Domain-specific distribution of gap junctions defines cellular coupling to establish a vascular relay in the retina.

In the retina, diverse functions of neuronal gap junctions (GJs) have been established. However, the distribution and function of vascular GJs are less clear. Here in the mouse retina whole mounts, we combined structural immunohistochemical analysis and a functional assessment of cellular coupling with a GJ-permeable tracer Neurobiotin to determine distribution patterns of three major vascular connexins. We found that Cx43 was expressed in punctate fashion on astroglia, surrounding all types of blood vessels and in continuous string-like structures along endothelial cell contacts in specialized regions of the vascular tree. Specifically, these Cx43-positive strings originated at the finest capillaries and extended toward the feeding artery. As this structural arrangement promoted strong and exclusive coupling of pericytes and endothelial cells along the corresponding branch, we termed this region a "vascular relay." Cx40 expression was found predominantly along the endothelial cell contacts of the primary arteries and did not overlap with Cx43-positive strings. At their occupied territories, Cx43 and Cx40 clustered with tight junctions and, to a lesser extent, with adhesion contacts, both key elements of the blood-retina barrier. Finally, Cx37 puncta were associated with the entire surface of both mural and endothelial cells across all regions of the vascular tree. This combinatorial analysis of vascular connexins and identification of the vascular relay region will serve as a structural foundation for future studies of neurovascular signaling in health and disease.

[A COMPARATIVE STUDY OF CATECHOLAMINERGIC AND NITROXIDERGIC VASOMOTOR NEURONS IN THE NUCLEI OF THE CAUDAL PART OF THE BRAINSTEM OF THE RAT].

Immunohistochemical methods for the demonstration of tyrosine hydrolase (TH) and neuronal form of nitric oxide synthase (nNOS) were used to study the distribution of catecholaminergic and nitroxidergic vasomotor neurons respectively, in the nuclei of the medulla oblongata and the pons of 12 Wistar rats. Most often the expression of TG was found in neurons located in the nucleus and several reticular nuclei (gigantocellular, paragigantocellular, caudal pons nucleus), but the proportion of immunoreactive neurons did not exceed 8-14%. In the other nuclei (reticular parvocellular nucleus and oral pons nucleus, spinal nucleus of the trigeminal nerve) the value of this parameter ranged from 1 to 3%. In a large group of nuclei with proven vasomotor function such neurons were constantly not detected. In the structures with high content of catecholaminergic neurons, nNOS-positive cells were found, as a rule, in fewer numbers than in the nuclei with a limited number of TH-positive neurons.

Vasomotor sympathetic neurons are more excitable than secretomotor sympathetic neurons in bullfrog paravertebral ganglia.

We compared the excitability of secretomotor B and vasomotor C neurons using virtual nicotinic synapses implemented with the dynamic clamp technique. In response to fast synaptic conductance (g(syn)) waveforms modeled after B cell synaptic currents, it took 17.1+/-1.2nS to elicit spikes in 104 B cells and 3.3+/-0.3nS in 35 C cells. After normalizing for whole-cell capacitance, C cells were still more excitable than B cells (76+/-5pS/pF vs. 169+/-8pS/pF). Stimulating C cells with slower g(syn) waveforms, identical to synaptic currents in C cells, further accentuated the difference between cell types. The phenotypic excitability difference did not correlate with time in culture (1-12days) and could not be explained by resting potential (B cells: -65.6+/-0.9mV, C cells: -63.1+/-1.6mV) or input conductance density, which was greater in C cells (24.4+/-4.3pS/pF) than B cells (14.5+/-1.5pS/pF). Action potentials elicited by virtual EPSPs had a threshold voltage for firing that was -28.4+/-0.7mV in C cells and -19.7+/-0.4mV B cells, and an upstroke velocity and peak spike potential that were greater in B cells. The repetitive firing properties of B and C cells were similar; 69-78% phasic, 11-16% adapting and 11-15% tonic. We propose that B and C neurons express different types of Na(+) channels that shape how they integrate nicotinic synaptic potentials.

