Ventrolateral Medulla Oblongata Research Articles

Inhibition of the A1 area prevents hemorrhage-induced secretion of vasopressin in rats

In rats, secretion of vasopressin initiated by hemorrhage was completely abolished after muscimol-induced inhibition of neuronal function in the A1 region of the ventrolateral medulla oblongata. The A1 neurons are essential links in the central pathway to hypothalamic vasopressin-synthesizing neurons in this species.

A novel mechanism of action for hypertension control: Moxonidine as a selective I1-imidazoline agonist

Sympathoadrenal inhibition by a direct action within the central nervous system is an advantageous route to blood pressure control. Stimulation of brain alpha 2-adrenergic receptors is one mechanism for sympathoadrenal suppression, but comes at the cost of nonspecific depression of CNS function, including sedation and decreased salivary flow. Evidence is accumulating for a second pathway for pharmacological control of sympathoadrenal outflow, mediated by a novel receptor specific for imidazolines. First-generation central antihypertensive agents, which are imidazolines such as clonidine, act primarily to stimulate these I1-imidazoline receptors in the rostral ventrolateral medulla oblongata (RVLM) to lower blood pressure, but have sufficient agonism at alpha 2-adrenergic receptors to produce side effects. Second-generation centrally acting antihypertensive agents, such as moxonidine and rilmenidine, are selective for I1 relative to alpha 2 receptors. The reduced alpha 2 potency of these agents correlates with reduced severity of side effects. In this study we further established the selectivity of moxonidine for I1-imidazoline sites by characterizing the direct interaction of [3H]moxonidine with these receptors in the RVLM and in adrenomedullary chromaffin cells. [3H]Moxonidine preferentially labeled I1-imidazoline sites relative to alpha 2-adrenergic sites, only a small portion of which were labeled in the RVLM. [3H]Moxonidine binding to I1-imidazoline sites was modulated by guanine nucleotides, implying that I1-imidazoline sites may be membrane receptors coupled to guanine nucleotide binding regulatory proteins (G proteins). Receptor autoradiography with [125I]p-iodoclonidine confirmed the presence of I1-imidazoline sites in the RVLM and other areas of the brainstem reticular formation. In contrast, alpha 2-adrenergic sites were mainly localized to the nucleus of the solitary tract. Moxonidine selectively displaced [125I]p-iodoclonidine binding from reticular areas, including the RVLM. In vivo studies in SHR rats confirmed the ability of moxonidine to normalize hypertension by an action within the RVLM and confirmed the correspondence of I1 binding affinity and antihypertensive efficacy. We also discuss prior literature on the cardiovascular pharmacology of imidazolines, reinterpreting previous studies that only considered alpha-adrenergic mechanisms.

Direct projections from the ventrolateral medulla oblongata to the limbic forebrain: anterograde and retrograde tract-tracing studies in the rat.

Neurons in the ventrolateral medulla oblongata, a brain region implicated in central vasomotor regulation, have previously been reported to project to some forebrain limbic structures. The aim of the present study was (1) to describe the termination pattern of ventral medullary afferents in forebrain limbic areas using anterograde tract tracing, and (2) to determine the location and some morphological characteristics of the projection neurons using retrograde tract tracing from selected forebrain sites. Following ionophoretic microinjections of the anterograde tract tracer Phaseolus vulgaris leucoagglutinin into the rostral ventrolateral medulla, labelled afferents were observed in the hippocampus, entorhinal and retrosplenial cortices, dorsal septum, nucleus accumbens, and the medial prefrontal cortex. Anterogradely labelled axons, ascending from the caudal ventrolateral medulla, could be traced only to the rostral aspects of the investigated forebrain limbic structures. Here, the main target of the ascending projection was in the ventral septum. However, labelled terminals were also present in the nucleus accumbens, the dorsolateral septum, and in the infralimbic cortex. The density of the ventrolateral medullary projections into all examined forebrain areas was low. The location of the cells in the ventral medulla oblongata which give rise to direct forebrain projections was examined using retrograde tract tracing with wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP). Following WGA-HRP injections into the septo-accumbens region, retrogradely labelled cells were present in both the rostral and caudal ventrolateral medulla. When the tract tracer injection was restricted to the ventral region of the septal complex, the labelled cells were concentrated in the caudal aspects of the ventrolateral medulla (and the nucleus of the solitary tract). Following tracer injections into the anterior cingulate cortex or the hippocampus or the entorhinal cortex, retrogradely labelled cells in the medulla oblongata were predominantly in the rostral ventrolateral medulla. As a first attempt to reveal the chemical nature of the projection cells, the contribution of tyrosine hydroxylase-immunoreactive cells to the innervation of the septo-accumbens area was also investigated: tyrosine hydroxylase-immunoreactive cells of both the caudal ventrolateral medulla and the nucleus of the solitary tract were found to contribute to the innervation of the septo-accumbens area. The distribution of retrogradely labelled cells as well as the termination pattern of the anterogradely labelled terminals indicated that the innervation of the various forebrain limbic areas arises from cells, diffusely distributed in the rostral and/or the caudal ventrolateral medulla oblongata.(ABSTRACT TRUNCATED AT 400 WORDS)

