Brainstem activation of the adrenal medulla in the cat

Stimulation of the locus coeruleus in 40 cats leads to generalized activation of the sympathetic nervous system characterized by an immediate pressor response which was followed in the post-stimulus period by an increase of 49 ± 10and44 ± 6% in common carotid arterial resistance ipsilateral and contralateral to stimulation, respectively. This later response was not affected by vagotomy or bilateral cervical sympathectomy but was blocked by high spinal cord section. The post-stimulus carotid vasoconstriction response could be entirely eliminated by acute bilateral physiological adrenalectomy in the form of adrenal hilar clamping, an effect which was reversible if the clamps were removed. The carotid vasoconstrictor response was associated with a rise in the circulating level of noradrenaline (260%) and adrenaline (196%), which was prevented by clamping the adrenal hilum. This response was not mediated via the hypothalamus because it persisted in the decerebrate animal, nor was it merely excitation of fibers of passage since it was reproduced by microinjection of glutamate into the locus coeruleus. The response was blocked by phentolamine suggesting it is mediated by α-adrenoceptors. These data represent the first conclusive demonstration that cell bodies in the brainstem are capable of activating the adrenal medulla. This fact is central to our present concept of the organization of the sympatho-adrenal axis.     

Effects of 6-hydroxydopamine and the PNMT inhibitor LY134046 on pressor responses to stimulation of the subretrofacial nucleus in anaesthetized stroke-prone spontaneously hypertensive rats

The subretrofacial nucleus of the rostral ventrolateral medulla is an important site for the control of sympathetic vasomotor tone and is the location of the C1 PNMT-containing cell bodies. In the present study the involvement of central monoaminergic neurons in the pressor responses evoked by chemical or electrical stimulation of this nucleus was examined in urethane-anaesthetized stroke-prone spontaneously hypertensive rats (SHRSP). Vehicle-treated rats were compared to animals treated with the PNMT inhibitor LY134046, the catecholamine neurotoxin 6-hydroxydopamine (6-OHDA) or a combination of 6-OHDA and the serotonin neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). LY134046 caused a 43% depletion of adrenaline content in the hypothalamus and medulla but not in the spinal cord but had no effect on the pressor responses to stimulation of the subretrofacial nucleus. However, intraventricular administration of 6-OHDA reduced the pressor responses to subretrofacial nucleus stimulation by 50%. 6-OHDA caused profound depletion of noradrenaline in the brain and spinal cord, and adrenaline in the hypothalamus. Combined treatment with 6-OHDA and 5,7-DHT caused the additional depletion of serotonin to 34% and 13% in the hypothalamus and spinal cord, respectively, but caused no further reduction of pressor responses than with 6-OHDA alone. These results suggest that the pressor responses elicited by subretrofacial nucleus stimulation involve a 6-OHDA-sensitive pathway (presumably catecholaminergic) other than the bulbospinal adrenaline pathway but that serotonergic mechanisms do not contribute.     

Importance of spinal noradrenergic pathways in cardiovascular reflexes and central actions of clonidine and alpha-methyldopa in the rabbit

We have examined in conscious rabbits the chronic effects of 6-hydroxydopamine (6-OHDA)-induced local lesions of the spinal noradrenaline (NA) pathways on (i) resting mean arterial pressure (MAP) and heart rate (HR), (ii) the nasopharyngeal pressor response, (iii) the sympathetic component of the baroreceptor-heart rate reflex (iv) the acute responses to intracisternal (i.c.) clonidine and alpha-methyldopa (alpha-MD), and (v) the acute NA release response produced by i.e. 6-OHDA. One month after injection of 6-OHDA (40 nmol in 4 microliters) into the first cervical spinal cord segment (C1), the NA content was reduced to 29% in C2, 45% in T4 and 61% in L3 with little non-specific damage. Basal MAP was 14% higher (P less than 0.05) than in sham-operated rabbits suggesting increased vasoconstrictor tone. Basal cardiac sympathetic tone was enhanced, but a corresponding increase in cardiac vagal tone resulted in little net effect on resting HR in the spinal NA-depleted group. Spinal NA lesions attenuated the nasopharyngeal pressor reflex by 27% in baroreceptor-intact rabbits and by 38% in sino-aortically denervated (SAD) animals. The lesion did not affect HR range, gain and BP50 of the sympathetic baroreflex. In SAD rabbits, the acute MAP responses to i.c. 6-OHDA (early hypotension, late hypertension) were not affected by spinal NA depletion, but the early fall in HR (cardiac sympathetic inhibition) was abolished. The hypotension produced by i.c. clonidine or alpha-MD was not affected by the lesion, probably because many of the NA terminals in the lower thoracic and upper lumbar cord were still intact. Our results suggest that intraspinal NA fibers have a tonic inhibitory action on spinal preganglionic vasoconstrictor and cardiac motoneurons. The spinal NA neurons affecting vasomotor tone (but not cardiac sympathetic tone) are in turn inhibited by higher vasomotor centers receiving projections from the arterial and trigeminal afferents and thereby participate in vasoconstrictor reflexes.     