NO-positive neurons in some nuclei of human bulbar vasomotor center in arterial hypertension.

The distribution of nitroxidergic neurons and activities of neuronal NO synthase in them in some nuclei of the bulbar vasomotor center were studied in patients with early forms of arterial hypertension. Activity of neuronal NO synthase is reduced significantly in the majority of nuclei in patients with early forms of arterial hypertension, while the content of NO-positive cells was only slightly changed. More pronounced changes in this parameter were detected in the solitary tract nuclei in comparison with the reticular formation nuclei, which had efferent relationships with the intermediate lateral spinal nucleus.

Antiphase oscillations of endothelium and smooth muscle [Ca2+]i in vasomotion of rat mesenteric small arteries.

The mechanisms leading to vasomotion in the presence of noradrenaline and inhibitors of the sarcoplasmic/endoplasmic reticulum calcium ATPase were investigated in isolated rat mesenteric small arteries. Isobaric diameter and isometric force were measured together with membrane potential in endothelial cells and smooth muscle cells (SMC). Calcium in the endothelial cells and SMC was imaged with confocal microscopy. In the presence of noradrenaline and cyclopiazonic acid, ryanodine-insensitive oscillations in tone were produced. The frequency was about 1 min(-1) and amplitude about 70% of the maximal tone. The amplitude was reduced by indomethacin and increased with L-NAME. Vasomotion was inhibited by nifedipine and by 40 mM potassium. The frequency was increased and amplitude decreased by removal of the endothelium and by application of charybdotoxin and apamin. The vasomotion was associated with in-phase oscillations of membrane potential in endothelial cells and SMC and oscillations of [Ca2+]i that were in near anti-phase. We suggest a working model for the generation of oscillation based on a membrane oscillator where ion channels in both endothelial cells and SMC interact via a current running between the two cell types through myoendothelial gap junctions, which sets up a near anti-phase oscillation of [Ca2+]i in the two cell types.

Independent vasomotor control of rat tail and proximal hairy skin.

Quantitative differences are known to exist between the vasomotor control of hairy and hairless skin, but it is unknown whether they are regulated by common central mechanisms. We made simultaneous recordings from sympathetic cutaneous vasoconstrictor (CVC-type) fibres supplying back skin (hairy) and tail (hairless) in urethane-anaesthetized, artificially ventilated rats. The animal's trunk was shaved and encased in a water-perfused jacket. Both tail and back skin CVC-type fibres were activated by cooling the trunk skin, and independently by the resultant fall in core (rectal) temperature, but their thresholds for activation differed (skin temperatures 38.8 +/- 0.4 degrees C versus 36.8 +/- 0.4 degrees C, core temperatures 38.1 +/- 0.2 degrees C versus 36.8 +/- 0.2 degrees C, respectively; P < 0.01). Back skin CVC-type fibres were more responsive to skin than to core cooling, while the reverse applied to tail fibres. Back skin CVC-type fibres were less responsive than tail fibres to prostaglandin E2 (PGE2) microinjected into the preoptic area. Spectral analysis showed no significant coherence between tail and back skin CVC-type fibre activities during cooling. After preoptic PGE2 injection, a coherent peak at 1 Hz appeared in some animals; this disappeared after partialization with respect to ventilatory pressure, indicating that it was attributable to common ventilatory modulation. Neuronal inhibition in the rostral medullary raphé by microinjected muscimol (2 mM, 60-120 nl) suppressed both tail and back skin CVC-type fibre activities, and prevented their responses to subsequent skin cooling. These results indicate that thermoregulatory responses of hairless and hairy skin vessels are controlled by independent neural pathways, although both depend on synaptic relays in the medullary raphé.

Neurogenic regulation of cochlear blood flow occurs along the basilar artery, the anterior inferior cerebellar artery and at branch points of the spiral modiolar artery.