Close appositions between Tyrosine hydroxylase immunoreactive boutons and respiratory neurons in the rat ventrolateral medulla

The extent of the adrenergic input to respiratory neurons in the ventrolateral medulla oblongata of rats was assessed by using a combination of intracellular recording, dye filling, and immunohistochemistry. Twenty-two neurons that displayed a pronounced respiration-related modulation of their membrane potential, and could not be antidromically activated by electrical stimulation of the superior laryngeal, vagus, or facial nerves, were labelled by intracellular injection of biocytin. Three types of respiration-related neurons were labelled: small neurons located in the Bötzinger complex between 0.5 and 1.0 mm caudal to the facial nucleus; medium-sized neurons located in the ventral respiratory group 1.0 to 2.0 mm caudal to the facial nucleus; and large motoneurons located within the nucleus ambiguus 0.5 to 2.0 mm caudal to the facial nucleus. Small Bötzinger neurons [length = 22 +/- 5 microns, width = 13 +/- 3 microns, area = 222 +/- 79 microns2; (mean +/- SD, n = 5)] had membrane potentials of -15 to -27 mV during the recording period. Four of five of these cells had profuse axonal terminations between 50 microns caudal and 450 microns rostral to their somata, suggesting that they may form part of local networks responsible for generating respiratory activity. Medium-sized ventral respiratory group neurons (length = 26 +/- 5 microns, width = 18 +/- 4 microns, area = 377 +/- 141 microns2; n = 5) were found in the vicinity of the nucleus ambiguus dorsal to the lateral reticular nucleus. Three of five of these neurons had an axon that crossed the midline and travelled caudally. One axon had a collateral with varicosities close to its soma. The somata of motoneurons (length = 29 +/- 6 microns, width = 21 +/- 4 microns, area = 485 +/- 142 microns2; n = 12) were located within the nucleus ambiguus, and had axons that could be traced to exist points from the medulla. Tyrosine hydroxylase immunoreactive cells and their terminal fibres within the medulla were localised by immunocytochemistry. Small Bötzinger neurons received the largest number of close appositions from tyrosine hydroxylase immunoreactive boutons (13 +/- 2 appositions/neuron; n = 5). Medium-sized ventral respiratory group neurons received fewer appositions (8 +/- 4 appositions/neuron; n = 5). Most motoneurons (n = 10) received few appositions from tyrosine hydroxylase immunoreactive boutons, while two received none. The average number was 3 +/- 3 appositions/neuron (n = 12).(ABSTRACT TRUNCATED AT 400 WORDS)