An investigation into the mechanism of cardiovascular responses elicited by electrical stimulation of locus coeruleus and subcoeruleus in the cat

Electrical stimulation of locus coeruleus (LC) and subcoeruleus (SC) elicited an increase in heart rate (HR) and blood pressure (BP). Adrenergic neurone blockade in the posterior hypothalamus with guanethidine and also bilateral adrenalectomy completely blocked the LC stimulation induced cardiovascular responses. The cardiovascular responses elicited by electrical stimulation of SC were, however, unaffected by the former and only partially inhibited by the latter. It is suggested that the LC stimulation-evoked rise in HR and BP is mediated by catecholamine release from the adrenal medulla due to an activation of the hypothalamic-adrenal axis. The cardiovascular responses elicited by stimulation of SC are mainly due to activation of the sympathetic preganglionic neurones and are further augmented by the adrenal catecholamine release.     

Cardiovascular responses elicited by fastigial and hypothalamic stimulation in conscious cats

The cardiovascular responses to stimulation within a fastigial nucleus of the cerebellum and the defence reaction area of the hypothalamus were tested in 3 conscious cats in whom chronic indwelling electrodes had been inserted stereotaxically into the brain at previous aseptic operation. At the same time, indwelling catheters had been inserted into the aorta for recording arterial pressure, and into the superior vena cava for intravenous injections of phenyl diguanide and other drugs. Rise of aortic pressure and tachycardia occurred when stimulating either site at strengths of stimulation below the threshold of somatic movements. Bradycardia of reflex origin (phenyl diguanide, noradrenaline) was inhibited during the stimulations and this was not due to the onset of an equal and opposite tachycardia of sympathetic origin. These results of stimulation are the same in the anaesthetized animal, but were obtained at lower stimulus threshold. They are not an artefact of anaesthesia.     

Contribution of forebrain noradrenaline innervation to the central circulatory effects of alpha-methyldopa and 6-hydroxydopamine

We studied the circulatory effects of chronic lesions of the ascending noradrenergic (NA) projections to the forebrain on the acute effects of intracisternal (i.c.) alpha-methyldopa (alpha-MD) and 6-hydroxydopamine (6-OHDA) on mean arterial pressure (MAP) and heart rate (HR) in conscious rabbits with arterial baroreceptors either intact or denervated (sinoaortic denervation, SAD). Both drugs acutely release neurotransmitter from central NA neurons. I.c. 6-OHDA produced acute hypertension and bradycardia while i.c. alpha-MD produced acute hypotension and bradycardia. The responses are qualitatively similar in SAD rabbits except that after 6-OHDA, HR increased. In another group we studied the effects of the drugs 3-4 weeks after localised injections of 6-OHDA in the midbrain dorsal and ventral NA bundles. Local 6-OHDA depleted forebrain regions of NA by 44-76%, and had no effects on basal values of MAP or HR. The pressor and depressor effects, of 6-OHDA and alpha-MD respectively, were little affected by the lesions in either intact or SAD rabbits. By contrast, in rabbits with intact baroreceptors, the lesion abolished the bradycardia produced by i.c. alpha-MD and 6-OHDA. The latter drug now produced a late tachycardia. In SAD rabbits, however, there was no effect on the alpha-MD-induced bradycardia, but the 6-OHDA tachycardia was enhanced. Since the major effects of the lesions were confined to the rabbits with intact baroreceptor afferents, it suggests that the ascending NA pathways are important for the cardiac responses dependent on baroreceptor input. In intact animals, both drugs produce bradycardia through facilitation of the vagal component of the baroreceptor-heart rate reflex. In SAD rabbits, almost all the changes to HR are mediated through the cardiac sympathetic and the lesions have little effect on HR.     

