Behavioural changes induced in conscious mice by intracerebroventricular injection of catecholamines, acetylcholine and 5-hydroxytryptamine.

1 In anaesthetized rats electrical stimulation of the intact cervical sympathetic nerve produced frequency-dependent lower eyelid contractions and tachycardia. 2 The tachycardia was caused by excitation of efferent fibres since it was equally evident in the pithed rat preparation, and the right nerve was more effective than the left. By contrast, no differences were seen between the responses to right and left vagal stimulation in either rats or rabbits. 3 Guanethidine inhibited both cardiac and eyelid responses, propranolol only the former and phentolamine only the latter, therby revealing the adrenergic nature of the nerves. Hexamethonium caused partial inhibition and the block was intensified by atropine. 4 The inferior eyelid of mice, guinea-pigs and rabbits as well as the nictitating membrane of rabbits and cats were contracted by cervical sympathetic nerve stimulation. In these species too, tachycardia occurred; this was more pronounced with the right than the left sympathetic nerve. The order of cardiac responsiveness was mouse greater than rat greater than guinea-pig greater than rabbit greater than cat. 5 In guinea-pigs histamine-induced bronchoconstriction was reduced by cervical sympathetic nerve stimulation. 6 That discrete cardiac pathways exist in the cervical sympathetic nerves is suggested by the reproducibility of the effects within any one species. The accessibility of the nerves greatly simplifies the examination of drugs in vivo on two different structures innervated by the sympathetic nervous system.     

CENTRAL REGULATION OF AUTONOMIC FUNCTION: NO BRAKES?

1. Nitric oxide (NO) is formed by neuronal NO synthase (nNOS) and acts as a non-conventional neurotransmitter in the brain. A growing body of evidence supports the hypothesis that NO acts to decrease sympathetic output to the periphery; these effects may occur at several autonomic sites. The present review describes studies from our laboratory that address this hypothesis. 2. Restraint stress activates putative NO-producing neurons in many autonomic centres: preoptic area, medial septum, amygdala, hypothalamus, including the paraventricular nucleus (PVN), raphe nuclei, nucleus tractus solitarius (NTS) and ventrolateral medulla (VLM). These results suggest that NO is directly or indirectly involved in regulating sympathetic output to the periphery. 3. Systemic angiotensin II (Angll) activates putative NO-producing neurons in the PVN. These neurons may be activated either by the increases in arterial pressure that accompany Angll injections or due to activation of AngII-containing neural pathways. 4. Hypotension is associated with the activation of putative NO-producing PVN neurons, small numbers of which also project to the NTS or VLM. As the majority of activated neurons is in the magnocellular division, NO production may be related to the production of vasopressin. 5. Adult spontaneously hypertensive rats (SHR) show increased gene expression of nNOS in the hypothalamus, dorsal medulla and caudal VLM. These differences are not present in young prehypertensive SHR, suggesting that the changes in gene expression in adult rats are associated with the increased sympathetic nerve activity found in these rats. 6. Gene expression of nNOS is altered in the hypothalamus and caudal VLM of renal hypertensive rats at 3 and 6 weeks after surgical induction of hypertension. Contrasting results at the two time points may be due to differing underlying physiological processes that characterize the two stages of renal hypertension. 7. Nitric oxide may affect sympathetic output through several possible mechanisms. These include affecting production of the second messenger cGMP and interactions with more classical neurotransmitters or with neurohormonal systems in the brain.     