Milk consumption and bone mass

Neuronal metabolic activity was studied by in vivo electrochemistry in two brain areas of the anesthetized rat: the nucleus reticularis lateralis (NRL) region of the ventrolateral medulla oblongata - site of the hypotensive action of clonidine-like imidazolines - and the locus coeruleus (LC), which is involved in the sedative effect of these drugs. Hypotensive doses of i.v. rilmenidine (0.3 and 1.5 mg/kg), which is structurally related to clonidine, induced a dose-related inhibition of the metabolic activity of catecholaminergic neurons in the NRL region whereas higher doses (50-fold) were required to inhibit the activity of the catecholaminergic neurons in the locus coeruleus. On the other hand azepexole, another centrally acting antihypertensive drug that is not structurally related to the imidazolines failed to inhibit the neuronal metabolic activity of the RNL region when administered i.v. in hypotensive doses (1 mg/kg). Taken together, these findings suggest that the central hypotensive action of clonidine-like drugs requires the imidazoline structure or pharmacologically compatible compounds like rilmenidine. Our results also show that rilmenidine is twice as selective as clonidine for the NRL region, which contains imidazoline-preferring receptors, compared with the LC, which contains mainly α2-adrenoceptors. In conclusion, this study provides a functional confirmation of the dissociation between the therapeutic (hypotensive) and untoward (sedative) effects of rilmenidine.

Innervation of serotonergic medullary raphe neurons from cells of the rostral ventrolateral medulla in rats

The Rostral ventral medulla has been shown to consist of three distinct subrogions: the midline or raphéregion, the lateral paragigantocellular-gigantocellular region and the rostro-ventrolateral reticular nucleus. All three regions have been shown to contribute to central vaso-regulation and to project towards sympathetic preganglionic neurons of the thoracic spinal cord. Therefore it is of particular interest to describe the interconnections between the three regions and to see if local afferents reach cells which have been implicated in the regulation of descending inputs. Following injections of the anterograde tract tracer Phaseolus vulgaris leucoagglutinin into the lateral paragigantocellular nucleus or the rostroventrolateral reticular nucleus, labelled axons were traced into the medullary raphénuclei and the contralateral rostral ventrolateral medulla. Efferents originating from both regions innervated the raphépallidus, raphéobscurus and raphémagnus. However the distribution of terminals originating from the two regions was different in the contralateral ventrolateral medulla oblongata. The data indicate that the connection between the ipsi- and contralateral equivalents of both the lateral paragigantocellular-gigantocellular region and the rostroventrolateral reticular nucleus are stronger than the cross-connection between the ipsi- and contralateral parts of the two different regions. In the second part of the study, the existence of direct projections from the rostroventrolateral reticular nucleus and the lateral paragigantocellular-gigantocellular region onto serotonin-immunogold-labelled cells of the ventromedial medulla were investigated. The correlated light and electron microscopic analysis revealed direct synaptic contacts between axons originating from both the lateral paragigantocellular-gigantocellular region and the rostroventrolateral reticular nucleus, and serotonin-immunoreactive cells of the raphéobscurus and raphépallidus. The results of the present light microscopic tract-tracing study revealed a different pattern of the intramedullary projection of the lateral paragigantocellular-gigantocellular region and the rostroventrolateral reticular nucleus. These data are in support of the proposed parcellation of the two cytoarchitectonically different areas of the rostral ventrolateral medulla into two functionally distinct subdivisions. Furthermore, the direct anatomical connection revealed in the present study between cells of the rostral ventrolateral and ventromedial medulla oblongata indicates the possibility that vasoregulatory effects of some cells of the rostral ventrolateral medulla oblongata might be executed via direct projections onto serotonin-immunoreactive cells of the medullary raphénuclei.

Localization of nitric oxide synthase-immunoreactive neurons in the solitary nucleus and ventrolateral medulla oblongata of the rat: their relation to catecholaminergic neurons

The morphological relationship between nitric oxide (NO) and catecholamines in the solitary nucleus (SOL) and ventrolateral medulla oblongata (VLM) was studied by a double immunostaining method with antibodies against NO synthase (NOS), an NO-synthesizing enzyme, and tyrosine hydroxylase (TH), a catecholamine-synthesizing enzyme. Although NOS- and TH-immunoreactive neurons were widely distributed in the SOL and VLM, these immunoreactivities did not coexist in any single neurons. NOS-immunoreactive neurons formed clusters in some restricted regions, i.e. in the medial subnucleus of the SOL, where both NOS- and TH-immunoreactive neurons showed a complementary distribution. These findings suggest that NO-producing neurons constitute a subclass that is distinct from that of catecholaminergic neurons.