Lesions of the ventromedial hypothalamic nucleus enhance sympatho-adrenal function

The effects of lesions of the ventromedial hypothalamic nucleus (VMH) on the sympatho-adrenal function were investigated in anesthetized rats using electrophysiological and biochemical techniques. Lesions of this nucleus produced a gradual but strong increase in the efferent activity of the adrenal sympathetic nerves. Catecholamine secretion from the adrenal medulla was also facilitated by VMH lesions. The results indicate that the catecholamines from the adrenal medulla might be involved in the development of metabolic disorders seen during VMH syndrome.     

Spinal sympathoexcitatory pathways activated by stimulating fastigial nuclei,hypothalamus, and lower brain stem in cats

In anesthetized cats electrical stimulation of a fastigial (medial cerebellar) nucleus caused discharges in sympathetic nerves which were accompanied by cardiovascular system responses, including rise in arterial blood pressure, increased pulse pressure, and tachycardia. The pathways mediating the excitatory autonomic effects of fastigial origin descend bilaterally in the dorsolateral column of the spinal cord in the region between the lateral corticospinal tract and the central grey substance. Similar influences from the hypothalamus and medullary reticular substance are also mediated through fibers descending in the same region of spinal dorsolateral white matter. Local lesions in the spinal cord abolish the discharges in inferior cardiac, splanchnic, and renal nerves which could be evoked from all three sources, and the spontaneous activity of these sympathetic nerves was also reduced. The lesions did not alter intercostal nerve-evoked activity nor prevented its spreading to segments above or below the lesions.     

Complex negative emotions induced by electrical stimulation of the human hypothalamus

BackgroundStimulation of the ventromedial hypothalamic region in animals has been reported to cause attack behavior labeled as sham-rage without offering information about the internal affective state of the animal being stimulated.ObjectiveTo examine the causal effect of electrical stimulation near the ventromedial region of the human hypothalamus on the human subjective experience and map the electrophysiological connectivity of the hypothalamus with other brain regions.MethodsWe examined a patient (Subject S20_150) with intracranial electrodes implanted across 170 brain regions, including the hypothalamus. We combined direct electrical stimulation with tractography, cortico-cortical evoked potentials (CCEP), and functional connectivity using resting state intracranial electroencephalography (EEG).ResultsRecordings in the hypothalamus did not reveal any epileptic abnormalities. Electrical stimulations near the ventromedial hypothalamus induced profound shame, sadness, and fear but not rage or anger. When repeated single-pulse stimulations were delivered to the hypothalamus, significant responses were evoked in the amygdala, hippocampus, ventromedial-prefrontal and orbitofrontal cortices, anterior cingulate, as well as ventral-anterior and dorsal-posterior insula. The time to first peak of these evoked responses varied and earliest propagations correlated best with the measures of resting-state EEG connectivity and structural connectivity.ConclusionThis patient's case offers details about the affective state induced by the stimulation of the human hypothalamus and provides causal evidence relevant to current theories of emotion. The complexity of affective state induced by the stimulation of the hypothalamus and the profile of hypothalamic electrophysiological connectivity suggest that the hypothalamus and its connected structures ought to be seen as causally important for human affective experience.     

Vasodilatation in hind-limb skeletal muscle evoked as part of the defence reaction in the rat

Electrical stimulation of the hypothalamic and mid-brain defence area of the rat's brain elicits a consistent cardiovascular pattern of response of which vasodilatation in the skeletal muscle is an integral component: the mechanisms mediating this vasodilatation were investigated. It is not sensitive to atropine in this species, but it was substantially affected, particularly its later stage (the prolonged tail-end of the response), by either beta-adrenoreceptor antagonists (propranolol, sotalol) or bilateral adrenalectomy. A major part of the hind-limb vasodilatation can therefore be attributed to the action of catecholamines released from the adrenal glands. The initial part of the vasodilatation, which still remained after beta-adrenoreceptor blockade and adrenalectomy, was abolished by intravenous injection of guanethidine and phentolamine and seems therefore due simply to withdrawal of vasoconstrictor tone. In confirmation, stimulation of the sympathetic outflow to the hind-quarters after phentolamine and guanethidine had been used to block vasoconstriction did not reveal a sympathetic vasodilator nerve supply to the hind-limb vasculature.     

Coexistence of autonomic and somatic mechanisms in the pressor areas of medulla in cats.