The cochlea receives its main blood supply from the basilar artery via the anterior inferior cerebellar artery and the spiral modiolar artery. Morphologic studies have shown sympathetic innervation along the spiral modiolar artery of the gerbil and the guinea pig and functional studies in the isolated in vitro superfused spiral modiolar artery of the gerbil have demonstrated norepinephrine-induced vasoconstrictions via alpha(1A)-adrenergic receptors. It is current unclear whether the sympathetic innervation is physiologically relevant. Stimulation of sympathetic ganglia in guinea pigs has been shown to alter cochlear blood flow in situ. Whether these changes originated from local or more systemic changes in the vascular diameter remained uncertain. The goal of the present study was to demonstrate the presence or absence of neurogenic changes in the diameter of the isolated in vitro superfused spiral modiolar artery, anterior inferior cerebellar artery and basilar artery from the gerbil and the guinea pig. Vascular diameter was monitored by videomicroscopy. Electric field stimulation was used to elicit neurotransmitter release. A reversible inhibitory effect of 10(-6) M tetrodotoxin was taken as criterion to discriminate between neurogenic and myogenic changes in vascular diameter. Mesentery arteries of comparable diameter, which are known to respond with a neurogenic vasoconstriction to electric field stimulation, served as controls. Basilar artery, anterior inferior cerebellar artery, spiral modiolar artery and mesentery arteries constricted in response to electric field stimulation. No dilations were observed. Myogenic and neurogenic vasoconstrictions were observed in all vessels. These observations suggest that the sympathetic innervation of the basilar artery, the anterior inferior cerebellar artery and branch points of the spiral modiolar artery is involved in a physiologically relevant control of the vascular diameter in the gerbil and the guinea pig.

Function of interstitial cells of Cajal in the rabbit portal vein.

Interstitial cells of Cajal (ICCs) were identified in the intact fixed media of the rabbit portal vein (RPV) using c-kit staining. The following experiments were performed using single cell preparations of the enzyme-dispersed vessel. Surviving contacts between the processes of single ICCs and the bodies of smooth muscle cells (SMCs) were observed in electron micrographs and by confocal microscopy. Spontaneous rhythmical [Ca2+]i oscillations were observed in ICCs after loading with the calcium indicator fluo-3 and were associated with depolarizations of the ICCs recorded by tight-seal patch pipette. To investigate signal transmission from ICCs to SMCs in dispersed cell pairs, or within small surviving fragments of the ICC network, an ICC was stimulated under voltage-clamp, while changes in [Ca2+]i in the stimulated cell as well as in a closely adjacent SMC or ICCs were monitored using fast x-y confocal imaging of fluo-3 fluorescence. After stimulation of single voltage-clamped ICC by a depolarizing step similar in duration to depolarizations associated with spontaneous [Ca2+]i oscillations, a depolarization and transient elevation of [Ca2+]i was observed in a closely adjacent SMCs after a delay of up to 4 seconds. In contrast, signal transmission from ICC to ICC was much faster, the delay being less than 200 ms. These results suggest that the an ICC may, in addition to generating an electrical signal (such as a slow wave) and thereby acting as a pacemaker for vascular SMCs of RPV, also release some unknown diffusible substance, which depolarizes the SMCs.

Cocaine- and amphetamine-regulated transcript in catecholamine and noncatecholamine presympathetic vasomotor neurons of rat rostral ventrolateral medulla.