心肌缺血与交感神经传入的研究进展

心脏的自主神经包括交感神经与副交感神经。支配心脏的交感神经不仅有传出轴突,也有传递心脏感受的传入神经。心肌缺血可激活心交感传入神经并将信息传递到大脑心血管中枢,通过兴奋交感传出神经引起交感兴奋性反射,出现心率加快和血压升高等现象使心肌缺血、缺氧和心绞痛加重。因此,交感神经功能变化可加重心肌缺血损伤。     

Inhibition of cardiac sympathetic neurotransmission by adenosine

Experiments were performed to study the effect of adenosine on sympathetic neurotransmission to the myocardium. Adenosine administration to pentobartial-anesthetized dogs resulted in decrerease in blood pressure and significant impairment of cardioacceleration produced of stimulation of cardiac sympathetic nerves. The positive chronotropic effect of intravenous norepinephrine was not affected by adenosine. The blood pressure lowering as well as the inhibitory effect of adenosine on cardiac sympathetic nerve function could be significantly antagonized by theophylline. These results provide in vivo evidence in support of the hypothesis that adenosine caused inhibition of sympathetic neurotransmission via an action on purinergic receptors located on sympathetic nerve terminals.     

Mechanisms of sympathetic activation in heart failure

1. Heart Failure (HF) is a serious, debilitating condition with poor survival rates and an increasing level of prevalence. A characteristic of HF is a compensatory neurohumoral activation that increases with the severity of the condition. 2. The increase in sympathetic activity may be beneficial initially, providing inotropic support to the heart and peripheral vasoconstriction, but in the longer term it promotes disease progression and worsens prognosis. This is particularly true for the increase in cardiac sympathetic nerve activity, as shown by the strong inverse correlation between cardiac noradrenaline spillover and prognosis and by the beneficial effect of beta-adrenoceptor antagonists. 3. Possible causes for the raised level of sympathetic activity in HF include altered neural reflexes, such as those from baroreceptors and chemoreceptors, raised levels of hormones, such as angiotensin II, acting on circumventricular organs, and changes in central mechanisms that may amplify the responses to these inputs. 4. The control of sympathetic activity to different organs is regionally heterogeneous, as demonstrated by a lack of concordance in burst patterns, different responses to reflexes, opposite responses of cardiac and renal sympathetic nerves to central angiotensin and organ-specific increases in sympathetic activity in HF. These observations indicate that, in HF, it is essential to study the factors causing sympathetic activation in individual outflows, in particular those that powerfully, and perhaps preferentially, increase cardiac sympathetic nerve activity.     

LEFT ATRIAL RECEPTOR INHIBITION OF CARDIAC EFFERENT VAGAL ACTIVITY IN THE DOG

1. The tachycardia produced by atrial receptor stimulation has been reported to be ‘solely’ due to an increased sympathetic activity, but not inhibitable by propranolol. We examined the effect of left atrial balloon inflation in chloralose-anaesthetized dogs on heart rate with and without propranolol (l. Omg/kg) and on the activity in single cardiac efferent fibres of the vagus nerve. 2. Propranolol reduced the cardiac response to balloon inflation by one-third, but did not abolish the tachycardia. Efferent cardiac vagal activity was 3.8 ± 0.4 spikes/s and 2.3 ± 0.7 spikes/s prior to and during balloon inflation respectively. 3. It was concluded that the left atrial receptors produce a tachycardia by decreasing cardiac parasympathetic and increasing sympathetic efferent activities.     

PRESYNAPTIC INHIBITION BY SEROTONIN OF CARDIAC SYMPATHETIC TRANSMISSION IN DOGS

1. The effect of serotonin on cardiac sympathetic transmission was investigated in vagotomized and cardiac decentralized dogs. 2. Administration of serotonin in doses of 10-100 μg/kg i.v., during the resting unstimulated state caused tachycardia and pressor responses which were inhibited by cyproheptadine but not by guanethidine. The tachycardia was reduced by a β-adrenoceptor antagonist, bufetolol. 3. Serotonin in doses of 3-100 μg/kg depressed the elevated heart rate during maintained electrical stimulation of the cardiac sympathetic nerves. 4. Cyproheptadine did not antagonize the serotonin-induced depression of the stimulation-elevated heart rate, while desipramine attenuated but did not abolish it. 5. Serotonin did not have a significant effect on the heart rate elevated by maintained infusion of noradrenaline. 6. The present results suggest that serotonin-induced depression of heart rate during sympathetic nerve stimulation is due to presynaptic inhibition by serotonin of cardiac sympathetic transmission which is not mediated via‘classic’ tryptaminergic receptors.     

