significantly reduced the vasoconstriction induced by CST stimulation in a dose-dependent manner (0.1-1 mg/kg), but pretreatment with either phentolamine or propranolol failed to affect the sympathetic inhibition of the parasympathetic vasodilation. Our results suggest that 1) excess sympathetic activity inhibits parasympathetic vasodilation in the masseter muscle, and 2) alpha- and beta-adrenoceptors do not contribute to sympathetic inhibition of parasympathetic vasodilation, and thus some other types of receptors must be involved in this response.     

Modulation of cardiopulmonary depressor reflex in nucleus ambiguus by electroacupuncture: roles of opioids and γ-aminobutyric acid

Stimulation of cardiopulmonary receptors with phenylbiguanide (PBG) elicits depressor cardiovascular reflex responses, including decreases in blood pressure and heart rate mediated in part by the brain stem parasympathetic cardiac neurons in the nucleus ambiguus (NAmb). The present study examined NAmb neurotransmitter mechanisms underlying the influence of electroacupuncture (EA) on the PBG-induced hypotension and bradycardia. We hypothesized that somatic stimulation during EA modulates PBG responses through opioid and γ-aminobutyric acid (GABA) modulation in the NAmb. Anesthetized and ventilated cats were studied during repeated stimulation with PBG or cardiac vagal afferents while low-frequency EA (2 Hz) was applied at P5-6 acupoints overlying the median nerve for 30 min and NAmb neuronal activity, heart rate, and blood pressure were recorded. Microinjection of kainic acid into the NAmb attenuated the PBG-induced bradycardia from -60 ± 11 to -36 ± 11 beats/min. Likewise, EA reduced the PBG-induced depressor and bradycardia reflex by 52 and 61%, respectively. Cardiac vagal afferent evoked preganglionic cellular activity in the NAmb was reduced by EA for about 60 min. Blockade of opioid or GABA(A) receptors using naloxone and gabazine reversed the EA-related modulation of the evoked cardiac vagal activity by 73 and 53%, respectively. Similarly, naloxone and gabazine reversed EA modulation of the negative chronotropic responses from -11 ± 5 to -23 ± 6 and -13 ± 4 to -24 ± 3 beats/min, respectively. Thus EA at P5-6 decreases PBG evoked hypotension and bradycardia as well as the NAmb PBG-sensitive preganglionic cardiac vagal outflow through opioid and GABA neurotransmitter systems.     

Does heart rate differentiate neurotic from normal people in a conditional reflex test?

This study is to compare heart reactivity between normals and anxiety neurotic patients. Five male and five female patients with anxiety neurosis and four male and five female normal persons were submitted to classic delayed conditional reflexes with different probabilities of reinforcement (shock), to a defensive instrumental conditional reflex, and to a neutral nonreinforced stimulus. The basal heart frequency was higher in neurotics and in women than in normals and men. The conditional stimulus (CS) associated with a shock generally produced a bradycardia in normal individuals and in neurotic men, but a tachycardia in neurotic women (effects most pronounced in cases with 100% shock probability). The instrumental CS caused a tachycardia in all of the groups, with highest values in neurotic women. The neutral stimulus produced bradycardia in all persons. The aftereffect of the light stimulus depended on whether a shock was administered and on the CS. The differences between neurotics and normals are explained as caused by the heightened excitatory level of the CNS of the neurotic group, produced by the unspecific activating effect of chronic anxiety, and differences of plastic processes in both groups, resulting in different effects of phasic anxiety on the heart. Complex inhibitory-excitatory interactions of the sympathetic and the vagal system underlying the heart rate changes may be assumed. Possible mechanisms leading to sex differences are discussed.     

Effects of glucagon-like peptide-1, yohimbine, and nitrergic modulation on sympathetic and parasympathetic activity in humans

Glucagon-like peptide-1 (GLP-1), an incretin, which is used to treat diabetes mellitus in humans, inhibited vagal activity and activated nitrergic pathways. In rats, GLP-1 also increased sympathetic activity, heart rate, and blood pressure (BP). However, the effects of GLP-1 on sympathetic activity in humans are unknown. Our aims were to assess the effects of a GLP-1 agonist with or without alpha(2)-adrenergic or -nitrergic blockade on autonomic nervous functions in humans. In this double-blind study, 48 healthy volunteers were randomized to GLP-1-(7-36) amide, the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-l-arginine acetate (l-NMMA), the alpha(2)-adrenergic antagonist yohimbine, or placebo (i.e., saline), alone or in combination. Hemodynamic parameters, plasma catecholamines, and cardiac sympathetic and parasympathetic modulation were measured by spectral analysis of heart rate. Thereafter, the effects of GLP-1-(7-36) amide on muscle sympathetic nerve activity (MSNA) were assessed by microneurography in seven subjects. GLP-1 increased (P = 0.02) MSNA but did not affect cardiac sympathetic or parasympathetic indices, as assessed by spectral analysis. Yohimbine increased plasma catecholamines and the low-frequency (LF) component of heart rate power spectrum, suggesting increased cardiac sympathetic activity. l-NMMA increased the BP and reduced the heart rate but did not affect the balance between sympathetic and parasympathetic activity. GLP-1 increases skeletal muscle sympathetic nerve activity but does not appear to affect cardiac sympathetic or parasympathetic activity in humans.