Presympathetic vasomotor adrenergic (C1) and nonadrenergic (non-C1) neurons in the rostral ventrolateral medulla (RVLM) provide the main excitatory drive to cardiovascular sympathetic preganglionic neurons in the spinal cord. C1 and non-C1 neurons contain cocaine- and amphetamine-regulated transcript (CART), suggesting that CART may be a common marker for RVLM presympathetic neurons. To test this hypothesis, we first used double-immunofluorescence staining for CART and tyrosine hydroxylase (TH) to quantify CART-immunoreactive (-IR) catecholamine and noncatecholamine neurons in the C1 region. Next, we quantified the proportion of CART-IR RVLM neurons that expressed Fos in response to a hypotensive stimulus, using peroxidase immunohistochemistry for Fos and dual immunofluorescence for CART and TH. Finally, we fluorescently detected CART immunoreactivity in electrophysiologically identified, juxtacellularly labeled RVLM presympathetic neurons. In the RVLM, 97% of TH-IR neurons were CART-IR, and 74% of CART-IR neurons were TH-IR. Nitroprusside infusion significantly increased the number of Fos-IR RVLM neurons compared with saline controls. In nitroprusside-treated rats, virtually all Fos/TH neurons in the RVLM were immunoreactive for CART (98% +/- 1.3%, SD; n = 7), whereas 29% +/- 8.3% of CART-positive, TH-negative neurons showed Fos immunoreactivity. Six fast (2.8-5.8 m/second, noncatecholamine)-, two intermediate (2.1 and 2.2 m/second)-, and five slow (<1 m/second, catecholamine)-conducting RVLM presympathetic vasomotor neurons were juxtacellularly labeled. After fluorescent detection of CART and biotinamide, all 13 neurons were found to be CART-IR. These results suggest that, in rat RVLM, all catecholamine and noncatecholamine presympathetic vasomotor neurons contain CART.

Chemical stimulation of vagal afferent neurons and sympathetic vasomotor tone.

Vagal afferents innervate a diverse range of structures of the thoracic and abdominal viscera. While a proportion of these afferents function as mechanoreceptors and respond to changes in intramural tension within the structures that they innervate, many also sense a broad range of chemical substances ranging from peptides, sugars and lipids present in the intraluminal contents of the gastrointestinal tract, as well as tissue prostanoids, cytokines and monoamines in the cardiopulmonary circulation. This review examines the effects of chemical stimulation of vagal afferents on circulatory and sympathetic vasomotor function. Notably, the von Bezold-Jarisch reflex is a cardiorespiratory reflex produced by chemical activation of cardiopulmonary vagal afferents. Classical stimulants of the von Bezold-Jarisch reflex include the Veratrum alkaloids and 5-HT(3) receptor agonists. Atrial natriuretic peptides are agents which also produce a von Bezold-Jarisch reflex-like response or a sensitisation of this reflex via an action on vagal afferents. Cholecystokinin (CCK) activates abdominal visceral vagal afferents, which apart from a clear role in mediation of satiety, also produces selective sympathetic vasomotor inhibition probably by inhibition of sub-groups of presympathetic vasomotor neurons of the rostral ventrolateral medulla. These actions of CCK may constitute a novel gastrointestinal-cardiovascular reflex. The afferent vagus transmits a diverse array of signals to the central nervous system, influencing sympathetic vasomotor and cardiomotor function, gastrointestinal function, neuroimmune function and endocrine function.

Role of angiotensin II receptors in the regulation of vasomotor neurons in the ventrolateral medulla.

1. There is a high density of angiotensin type 1 (AT1) receptors in various brain regions involved in cardiovascular regulation. The present review will focus on the role of AT1 receptors in regulating the activity of sympathetic premotor neurons in the rostral part of the ventrolateral medulla (VLM), which are known to play a pivotal role in the tonic and phasic regulation of sympathetic vasomotor activity and arterial pressure. 2. Microinjection of angiotensin (Ang) II into the rostral VLM (RVLM) results in an increase in arterial pressure and sympathetic vasomotor activity. These effects are blocked by prior application of losartan, a selective AT1 receptor antagonist, indicating that they are mediated by AT1 receptors. However, microinjection of AngII into the RVLM has no detectable effect on respiratory activity, indicating that AT1 receptors are selectively or even exclusively associated with vasomotor neurons in this region. 3. Under normal conditions in anaesthetized animals, AT1 receptors do not appear to contribute significantly to the generation of resting tonic activity in RVLM sympathoexcitatory neurons. However, recent studies suggest that they contribute significantly to the tonic activity of these neurons under certain conditions, such as salt deprivation or heart failure, or in spontaneously hypertensive or genetically modified rats in which the endogenous levels of AngII are increased or in which AT1 receptors are upregulated. 4. Recent evidence also indicates that AT1 receptors play an important role in mediating phasic excitatory inputs to RVLM sympathoexcitatory neurons in response to activation of some neurons within the hypothalamic paraventricular nucleus. The physiological conditions that lead to activation of these AT1 receptor-mediated inputs are unknown. Further studies are also required to determine the cellular mechanisms of action of AngII in the RVLM and its interactions with other neurotransmitters in that region.