The effects of electrical stimulation and microinjection of sodium glutamate (0.5 M) in the sympathetic pressor areas of the dorsal medulla (DM), ventrolateral medulla (VLM), and parvocellular nucleus (PVC) on the knee jerk, crossed extension, and evoked potential of the L5 ventral root produced by intermittent electrical stimulation were studied in 98 adult cats anesthetized with chloralose and urethane. During electrical and glutamate stimulation of these pressor areas, in addition to the rise of systemic arterial blood pressure marked inhibition of the spinal reflex was produced, indicating presence of neuronal perikarya responsible for these actions. Mild to moderate augmentation of spinal reflexes was also observed during brain stimulation but only in a few cases. The magnitude of the somatic effects among the pressor areas of the VLM, DM, and PVC subsequent to glutamate activation was about the same. Induced spinal reflex inhibition, independent from the baroreceptor and vagal influence, remained essentially unaltered after acute midcollicular decerebration. The inhibition was also observed in cats decerebellated 8-10 days in advance. The inhibition was not affected after bilateral electrolytic- or kainic-acid-induced lesions in the paramedian reticular nucleus (PRN). On the contrary, PRN-induced spinal reflex inhibition was attenuated after bilateral lesions in the DM or VLM. Data suggest that there coexists neuronal subpopulations in the VLM, DM, and PVC that can affect both the sympathetic pressor systems and spinal reflexes.     

Sympathetic activity following paraventricular or ventromedial hypothalamic lesions in rats

The present experiment was designed to measure the sympathetic firing rate of nerve filaments to interscapular brown adipose tissue in rats with acute and chronic lesions in the ventromedial hypothalamus or paraventricular nucleus. Female rats received injections of kainic acid into either the paraventricular nucleus or the ventromedial hypothalamus. The sympathetic activity was measured by recording the firing rate of nerve filaments to interscapular brown adipose tissue after mounting the filaments on silver wire electrodes connected to an amplifier and rate meter. In acute experiments performed 30 minutes after the lesion, the basal firing rate was reduced in both groups and was significantly lower in the VMH-lesioned rats than in those with PVN lesions. In the chronic experiment kainic acid was injected into the VMH or PVN and the sympathetic firing rate was measured 7 to 9 days later. Both lesioned groups gained more weight than controls, but the VMH-lesioned rats gained more weight than the PVN-lesioned rats. The basal firing rate of sympathetic nerve filaments in the VMH-lesioned rats was lower than in the other groups. There was no significant difference in the sympathetic activity between PVN-lesioned and control rats. These experiments support the hypothesis that lesions of the ventromedial hypothalamus reduce the sympathetic activity but that lesions in the paraventricular nucleus do not.     

Potentiation of a cardioinhibitory reflex by hypothalamic stimulation in the rabbit

Repetitive stimulation of an area within the lateral hypothalamus, near the mammillothalamic tract, evoked pressor responses with bradycardia in anaesthetized rabbits. With weak stimulation (cathodal pulses below 75--150 microamperemeter, 1 msec duration, 60--100 per sec for 5--9 sec) the pressor responses were accompanied by bradycardia similar in intensity to that evoked by i.v. administration of noradrenaline. Stronger stimulating currents evoked an intense bradycardia that could not have arisen solely through the baroreceptor reflex. With these stronger currents the heart rate sometimes fell, transiently, to less than 20% of the resting rate. After denervation of the 4 main buffer nerves (sinus and aortic nerves), hypothalamic stimulation could not readily evoke bradycardia, although the pressor, respiratory and other effects remained. When the baroreceptor afferents were activated, either by evoked pressor responses in rabbits whose buffer nerves were intact or by electrical stimulation of the central ends of divided aortic nerves, strong hypothalamic stimulation augmented the bradycardia evoked reflexly from these baroreceptor afferents. This evidence suggests that electrical stimulation of this area in the hypothalamus may facilitate the cardioinhibitory component of the baroreceptor reflex in the rabbit.     

Factors affecting cardiovascular responses to stimulation of hypothalamus in the rat.