Monosynaptic projections from the rostral ventrolateral medulla oblongata to identified sympathetic preganglionic neurons

The rostral ventrolateral medulla oblongata plays an important role in the control of arterial blood pressure and it has strong descending projections into the intermediolateral nucleus of the thoracic spinal cord, where the majority of sympathetic preganglionic neurons are located. The purpose of this study was to see whether these projections form synaptic contacts with sympathetic preganglionic neurons in the rat. Projections from both the lateral part of the rostral ventrolateral medulla (rostroventrolateral reticular nucleus) and from the more medial region (lateral paragigantocellular nucleus) were investigated separately in view of their different functional roles in sympatho-regulation and their different chemical composition. Using anterograde tract-tracing of descending medullary pathways with Phaseolus vulgaris leucoagglutinin and retrograde labelling of sympatho-adrenal preganglionic neurons with cholera B chain conjugated to horseradish peroxidase, the existence of monosynaptic connections was sought by electron microscopy. Synaptic inputs from both the lateral and medial aspects of the rostral ventrolateral medulla oblongata were found on identified sympathetic preganglionic neurons. Synaptic specializations were of both the symmetrical and asymmetrical type. The targets of boutons forming asymmetrical synaptic contacts differed according to their origin: boutons originating from neurons in the rostroventrolateral reticular nucleus were mainly in contact with dendrites of sympathetic preganglionic neurons, while those originating from the lateral paragigantocellular nucleus mainly innervated the cell bodies. Our observations provide anatomical support for the view that there are two distinct classes of sympatho-regulatory cells in the rostral ventrolateral medulla, each of which can directly influence the activity of sympathetic preganglionic neurons; they also emphasize the importance of detailed investigation of the subrogions of the ventrolateral medulla with respect to their sympatho-regulatory functions.

Ultrastructural studies of medullary synaptic inputs to vasopressin-immunoreactive neurons in the supraoptic nucleus of the rat hypothalamus

Direct projections from the A1/C1 catecholaminergic cell group in the caudal ventrolateral medulla oblongata to neurons containing vasopressin (VP) in the supraoptic nucleus (SON) were studied electron microscopically by a double-labeling technique which combines anterograde tracing after injection of wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) into the A1/C1 cell group with VP immunocytochemistry. WGA HRP-labeled axon terminals originating from neurons in the A1/C1 cell group were found to make synaptic contacts with VP-immunoreactive cell bodies and dendrites in the SON, most often forming axo-dendritic synapses. This indicates that VP-containing neurosecretory neurons in the SON receive monosynaptic catecholaminergic input from the A1/C1 cell group.

Contribution of catecholaminergic neurons of the dorsomedial and ventrolateral medulla oblongata to the hypotensive effect of clonidine in spontaneously hypertensive rats: in vivo voltammetric studies.

Our previous electrochemical studies in the normotensive Wistar-Kyoto (WKY) rat showed a positive correlation between the hypotensive effect of low doses of clonidine (2-10 micrograms/kg intravenously) and inhibition of the activity of catecholaminergic neurons within the brainstem, and that this action was mediated by imidazoline-preferring receptors. In the present study the possibility of a relationship between the centrally mediated hypotensive effect of clonidine and the metabolic activity of catecholaminergic neurons of the ventrolateral and dorsomedial medulla oblongata was investigated in pentobarbital-anaesthetized spontaneously hypertensive rats (SHR). Neuronal metabolic activity was monitored by in vivo electrochemistry in the nucleus reticularis lateralis region of the ventrolateral medulla and in the nucleus tractus solitarii region of the dorsomedial medulla oblongata. Hypotensive doses of intravenously administered clonidine (10 micrograms/kg) failed to inhibit the neuronal metabolic activity of the nucleus reticularis lateralis region; fivefold higher doses were required to inhibit these neurons. The low dose of clonidine (10 micrograms/kg) decreased the metabolic activity of the nucleus tractus solitarii region. Nevertheless, this effect did not appear to be correlated with a reduction in blood pressure and it was not attenuated by a prior central injection of idazoxan (5 nmol/kg intracisternally), which almost completely prevented the hypotensive and the neuronal inhibitory effects of clonidine in the nucleus reticularis lateralis region of the normotensive rat. Both the site and the mechanism of the central hypotensive action of clonidine in the SHR appear to be different from those in normotensive control WKY rats.