Cardiovascular actions of an experimental antitumor agent,homoharringtonine, in anesthetized dogs

Cardiovascular actions of homoharringtonine, a plant extract currently being tested for clinical efficacy as an antitumor agent, were investigated in anesthetized mongrel dogs. Intravenous administration of homoharringtonine (4 mg/M²) produced significant reductions in heart rate, cardiac output, and arterial blood pressure, while myocardial contractility or total peripheral resistance were not altered. These results suggest that the bradycardia could account for decreases in both cardiac output and blood pressure. In additional experiments performed to evaluate the actions of homoharringtonine on cardiac sympathetic neurotransmission it was discovered that this compound caused significant impairment of the tachycardia elicited during stimulation of cardiac sympathetic nerves. The positive chronotropic effects of either norepinephrine or isoproterenol were not altered by homoharringtonine. In these animals in which both vagi and the right cardioaccelerator nerve were sectioned, the hypotensive and bradycardiac effects were of lesser magnitude than that seen in neurally intact animals. These results show that a dose of homoharringtonine comparable to that used in clinical trials produces hypotension and bradycardia which may result from inhibition of sympathetic nerve function caused by the compound.     

Impulse interval-dependent effect of sympathetic nerve stimulation on evoked acetylcholine release from the rabbit perfused atria preparation

The aim of the present study was to explore possible prejunctional effects mediated by impulse activity of sympathetic terminals on evoked acetylcholine release in an organ innervated by the autonomic ground plexus. Rabbit atria were isolated with the extrinsic right vagus and sympathetic nerves intact and perfused with Tyrode solution. Acetylcholine overflow was determined after labelling of the transmitter stores with [¹⁴C]choline and fractionation of the radioactivity on cation exchange columns. The overflow of endogenous noradrenaline was measured by HPLC and electrochemical detection.The vagus nerve was stimulated at 2 Hz for 3 min four times at intervals of 10 min. During the second stimulation the postganglionic sympathetic nerves were stimulated (2 Hz, 3 min) in such a way that the impulses preceded the vagus stimuli by a fixed time interval which was varied in different experiments (0, 7, 19, 50, 132, and 350 ms). Evoked acetylcholine release was significantly enhanced when the vagus was excited 7, 19 and 50 ms after the sympathetic nerves but it was unaltered at the 132 or 350 ms intervals, and when both nerves were stimulated simultaneously. Noradrenaline release was similar (about 6 ng per stimulation period) in all experimental groups. When sympathetic nerve stimulation had little effect in releasing noradrenaline (<2.0 ng per stimulation period), facilitation of acetylcholine release at the 19 ms pulse interval was absent. The resting outflow of acetylcholine was unaffected by sympathetic nerve stimulation.The experiments show a facilitation of evoked acetylcholine release by sympathetic activity. As revealed by the pulse-to-pulse method this effect is confined to a relatively brief interval immediately following the excitation of the noradrenergic terminal, and is unlikely to be mimicked by exogenous drug application.     

Inhibitory effects of clonidine on responses to sympathetic nerve stimulation in the pithed rat.

1. The spinal sympathetic outflow to the eyelid, heart, splanchnic blood vessels, vas deferens and anococcygeus muscle was stimulated in pithed rats. 2. Clonidine inhibited sympathetic outflow to all of the tissues studied. The inhibitory effects of clonidine on cardiac nerves and hypogastric nerves were antagonized by phentolamine. 3. Clonidine produced a postsynaptic alpha-adrenoceptor agonist action on the eyelid, splanchnic blood vessels and the anococcygeus muscle. These effects were also antagonized by phentolamine. 4. The effects of clonidine, naphazoline and oxymetazoline on pre- and postsynaptic alpha-adrenoceptors were determined. 5. The presynaptic alpha-adrenoceptors employed were situated in either the sympathetic cardiac or hypogastric nerve terminals. Increases in diastolic blood pressure were used to assess concurrent postsynaptic alpha-adrenoceptor agonist activity. 6. The presynaptic alpha-adrenoceptor agonist potencies of clonidine, naphazoline and oxymetazoline were very similar on cardiac nerve terminals whereas on the hypogastric nerve terminals oxymetazoline was about 6 times more potent than either naphazoline or clonidine. 7. The results support the view that presynaptic alpha-adrenoceptors regulate transmitter release in sympathetic nerves. There appear to be subtle differences between the presynaptic alpha-adrenoceptors of different sympathetic nerve endings.     