Role of perivascular sympathetic nerves and regional differences in the features of sympathetic innervation of the vascular system.

Maintenance of blood pressure is mostly dependent on sympathetic "tone", and the sympathetic nerve innervates the entire vascular bed, excepting the capillaries. Although norepinephrine (NE) is the principal neurotransmitter released upon sympathetic nerve stimulation, neuropeptide Y and ATP are cotransmitters in various vascular tissues. In addition, dopamine and epinephrine, as well as acetylcholine, have been shown to be sympathetic neurotransmitters in specific vasculatures. Transmitter NE release is modified by a number of endogenous substances including the transmitter itself. Chronic denervation of the preganglionic fiber induces an increase in NE release per pulse, indicating postganglionic neuronal supersensitivity. So far, three main adrenoceptor types have been shown, alpha1, alpha2 and beta, each of which is further divided into at least three subtypes, as well as the alpha1L-adrenoceptor, a phenotype of the cloned alpha1a-adrenoceptor, in the blood vessel. Thus, the response of vessels with different receptor types to a transmitter varies quantitatively and even qualitatively from one vessel to another. The remarkable diversity in the sympathetic innervation mechanism in the vascular system may play an important role in regional variations in the regulation of blood flow. The sympathetic nerve also exerts long-term trophic action on the blood vessel. In conclusion, the sympathetic nervous system plays an important role not only in the regulation of cardiovascular dynamics but in the maintenance of the vessel structure, as well.

Vesicular glutamate transporter DNPI/VGLUT2 is expressed by both C1 adrenergic and nonaminergic presympathetic vasomotor neurons of the rat medulla.

The main source of excitatory drive to the sympathetic preganglionic neurons that control blood pressure is from neurons located in the rostral ventrolateral medulla (RVLM). This monosynaptic input includes adrenergic (C1), peptidergic, and noncatecholaminergic neurons. Some of the cells in this pathway are suspected to be glutamatergic, but conclusive evidence is lacking. In the present study we sought to determine whether these presympathetic neurons express the vesicular glutamate transporter BNPI/VGLUT1 or the closely related gene DNPI, the rat homolog of the mouse vesicular glutamate transporter VGLUT2. Both BNPI/VGLUT1 and DNPI/VGLUT2 mRNAs were detected in the medulla oblongata by in situ hybridization, but only DNPI/VGLUT2 mRNA was present in the RVLM. Moreover, BNPI immunoreactivity was absent from the thoracic spinal cord lateral horn. DNPI/VGLUT2 mRNA was present in many medullary cells retrogradely labeled with Fluoro-Gold from the spinal cord (T2; four rats). Within the RVLM, 79% of the bulbospinal C1 cells contained DNPI/VGLUT2 mRNA. Bulbospinal noradrenergic A5 neurons did not contain DNPI/VGLUT2 mRNA. The RVLM of six unanesthetized rats subjected to 2 hours of hydralazine-induced hypotension contained tenfold more c-Fos-ir DNPI/VGLUT2 neurons than that of six saline-treated controls. c-Fos-ir DNPI/VGLUT2 neurons included C1 and non-C1 neurons (3:2 ratio). In seven barbiturate-anesthetized rats, 16 vasomotor presympathetic neurons were filled with biotinamide and analyzed for the presence of tyrosine hydroxylase immunoreactivity and/or DNPI/VGLUT2 mRNA. Biotinamide-labeled neurons included C1 and non-C1 cells. Most non-C1 (9/10) and C1 presympathetic cells (5/6) contained DNPI/VGLUT2 mRNA. In conclusion, DNPI/VGLUT2 is expressed by most blood pressure-regulating presympathetic cells of the RVLM. The data suggest that these neurons may be glutamatergic and that the C1 adrenergic phenotype is one of several secondary phenotypes that are differentially expressed by subgroups of these cells.