Changes in heart rate and arterial pressure to electrical stimulation of 161 histologically verified sites in the hypothalamus and preoptic area were investigated in 60 artificially respired rats under chloralose anesthesia. Stimulation at 80 Hz of most nuclei of the posterior hypothalamus elicited hypertension and bradycardia; stimulation of sites in these nuclei in vagotomized rats elicited hypertension and tachycardia. However, stimulation of the dorsomedial and premamillary nuclei often elicited hypotension and bradycardia; stimulation of these nuclei in vagotomized rats elicited hypertension and tachycardia. Hypertension elicited from the lateral and anterior hypothalamus by 80-Hz stimulation was eliminated or was changed to hypotension during stimulation at 8 Hz. Hypotension and bradycardia elicited from the ventral preoptic area were changed to hypertension and tachycardia after vagotomy; bradycardia, but not hypotension, elicited from the dorsal preoptic area was abolished by vagotomy or methyl atropine administration. Responses elicited from 54 sites in 31 urethan-anesthetized rats were similar to those elicited from vagotomized chloralose-anesthetized rats. These results point to the importance of accurate localization of stimulation sites, stimulation parameters, and anesthetic agents in studies of central neural control of the cardiovascular system.     

Cardiovascular responses elicited by electrical and chemical stimulation of the rostral medullary raphe of the rabbit

Electrical stimulation of the rostral medullary raphe (RMR) of the rabbit elicited pressor responses that were accompanied by tachycardia or bradycardia. Stimulation of dorsal sites (the dorsal raphe obscurus) evoked a pressor/tachycardia response and stimulation of ventral sites (the ventral raphe obscurus, raphe magnus and raphe pallidus) produced a pressor/bradycardia response. Electrical stimulation of the RMR after sinoaortic denervation led to an increase in the magnitude of the pressor response elicited from all stimulation sites, a decrease in the magnitude of the bradycardia produced by stimulation at the ventral sites, but had no effect upon the magnitude of the tachycardia observed from stimulation of the dorsal sites. These findings suggest that electrical stimulation of the dorsal sites leads to inhibition of the cardiomotor component of the baroreceptor reflex. The results of vagal blockade experiments demonstrated that baroreceptor attenuation of the pressor responses at ventral sites was mediated primarily by parasympathetic input to the heart. Chemical stimulation of the RMR with L-glutamate also led to a pressor/tachycardia response at the dorsal sites and a pressor/brachycardia response at the ventral sites. This finding provides evidence that neuronal cell bodies, not axon of passage, mediated the responses elicited by electrical stimulation.     

Cardiovascular role of the major noradrenergic cell groups in the rabbit: analysis based on 6-hydroxydopamine-induced transmitter release

We examined the role of the noradrenergic (NA) neurons of the A1, A2, A1 + A2, A5 and A6 + A7 regions on mean arterial pressure (MAP) and heart rate (HR), by comparing the acute responses of chronically lesioned and sham-operated rabbits to intracisternal 6-hydroxydopamine (6-OHDA, 600 micrograms/kg) which induces central release of transmitter. We studied rabbits (1) with intact arterial baroreceptors (non-denervated) and (2) after sino-aortic denervation (SAD). The acute transmitter release response consisted of an early fall in MAP (observed in SAD rabbits) and a late rise in MAP (observed in both non-denervated and SAD rabbits). Medullary lesions had no effect on either MAP component, but A5 and A6 + A7 lesions attenuated both pressor and depressor responses. Normally the transmitter release-induced MAP responses are modified by baroreceptor feedback. The 6-OHDA-induced HR changes were vagal in non-denervated rabbits and were sympathetically mediated in SAD rabbits. In non-denervated rabbits, A1, A2 and A1 + A2 lesions affected mainly the early vagal component, whilst A6 + A7 lesions affected the late vagal component. In SAD rabbits the early bradycardia was due to sympathetic inhibition and the late tachycardia due to sympathetic excitation; A1 + A2 lesions and A5 lesions attenuated the sympathetic bradycardia. We conclude that the various components of the MAP and HR responses are mediated through distinctive NA pathways; the deficits of a given lesion could be due to either to loss of NA cell bodies or of NA fibers of passage.     