Reflexly evoked coactivation of cardiac vagal and sympathetic motor outflows: observations and functional implications

1. The purpose of the present review is to highlight the pattern of activity in the parasympathetic and sympathetic nerves innervating the heart during their reflex activation. 2. We describe the well-known reciprocal control of cardiac vagal and sympathetic activity during the baroreceptor reflex, but point out that this appears to be the exception rather than the rule and that many other reflexes reviewed herein (e.g. peripheral chemoreceptor, nociceptor, diving response and oculocardiac) involve simultaneous coactivation of both autonomic limbs. 3. The heart rate response during simultaneous activation of cardiac autonomic outflows is unpredictable because it does not simply reflect the summation of opposing influences. Indeed, it can result in bradycardia (peripheral chemoreceptor, diving and corneal), tachycardia (nociceptor) and, in some circumstances, can predispose to malignant arrhythmias. 4. We propose that this cardiac autonomic coactivation may allow greater cardiac output during bradycardia (increased ventricular filling time and stronger contraction) than activation of the sympathetic limb alone. This may be important when pumping blood into a constricted vascular tree, such as is the case during the peripheral chemoreceptor reflex and the diving response.     

Anti-nicotinic and anti-muscarinic actions of eperisone in the isolated canine atrium

The effects of eperisone, an antispastic agent, on the chronotropic and inotropic responses to acetylcholine, nicotine or stimulation of intracardiac autonomic nerves were evaluated in isolated, blood-perfused canine atrium. Eperisone (10-300 micrograms) injected into the sinus node artery of the isolated atrium produced dose-related negative chronotropic and inotropic effects, which were not affected by atropine. In the same doses, eperisone inhibited the negative chronotropic and inotropic responses to an injection of acetylcholine and intracardiac parasympathetic stimulation. Eperisone also suppressed the negative followed by positive cardiac responses to nicotine, but did not modify the positive responses to intracardiac sympathetic stimulation or norepinephrine. The inhibitory effect persisted much longer for the responses to nicotine or parasympathetic stimulation than for those to acetylcholine. These results suggest that eperisone at doses that induce direct cardiac depressant effects exerts its blocking action on nicotinic receptors at parasympathetic ganglia and sympathetic nerve terminals and on muscarinic receptors at the effector cells in the dog heart.     

Differential control of cardiac and sympathetic vasomotor activity from the dorsomedial hypothalamus

1. The dorsomedial hypothalamus (DMH) plays a crucial role in mediating the cardiovascular responses to different stressors, including acute psychological stress and cold stress. Activation of neurons in the DMH evokes increases in arterial pressure and in the activity of sympathetic nerves innervating the heart, blood vessels and brown adipose tissue. The descending pathways from the DMH to the spinal sympathetic outflow include synapses with neurons in medullary nuclei and possibly other brain stem regions. 2. Recent studies from our and other laboratories have indicated that neurons in the rostral ventrolateral medulla (RVLM) and in the region of the raphe pallidus (RP) in the medulla are important components of the descending pathways that mediate the cardiovascular response to activation of the DMH. Neurons in the RP primarily mediate the sympathetic cardiac components of the DMH-evoked response, whereas the RVLM neurons primarily mediate the sympathetic vasomotor component. 3. Activation of DMH neurons not only increases heart rate and sympathetic vasomotor activity, but also resets the baroreceptor reflex such that it remains effective, without any decrease in sensitivity, over a higher operating range of arterial pressure. 4. Activation of 5-hydroxytryptamine 5-HT(1A) receptors in the medulla oblongata leads to a selective suppression of cardiac and sympathetic vasomotor components of the DMH-evoked response, but does not affect sympathetic reflex responses evoked from baroreceptors or chemoreceptors. Thus, central 5-HT(1A) receptors modulate cardiovascular responses evoked from the DMH in a highly potent but selective fashion.     