Characteristics of sympathetic reflexes evoked by electrical stimulation of phrenic nerve afferents

In chloralose-anaesthetized cats, sympathetic reflex responses were recorded in left cardiac and renal nerve during stimulation of afferent fibres in the ipsilateral phrenic nerve. In cardiac nerve, a late reflex potential with a mean onset latency of 75.6 ± 13.8 ms was regularly recorded which, in 20% of the experiments, was preceded by an early, very small reflex component (latency between 35 and 52 ms). In contrast, in renal nerve only a single reflex component after a mean latency of 122.1 ± 13.1 ms was observed. Bilateral microinjections of the GABA-agonist muscimol into the rostral ventrolateral medulla oblongata resulted in a nearly complete abolition of sympathetic background activity and in an 88% reduction of the late reflex amplitude with only small effects on the latency of the evoked potentials. Under this condition, an early reflex component was never observed to appear. After subsequent high cervical spinalization, the residual small potentials which persisted after bilateral muscimol injections were completely abolished and in cardiac nerve an early reflex potential with a mean latency of 45 ± 10 ms was observed in all but one experiment. The early reflex was therefore referred to as a spinal reflex component which, however, is suppressed in most animals with an intact neuraxis. In the renal nerve a spinal response was only observed in one experiment after spinalization. The results suggest that sympathetic reflexes evoked by stimulation of phrenic nerve afferent fibres possess similiar spinal and supraspinal pathways as previously described for somato-sympathetic and viscero-sympathetic reflexes. As described for these reflexes, the spinal component of the phrenico-sympathetic reflex is also under the control of a descending tonic inhibition of supraspinal origin.

Medullary pathways for adrenocorticotropic hormone and vasopressin secretion in rabbits.

We determined, in urethan-anesthetized rabbits, whether pharmacological alteration of neuronal function in the ventrolateral medulla oblongata, including the A1 area, and in the nucleus tractus solitarii (NTS), alters plasma adrenocorticotropic hormone (ACTH) and vasopressin and whether inhibition of neuronal function in the ventrolateral medulla impairs the secretion of ACTH normally observed in response to hemorrhage or constriction of the inferior vena cava. We also tested whether the increase in plasma ACTH and vasopressin after pharmacological inhibition of neuronal function in the NTS is dependent on a pathway that synapses in the A1 area of the ventrolateral medulla. Activation of the A1 area with bicuculline increased both ACTH and vasopressin. Inhibition of the NTS with muscimol increased levels of both hormones, as did hemorrhage and constriction of the inferior vena cava. Inhibition of neuronal function within the A1 area with muscimol eliminated the secretion of vasopressin but did not significantly alter the secretion of ACTH, obtained by injecting muscimol into the NTS. Injection of muscimol into the A1 area eliminated the secretion of both ACTH and vasopressin in response to constriction of the inferior vena cava and, in the case of vasopressin, in response to hemorrhage. Although hemorrhage-initiated secretion of ACTH was significantly reduced by injection of muscimol into the A1 area, it was not completely eliminated by these injections or by injections of muscimol into a more rostrocaudally extensive region of the medulla oblongata. We conclude that the net output from the NTS tonically inhibits secretion of both ACTH and vasopressin, reflecting tonic baroreceptor tone. For vasopressin, the pathway from the NTS to the hypothalamus is dependent on a synapse in the A1 area. For ACTH, there are pathways to the hypothalamus that do not synapse in the A1 area, but neurons in this region do have an excitatory effect on secretion of ACTH.