K(+) channel inhibition, calcium signaling, and vasomotor tone in canine pulmonary artery smooth muscle.

We investigated the role of K(+) channels in the regulation of baseline intracellular free Ca(2+) concentration ([Ca(2+)](i)), alpha-adrenoreceptor-mediated Ca(2+) signaling, and capacitative Ca(2+) entry in pulmonary artery smooth muscle cells (PASMCs). Inhibition of voltage-gated K(+) channels with 4-aminopyridine (4-AP) increased the membrane potential and the resting [Ca(2+)](i) but attenuated the amplitude and frequency of the [Ca(2+)](i) oscillations induced by the alpha-agonist phenylephrine (PE). Inhibition of Ca(2+)-activated K(+) channels (with charybdotoxin) and inhibition (with glibenclamide) or activation of ATP-sensitive K(+) channels (with lemakalim) had no effect on resting [Ca(2+)](i) or PE-induced [Ca(2+)](i) oscillations. Thapsigargin was used to deplete sarcoplasmic reticulum Ca(2+) stores in the absence of extracellular Ca(2+). Under these conditions, 4-AP attenuated the peak and sustained components of capacitative Ca(2+) entry, which was observed when extracellular Ca(2+) was restored. Capacitative Ca(2+) entry was unaffected by charybdotoxin, glibenclamide, or lemakalim. In isolated pulmonary arterial rings, 4-AP increased resting tension and caused a leftward shift in the KCl dose-response curve. In contrast, 4-AP decreased PE-induced contraction, causing a rightward shift in the PE dose-response curve. These results indicate that voltage-gated K(+) channel inhibition increases resting [Ca(2+)](i) and tone in PASMCs but attenuates the response to PE, likely via inhibition of capacitative Ca(2+) entry.

Cutaneous vascular bed is not involved in arterial pressure changes elicited by increasing or decreasing the activity of inhibitory vasomotor neurons in caudal ventrolateral medulla in rabbits.

We determined whether caudal ventrolateral medulla (CVLM) vasodepressor neurons tonically inhibit vasomotor tone in the ear in anesthetized rabbits. Injection of L-glutamate (10 nmol in 100 nl) into the CVLM decreased arterial pressure and increased superior mesenteric conductance. Ear conductance decreased (0.43+/-0.06 to 0. 33+/-0.05 cm s(-1) per mmHg, n=15 injections, 12 rabbits, P<0.01). Conversely, bilateral injection of gamma-aminobutyric acid (100 nmol in 100 nl) increased arterial pressure and decreased superior mesenteric conductance. At the same time ear conductance increased (0.39+/-09 to 0.48+/-0.27 cm s(-1) per mmHg, n=8 injections, eight rabbits, P<0.05). Results suggest that ear vessels are not tonically inhibited by the CVLM vasodepressor neurons. Presympathetic motoneurons regulating cutaneous flow may be excited, rather than inhibited, by the CVLM neurons.

Morphological distinction between vasodilator and secretomotor neurons in the pterygopalatine ganglion of the cat.

We investigated whether vasodilator and secretomotor ganglion neurons are morphologically distinguishable from each other in the parasympathetic ganglion of the cat. When Cholera toxin B subunit, a retrograde tracer, was injected into the palatine gland, both large and small ganglion neurons were retrogradely labeled in the pterygopalatine ganglion. On the other hand, when the tracer was injected into gland-free areas (the upper gingiva or epidural space), all neurons labeled in the ganglion were small in size. Thus, it was assumed that small and large neurons labeled in the ganglion represented, respectively, vasomotor and secretomotor and neurons [corrected].