Effects of clonidine on canine cardiac neuroeffector structures controlling heart rate

1 In intact dogs anaesthetized with pentobarbitone, clonidine (10 μg/kg, i.v.) produced a sustained decrease in heart rate. This effect was significantly smaller in vagotomized dogs in which the sympathetic drive to the heart was either left intact or experimentally created by continuous electrical stimulation of the decentralized cardioaccelerator nerve. In the latter preparation, the negative chronotropic action of clonidine was reversed by an intravenous injection of phentolamine, whereas in the former experimental situation it was antagonized only by an intravenous plus an intravertebral artery injection of phentolamine.

2 In dogs with denervated hearts the tachycardia produced by electrical stimulation of the cardioaccelerator nerve was accompanied by a rise in noradrenaline overflowing into the coronary sinus plasma. Clonidine inhibited both these effects and phentolamine restored them to pre-clonidine levels.

3 Clonidine decreased heart rate in dogs with an intact parasympathetically innervated heart and decentralized stellate ganglia. When the low basal heart rate of this preparation was elevated by electrical stimulation of the cardioaccelerator nerve, clonidine had a negative chronotropic effect, the degree of which was similar to that observed in intact dogs.

4 Clonidine neither modified baseline heart rates of dogs with denervated hearts nor the levels of heart rate which in this preparation were reduced by a sustained electrical stimulation of the right vagus or increased by intravenous infusions of either isoprenaline or noradrenaline.

5 These findings indicate that in the intact dog, bradycardia induced by clonidine resulted both from a reduction of sympathetic drive and from a concomitant increase in parasympathetic tone. The latter action did not occur at the level of cardiac neuroeffector structures since it was observed only in the presence of centrally connected vagal pathways. The inhibition of cardiac sympathetic tone was of both peripheral and central origin. Clonidine, in fact, diminished the quantity of noradrenaline overflowing into the coronary sinus plasma in cardiac denervated dogs with a tachycardia elicited by electrical stimulation of the decentralized cardioaccelerator nerve. This peripheral effect was probably due to an activation of α-adrenoceptors located on sympathetic nerve terminals since it was antagonized by phentolamine. However, in vagotomized dogs (intact sympathetic pathways) intravenous phentolamine failed to antagonize the heart rate effects of clonidine which were abolished by a subsequent injection of phentolamine into the vertebral artery. Thus, the clonidine-induced inhibition of both the peripheral and central sympathetic drive to the heart would appear to be mediated via α-adrenoceptors.

     

Inhibition by prostaglandins of adrenergic transmission in the left ventricular myocardium of anesthetized dogs

In the intact left ventricle of pentobarbital-anesthetized dogs, we have investigated the influence of prostaglandins on cardiac adrenergic neuroeffector events. The positive inotropic response (dP/dtmax) and the coronary sinus output of norepinephrine (NE) elicited by left cardiac sympathetic nerve stimulation as well as the contractile response produced by intracoronary injections of NE were studied before and after prostaglandin synthesis inhibition, and also before and during intracoronary infusion of PGE2 and PGI2. Cardiac sympathetic nerve stimulation (1-4 Hz) and intracoronary injections of NE (30-120 ng/kg) produced frequency- and dose-related positive inotropic effects, respectively. Administration of indomethacin (10 mg/kg i.v.) augmented the increase in left ventricular dP/dtmax elicited by left cardiac sympathetic nerve stimulation or intracoronary NE injection. In indomethacin pretreated dogs, intracoronary PGE2 (30 ng kg-1 min-1) or PGI2 (60 ng kg-1 min-1) attenuated the positive inotropic effect produced by left cardiac sympathetic nerve stimulation or intracoronary injections of NE. The increase in coronary sinus output of NE elicited by cardiac sympathetic nerve stimulation was enhanced by indomethacin and attenuated during intracoronary infusion of PGE2 and PGI2. These data suggest that prostaglandins synthesized in the heart inhibit cardiac adrenergic transmission in the left ventricle in vivo by reducing release of NE elicited by left cardiac sympathetic nerve stimulation and also by attenuating the action of the neurotransmitter at effector cells.     