Expression of Fos-like immunoreactivity by yohimbine and clonidine in the rat brain

To elucidate the role of α 2-adrenoceptors in transcriptional control in the rat brain, we localized the Fos-like immunoreactivity (Fos-LI) induced by α 2-adrenoceptor agonists and by an antagonist. Injections of yohimbine (5 mg/kg, i.p.) into rats led to the induction of Fos-LI in areas with a dense α 2-adrenoceptor binding such as the locus coeruleus, the bed nucleus of stria terminalis, the central nucleus of amygdaloid complex, the paraventricular nucleus, the nucleus tractus solitarius, and ventrolateral medulla oblongata. Clonidine (500 μg/kg, i.p.) suppressed the Fos expression by yohimbine in these nuclei, and clonidine (100 μg/kg, i.p.) or guanabenz (4 mg/kg, i.p.) induced Fos-LI in oxytocin neurons in the paraventricular and supraoptic nuclei in the hypothalamus. Thus, the α 2-adrenoceptor is involved in transcriptional control via Fos expression in neurons related to autonomic and other functions.

Imidazole receptors and clonidine-displacing substance in relationship to control of blood pressure, neuroprotection, and adrenomedullary secretion.

Clonidine, idazoxan, rilmenidine, and comparable agents bind to imidazol(in)e (IR), as well as alpha 2-adrenergic, receptors. Interaction with IRs mediates the hypotension elicited by these drugs at their site of action in the rostral ventrolateral medulla oblongata (RVL) and probably the neuroprotection in focal ischemic cerebral infarction. Unlike alpha 2-adrenergic receptors, IRs are not coupled to G-proteins. Their native ligand may be clonidine-displacing substance (CDS), a potent, partially purified adrenomedullary secretagogue, distributed regionally in brain and some peripheral organs. IRs and CDS may be important in the genesis, expression, and/or therapy of hypertension and stroke.

Localization of nitric oxide synthase immunoreactive neurons in the solitary nucleus and ventrolateral medulla oblongata of the rat

Localization of nitric oxide synthase immunoreactive neurons in the solitary nucleus and ventrolateral medulla oblongata of the rat

Selectivity of rilmenidine for the nucleus reticularis lateralis, a ventrolateral medullary structure containing imidazoline-preferring receptors

Neuronal metabolic activity was studied by in vivo electrochemistry in two brain areas of the anesthetized rat: the nucleus reticularis lateralis (NRL) region of the ventrolateral medulla oblongata - site of the hypotensive action of clonidine-like imidazolines - and the locus coeruleus (LC), which is involved in the sedative effect of these drugs. Hypotensive doses of i.v. rilmenidine (0.3 and 1.5 mg/kg), which is structurally related to clonidine, induced a dose-related inhibition of the metabolic activity of catecholaminergic neurons in the NRL region whereas higher doses (50-fold) were required to inhibit the activity of the catecholaminergic neurons in the locus coeruleus. On the other hand azepexole, another centrally acting antihypertensive drug that is not structurally related to the imidazolines failed to inhibit the neuronal metabolic activity of the RNL region when administered i.v. in hypotensive doses (1 mg/kg). Taken together, these findings suggest that the central hypotensive action of clonidine-like drugs requires the imidazoline structure or pharmacologically compatible compounds like rilmenidine. Our results also show that rilmenidine is twice as selective as clonidine for the NRL region, which contains imidazoline-preferring receptors, compared with the LC, which contains mainly α 2-adrenoceptors. In conclusion, this study provides a functional confirmation of the dissociation between the therapeutic (hypotensive) and untoward (sedative) effects of rilmenidine.