Influence of the hypothalamic paraventricular nucleus on cardiovascular neurones in the rostral ventrolateral medulla of the rat.

1. The question of whether neurones in the paraventricular nucleus (PVN) of the hypothalamus have an excitatory influence on reticulo-spinal vasomotor neurones of the rostral ventrolateral medulla (RVL) has been addressed in this study using anaesthetized rats. 2. Extracellular microelectrode recordings were made from sixty vasomotor neurones in the RVL, identified by their cardiac cycle-related probability of discharge, by the decrease in activity in response to an increase in arterial blood pressure produced by intravenous phenylephrine and by the increase in activity in response to a decrease in blood pressure produced by intravenous nitroprusside. 3. More than 70 % of these RVL vasomotor neurones were identified as spinally projecting by antidromically activating their axons via a stimulating electrode in the lateral funiculus of the T2 or T10 segment of spinal cord. 4. Activation of neurones at different sites in the PVN with a microinjection of d,l-homocysteic acid (DLH) elicited either pressor or depressor responses. 5. At PVN pressor sites fifteen RVL vasomotor neurones were shown to be activated prior to the blood pressure change. A further twenty RVL vasomotor neurones were observed to decrease activity following the blood pressure rise. At PVN depressor sites twelve RVL neurones were inhibited prior to the blood pressure change whereas another thirteen identified RVL neurones increased their discharge following the fall in blood pressure. 6. In three rats single shock electrical stimulation at a PVN pressor site, first identified with DLH, elicited a single or double action potential in thirteen RVL neurones with a latency of 27 +/- 1 ms. 7. It is concluded that PVN neurones may elicit increases in blood pressure via excitatory connections with RVL-spinal vasomotor neurones, and that other PVN neurones may elicit decreases in blood pressure via inhibitory connections with these RVL neurones.

The supply of vasomotor drive to individual classes of sympathetic neuron.

The vasoconstrictor supplies to different tissues show distinct patterns of ongoing and reflex activity, indicating that they are driven by distinct central pathways. Vasomotor tone depends heavily on connections from the brainstem, so class-specific vasomotor drives have been sought amongst the sympathetic premotor neurons which provide those connections. Premotor neurons of the rostral ventrolateral medulla (subretrofacial nucleus) provide most descending vasomotor drive. Together, they drive the sympathetic supplies to heart, blood vessels and adrenal, but not 'non-cardiovascular' sympathetic responses (sweating, pupil dilatation, piloerection, etc.). Individually, they provide preferential or selective drives to particular classes of 'cardiovascular' sympathetic outflow. Subretrofacial neurons are arranged topographically, forming a neural map of the functional class (target tissue), not the body region, of the driven outflows. It is still unknown whether other premotor cell groups are organised this way. Nor are the premotor pathways to 'non-cardiovascular' sympathetic nerves yet well-defined.

C-fos expression in central neurons mediating the arterial baroreceptor reflex.

The immediate early gene c-fos is a transcription regulating factor that is widely employed as a marker of neuronal activation. In this study we have used c-fos expression to identify vasomotor neurons in the brainstem and spinal cord that are activated after interventions that alter blood pressure. These neurons are likely to be those that subserve the arterial baroreceptor reflex and maintain blood pressure within a defined range. With the combination of Fos expression and neuronal tracing, we describe the location and central connections of these neurons. The differential expression of Fos in neurons in separate regions of the brainstem and spinal cord, after either hypotensive or hypertensive stimuli in conscious rats, supports current opinion about baroreflex circuitry. The central processes of baroafferent neurons synapse with second order baroreflex neurons in the nucleus tractus solitarius. From this region baroreceptor information is transmitted to neurons in the caudal ventrolateral medulla and then to neurons in the rostral ventrolateral medulla. The sympathetic preganglionic neurons in the intermediolateral column of the thoracolumbar spinal cord are the final crucial site involved in the arterial baroreflex.