Differential regulation of brown adipose and splanchnic sympathetic outflows in rat: roles of raphe and rostral ventrolateral medulla neurons

1. The medullary premotor neurons determining the sympathetic outflow regulating cardiac function and vasoconstriction are located in the rostral ventrolateral medulla (RVLM). The present study sought evidence for an alternative location for the sympathetic premotor neurons determining the sympathetic nerve activity (SNA) controlling brown adipose tissue (BAT) metabolism and thermogenesis. 2. The tonic discharge on sympathetic nerves is determined by the inputs to functionally specific sympathetic preganglionic neurons from supraspinal populations of premotor neurons. Under normothermic conditions, BAT SNA was nearly silent, while splanchnic (SPL) SNA, controlling mesenteric vasoconstriction, exhibited sustained large-amplitude bursts. 3. The rostral raphe pallidus (RPa) contains potential sympathetic premotor neurons that project to the region of sympathetic preganglionic neurons in the thoracic spinal cord. Disinhibition of neurons in RPa elicited a dramatic increase in BAT SNA, with only a small rise in SPL SNA. 4. Splanchnic SNA was strongly influenced by the baroreceptor reflex, as indicated by a high coherence with the arterial pressure wave, a significant amplitude modulation over the time-course of the cardiac cycle and a marked inhibition of SPL SNA during a sustained increase in arterial pressure. When activated, the bursts in BAT SNA exhibited no correlation with arterial pressure and were not affected by increases in arterial pressure. 5. Because these characteristics and reflex responses in sympathetic outflow have been shown to arise from the on-going or altered discharge of sympathetic premotor neurons, the marked differences between SPL and BAT SNA provide strong evidence supporting the hypothesis that vasoconstriction and thermogenesis (metabolism) are controlled by distinct populations of sympathetic premotor neurons, the former in the RVLM and the latter, potentially, in the RPa.     

Block by capsaicin of voltage-gated K+ currents in melanotrophs of the rat pituitary.

1 The present study compares the effects on representative autonomic outflows of IVth ventricular application of tryptamine analogues which act at 5-HT1 receptors with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). 2 Cumulative doses of 8-OH-DPAT, N,N-di-n-propyl-5-carboxamidotryptamine (DP-5-CT) and 5-carboxamidotryptamine (5-CT, 2.5-40 nmol kg-1), sumatriptan (10-160 nmol kg-1), indorenate (100-800 nmol kg-1), 5-hydroxytryptamine (5-HT, 20-640 nmol kg-1) both alone and in the presence of cinanserin (0.1 mg kg-1) were given into the IVth ventricle of cats which were anaesthetized with a mixture of alpha-chloralose and pentobarbitone sodium, neuromuscularly blocked and artificially ventilated. Recordings were made of arterial blood pressure, heart rate, renal, cardiac, splanchnic and phrenic nerve activities, femoral arterial flow, tracheal and intragastric pressures. 3 Central application of each of the agonists evoked significant falls in arterial blood pressure. In addition 8-OH-DPAT, DP-5-CT, 5-CT and 5-HT all evoked a differential inhibition of sympathetic nerve activities, with renal nerve activity being the most sensitive and cardiac nerve activity the least sensitive. In the dose-ranges used, administration of sumatriptan evoked reductions only in renal and splanchnic nerve activities whilst indorenate reduced activity in all three sympathetic nerves to a similar extent. 4 The effect of the agonists on heart rate was more inconsistent than the effects on sympathetic outflow.(ABSTRACT TRUNCATED AT 250 WORDS)     