Transneuronal labeling of neurons in rabbit brain after injection of herpes simplex virus type 1 into the aortic depressor nerve

Herpes simplex virus type 1 (HSV1) was injected into either the aortic depressor nerve or the vagus nerve in the rabbit. Four or 5 days after injection of virus, the rabbit brain was processed immunohistochemically to demonstrate viral antigen. After injection into the aortic nerve HSV1 positive cells were found principally ipsilaterally within the nucleus tractus solitarius, area postrema, caudal and rostral ventrolateral medulla oblongata, the spinal trigeminal complex, raphe nuclei, A5 area, locus coeruleus, parabrachial nucleus, periaqueductal gray, ventrolateral hypothalamic area, paraventricular nucleus, amygdala, bed nucleus of the stria terminalis and insular cortex. Double labeling studies indicated that approximately 85% of the virus-containing neurons in the ventrolateral medulla, and virtually all the HSV-positive neurons in the A5 area and locus coeruleus also contained tyrosine hydroxylase. In the raphe nuclei and parapyramidal region approximately 33% of virus-containing cells reacted positively with PH8 antibody, a marker for serotonin synthesis. After injection of HSV1 into the vagus nerve labeled cells were found in similar brain areas, with a more bilateral distribution. The HSV - positive neurons may be involved in the processing of baroreceptor-derived information.

Antagonistic effects of somatostatin and substance P on respiratory regulation in the rat ventrolateral medulla oblongata

Substance P (SP) in the dose range 0.75–1.5 nmol exerts a potent stimulatory effect on ventilation after microinjection into the rat ventrolateral medulla oblongata (VLM; n. reticularis lateralis, n. paragigantocellularis lateralis). A significant but less pronounced effect is also seen in the dorsal medulla (DM; n. tractus solitarius). Somatostatin (0.6–1.8 nmol) inhibited ventilation and induced apnoea after microinjection into the VLM but not the DM. Serial microinjections of the two peptides showed a reciprocal antagonistic action in the VLM but not in the DM. The apnoea-inducing effect of SOM was blunted by SP while SOM reduced the ventilatory stimulation induced by SP. Extracellular single unit recordings were performed following the microiontophoretic application of SP and/or SOM to respiratory-related and non-respiratory-related neurons in the VLM and DM. Although a heterogeneous population of neurons were recorded from, the majority of respiratory-related units in the VLM responded with excitation to SP and inhibitory to SOM. A direct interaction between the peptides was seen in some respiratory-related units. The neurons not responding to either of the peptides were usually non-respiratory. Dorsal to the VLM, the type of response to the two peptides was less likely to be antagonistic and a wider distribution of response types were recorded. The results indicate a direct physiological antagonism between SP and SOM regarding their effects on respiratory regulation elicited in the VLM.

Effects of depleting central and peripheral adrenaline stores on blood pressure in stroke-prone spontaneously hypertensive rats

The potential role of adrenaline, both circulating and in the central nervous system, in the maintenance of high blood pressure was examined in stroke-prone spontaneously hypertensive rats (SHRSP). α-Monofluoromethyldopa, a long-lasting inhibitor of dopa decarboxylase, was used to induce rapid depletion of central and peripheral catecholamine stores. Subsequent inhibition of phenylethanolamine- N-methyltransferase (PNMT) allowed the gradual restoration of dopamine and noradrenaline but not adrenaline, resulting in a greater relative depletion of adrenaline. Adrenaline was almost totally depleted in the circulation and peripheral tissues. The resting level of blood pressure, however, was unaffected, excepting after administration of a vasopressin (AVP) antagonist. Moreover, there was no reduction in the magnitude of acute pressor responses to electrical stimulation of the rostral ventrolateral medulla oblongata (C1 area), despite extensive loss of adrenaline from the brainstem and spinal cord. The results suggest that adrenaline contributes to the resting level of blood pressure but that its loss can be offset by the pressor activity of AVP. Thus neither central nor peripheral adrenaline stores appéar to be essential for the maintenance of hypertension or for centrally-evoked vasoconstriction in adult SHRSP.

Inhibitory Vasomotor Neurons in the Caudal Ventrolateral Medulla Oblongata

Tonically active, probably GABAergic, neurons in the caudal ventrolateral medulla oblongata decrease sympathetic vasomotor tone by directly inhibiting sympathoexcitatory premotor neurons in the rostral medulla. These caudal inhibitory vasomotor neurons may constitute the inhibitory link in the central baroreceptor-vasomotor pathway.