Rotation evoked by nigral stimulation following lateral hypothalamic,striatal, and pallidal lesions in rats

Contraversive rotation evoked by electrical stimulation of the rat substantia nigra (nigral-evoked rotation, NER) was not reduced by 6-hydroxydopamine (6-OHDA, 4 μg in 2 μl or 1 μg in 0.5 μl) at the ipsilateral lateral hypothalamus. These lesions produced striatal dopamine depletions equivalent to those produced by electrolytic lesions at that site which reduced NER. Electrolytic lesions at the lateral hypothalamus produced equivalent reduction in NER in rats with prior microinjection of either 6-OHDA (8 μg in 4 μl) or vehicle at that site. Thus, the decrease in NER after electrolytic lesions at the lateral hypothalamus appears to be entirely due to destruction of nondopaminergic fibers. Small electrolytic lesions at the ipsilateral caudate-putamen did not significantly change NER. Large electrolytic lesions at the caudate-putamen did not alter NER at 2 h after lesion but did reduce it at 3, 7, and 14 days postlesion. Electrolytic lesions at the ipsilateral globus pallidus significantly reduced contraversive NER at all times tested (2, 3, 7, and 14 days after lesion). Some rats with pallidal lesions responded to nigral stimulation with ipsiversive rotation. The difference in time course of the reduction in contraversive NER after caudate-putamen and pallidal lesions suggests that NER might be mediated by antidromic activitation of striatonigral neurons that send axonal collaterals to the pallidum.     

Accelerated norepinephrine turnover in peripheral tissues after ventromedial hypothalamic stimulation in rats

To obtain evidence for a functional connection between the ventromedial hypothalamic nucleus (VMH) and the sympathetic nervous system, effects of electrical stimulation of the VMH, the lateral hypothalamic area (LH) and the paraventricular hypothalamic nucleus (PVN) on norepinephrine (NE) turnover in the heart, liver, pancreas, spleen, submandibular gland and the interscapular brown adipose tissue were examined in anesthetized rats. Stimulation of the VMH elicited a 3-8-fold increase in the rate of NE turnover in all organs examined, whereas stimulation of the LH or the PVN had no appreciable effects. The effect of VMH stimulation was abolished after sympathetic ganglionic blockade with hexamethonium. Epinephrine turnover in the adrenal gland was accelerated by stimulation of not only the VMH but also the LH. It was concluded that the VMH is intimately associated with sympathetic facilitation in peripheral tissues.     

Role of the hypothalamus in insulin-independent glucose uptake in peripheral tissues

To clarify the role of the ventromedial hypothalamus (VMH)-sympathetic nervous system in insulin-independent glucose uptake in peripheral tissues, tissue glucose uptake was assessed in vivo by the 2-[3H]deoxyglucose method during electrical stimulation of the VMH in anesthetized rats. VMH stimulation significantly increased the rate constant of glucose uptake in brown adipose tissue (BAT), heart and skeletal muscles, but not in white adipose tissue and brain. The effect of VMH stimulation on glucose uptake in BAT was abolished by local sympathetic denervation, indicating that the increase in glucose uptake is mediated by the sympathetic nerves. Electrical stimulation of the lateral hypothalamus, on the other hand, had no appreciable effects on 2-[3H]deoxyglucose uptake in any tissues. Changes in glucose transporters after VMH stimulation were also examined by the [3H]cytochalasin B binding method using sarcolemmal membranes isolated from heart muscle. Scatchard analysis of cytochalasin B binding indicated that VMH stimulation did not alter both the number and affinity (dissociation constant) of glucose transporters in the heart sarcolemmal membranes, whereas insulin administration increased the number of transporters in the membranes. These results suggest that the mechanism by which VMH stimulation increases glucose uptake in muscle is different from that of insulin.     

The rostral ventrolateral medulla mediates suppression of the circulatory system by the ventromedial nucleus of the hypothalamus

We recently reported that a train of episodic neural discharges within the ventromedial nucleus of the hypothalamus (VMH) associated with suppression of the circulatory system had been determined by monitoring multiple unit activity (MUA). Abrupt increases in neural activity (MUA volleys; 1 to 4 min in duration) accompanied transient decreases in heart rate (HR) and blood pressure (BP), and showed circadian rhythm, occurring every 15 to 30 min in the light phase but seldom in the dark phase. The present study was aimed to determine if neurons in the vasomotor area of the rostral ventrolateral medulla (RVL) are involved in this VMH-induced cardiovascular suppression. MUAs of the VMH and RVL were monitored simultaneously with HR and BP in urethane-anesthetized rats. In synchrony with each MUA volley in the VMH, spontaneous activity of RVL neurons significantly decreased, as well as HR and BP. These RVL neurons are most likely vasomotor neurons because MUA of the RVL was attenuated by baroreceptor reflex activation, and electrical stimulation of these cells through the MUA recording electrodes produced pressor responses. These data suggest that VMH neurons that show a train of episodic discharges suppress the circulatory system at least in part by inhibiting the excitability of vasomotor neurons in the RVL.