Innervation of the large intestine of the toad (bufo marinus)

The morphology, physiology and pharmacology of the innervation of the toad (Bufo marinus) large intestine have been studied. The large intestine can be divided into the regions colon, rectum and cloaca, on morphological grounds, but acts as a unit in response to nerve stimulation. Of the right and left nerves, each appears to supply the entire large intestine. Autonomic innervation of the large intestine of Bufo marinus is as follows: (1) The 9th and 10th spinal nerves (pelvic) contain predominantly excitatory preganglionic cholinergic fibres, but some inhibitory adrenergic fibres are also present in most preparations. (2) The splanchnic nerves contain inhibitory postganglionic adrenergic fibres from the 3rd to 5th sympathetic ganglia, and a small number of excitatory cholinergic fibres. The pathway of adrenergic inhibitory fibres to the large intestine alongside the posterior mesenteric artery as seen in mammals is rarely present in the toad. Several nonspecific actions of autonomic drugs on the large intestine are discussed. The functional organization of the autonomic innervation of the toad large intestine is similar to that in mammals, that is the large intestine is controlled by antagonistic cholinergic and adrenergic nerves. However, the separation of these two types of nerve fibres into anatomically distinct nerves does not appear to be as complete as in mammals. It is suggested that inhibitory autonomic control of the alimentary canal in vertebrates first appears in the hind-gut region.     

ROLE OF THE HYPOTHALAMIC PARAVENTRICULAR NUCLEUS IN CARDIOVASCULAR REGULATION

1. The paraventricular hypothalamic nucleus (PVH) is a complex structure with both neuroendocrine and autonomic functions. It is a major source of vasopressin and the primary source of corticotropin-releasing factor. In addition, parvicellular PVH neurons have reciprocal connections with brain-stem autonomic centres and directly innervate sympathetic preganglionic neurons. Evidence is reviewed which indicates that in conscious rats PVH activation increases blood pressure, heart rate, renal nerve activity and plasma renin activity. 2. In conscious rats, a non-hypotensive haemorrhage (13 mL/kg blood loss over 24 min) results in increased numbers of Fos-immunoreactive cell nuclei within both magnocellular and parvicellular PVH neurons, including the ventral medial parvicellular regions known to contain neuronal projections to brainstem autonomic centres and spinal cord sympathetic preganglionic neurons. 3. Cell-selective ibotenate lesions of the parvicellular PVH significantly blunt the corticosterone response but do not alter blood pressure, heart rate or plasma renin concentration response to non-hypotensive or hypotensive haemorrhage. This and earlier studies indicate that, while the PVH is necessary for the corticosterone response and contributes to increased vasopressin release during blood loss, it does not play an important role in the sympathetic nervous system and renin-angiotensin responses to hypovolaemia and hypotension. 4. There is evidence to indicate that the parvicellular PVH serves as a necessary relay for cardiovascular and renin responses to certain behavioural stressors. We propose that cardiovascular information relayed to parvicellular PVH autonomic regions may be used to modulate behavioural, rather than homeostatic, effects on haemodynamics and renin release.     

Vagal nerve modulation: a promising new therapeutic approach for cardiovascular diseases

The physiological activities of the mammalian heart are regulated by the autonomic nervous system. An imbalanced autonomic nervous system with increased sympathetic tone and reduced vagal tone has been implicated in cardiovascular diseases. Experimental and clinical reports have demonstrated that vagal nerve activation is able to improve outcomes for multiple cardiovascular diseases, such as ischaemic heart disease, heart failure, arrhythmia and hypertension. In this paper, we mainly focus on the potential cardioprotective mechanisms of vagal nerve activation. Based on the knowledge gained from our experiments and other published reports, vagal activation results in cardioprotection is not only associated with heart rate, anti-adrenergic effect but also related to anti-inflammatory activity, regulation of cellular redox states and regulation of mitochondrial targets. In conclusion, vagal nerve activation may be a promising new therapeutic approach for the treatment of cardiovascular diseases.