Transient receptor potential vanilloid type 4 is expressed in vasopressinergic neurons within the magnocellular subdivision of the rat paraventricular nucleus of the hypothalamus.

Changes in plasma osmolality can drive changes in the output from brain centres known to control cardiovascular homeostasis, such as the paraventricular nucleus of the hypothalamus (PVN). Within the PVN hypotonicity reduces the firing rate of parvocellular neurons, a neuronal pool known to be involved in modulating sympathetic vasomotor tone. Also present in the PVN is the transient receptor potential vanilloid type 4 (TRPV4) ion channel. Activation of TRPV4 within the PVN mimics the reduction in firing rate of the parvocellular neurons but it is unknown if these neurons express the channel. We used neuronal tracing and immunohistochemistry to investigate which neurons expressed the TRPV4 ion channel protein and its relationship with neurons known to play a role in plasma volume regulation. Spinally projecting preautonomic neurons within the PVN were labelled after spinal cord injection of FluoroGold (FG). This was followed by immunolabelling with anti-TRPV4 antibody in combination with either anti-oxytocin (OXT) or anti-vasopressin (AVP). The TRPV4 ion channel was expressed on 63% of the vasopressinergic magnocellular neurosecretory cells found predominantly within the posterior magnocellular division of the PVN. Oxytocinergic neurons and FG labelled preautonomic neurons were present in the same location, but were distinct from the TRPV4/vasopressin expressing neurons. Vasopressinergic neurons within the supraoptic nucleus (SON) were also found to express TRPV4 and the fibres extending between the SON and PVN. In conclusion within the PVN, TRPV4 is well placed to respond to changes in osmolality by regulating vasopressin secretion, which in turn influences sympathetic output via preautonomic neurons.

A physiological role for nitric oxide in the centrally mediated sympathetic and somatomotor ejaculatory response in anesthetized male Wistar rats.

Neurones in the lumbosacral spinal cord are known to play a significant role in ejaculation. In these same areas neurones containing nitric oxide synthase (NOS) have been described. This raised the question as to whether there is a physiological role for nitrous oxide (NO) in the spinal cord in sexual behavior. We first established immunohistochemical localization of NOS positive neurones in the lumbosacral spinal cord. NOS positive neurones were found in several areas of the lumbosacral cord. Namely the intermediolateral column (IML) at L(1)-L(4) and sacral cord; the dorsal gray commissure above the central canal at L(1)-L(2); the ventral gray area of lamina X below the central canal at L(3)-L(4); the superficial laminae of the dorsal horn at all levels. Secondly, we examined the role of NO in the generation of synchronized bursting activity within the vas deferens nerve and associated penile muscles, typical of sexual responses in the male anesthetized rat. NO modulators were applied directly to the spinal cord at T(13)-L(4) via a catheter placed subdurally (intrathecal) and their effect on the genital responses evoked by systemic administration of p-chloroamphetamine (PCA) or apomorphine (apo) (both 1 mg/kg) was observed. All responses evoked by PCA (n=4) or apo (n=3) were abolished or reduced (n=1) during intrathecal NOS inhibition using N((G)) nitro-L-Arginine methyl ester (l-NAME, 200 mM, 20-microl). NOS inhibition using l-NAME was reversed with simultaneous intrathecal application of the NO substrate l-arginine (100 mM, 20-microl, n=3). The selective neuronal NOS inhibitor 1-(2-trifluoro-methylphenyl) imidazole (100 mM, 20-microl, TRIM) also abolished all responses evoked by PCA (n=3). There was evidence that the responses within the vas deferens nerve (VDN) after PCA or apo were enhanced following NO donation using sodium nitroprusside (SNP, 1 mM, 20-microl). Furthermore, a PCA-like response within the VDN was evoked following intrathecally applied l-glutamic acid (200 mM, 20-microl) in six of 26 animals and also by intrathecal SNP in two of eight animals. In conclusion the results suggest a significant excitatory role for NO in the bursting pattern of synchronized discharge generated in autonomic and somatic outflows from the lumbosacral cord by neurones governing ejaculation.

Inhibition by alpha-tetrahydrodeoxycorticosterone (THDOC) of pre-sympathetic parvocellular neurones in the paraventricular nucleus of rat hypothalamus.

BACKGROUND AND PURPOSE: alpha-tetrahydrodeoxycorticosterone (THDOC) is an endogenous neuroactive steroid which increases in plasma and brain concentration during stress. It has both positive and negative modulatory effects on GABA activated GABAA currents, dependent upon the dose. We investigated the effects of THDOC on spinally-projecting "pre-sympathetic" neurones in the parvocellular subnucleus of the hypothalamic paraventricular nucleus (PVN), to determine whether it activates or inhibits these neurones, and by what mechanism. EXPERIMENTAL APPROACH: Rat spinally-projecting (parvocellular) PVN neurones were identified by retrograde labelling and the action of THDOC investigated with three modes of patch-clamp: cell-attached action current, whole-cell voltage-clamp and cell-attached single-channel recording. KEY RESULTS: In cell-attached patch mode, parvocellular neurones fired action potentials spontaneously with an average frequency of 3.6 +/- 1.1 Hz. Bath application of THDOC reduced this with an EC50 of 67 nM (95% confidence limits: 54 to 84 nM), Hill coefficient 0.8 +/- 0.04, n = 5. In whole-cell patch-clamp mode, pressure ejection of GABA evoked inward currents. These were clearly GABAA currents, since they were inhibited by the GABAA receptor antagonist bicuculline, and reversed near the chloride equilibrium potential. THDOC significantly potentiated GABAA currents (1 microM THDOC: 148 +/- 15% of control, n = 5, p < or = 0.05, ANOVA). Single-channel analysis showed no differences in conductance or corrected mean open times in the presence of 1 microM THDOC. CONCLUSIONS AND IMPLICATIONS: THDOC inhibited parvocellular neuronal activity without showing any evidence of the bidirectional activity demonstrated previously with cultured hypothalamic neurones. Our data are consistent with the hypothesis that THDOC acts by potentiating the post-synaptic activity of endogenously released GABA.

Vagal afferents, sympathetic efferents and the role of the PVN in heart failure.

Sympatho-excitation is a characteristic of cardiovascular disease including heart failure (HF). The paraventricular nucleus of the hypothalamus (PVN) is an important site for central integration of sympathetic outflow. Atrial volume receptors (AVRs) in the wall of the right atrium transduce cardiovascular variables (pressure/volume) into an input that is integrated centrally, in for example, the PVN. Descriptions of the location and structure of the AVRs as well as the molecular mechanism initiating transduction remain scarce, nevertheless preautonomic neurons of the PVN have been consistently identified as making a significant contribution to the sympatho-excitation evident in HF. Furthermore, excitatory and inhibitory interactions within the PVN determine sympathetic tone. A nitric oxide dependent GABAergic inhibition sets the prevailing sympathetic output from the PVN, which in HF becomes dysregulated. Inflammation and oxidative stress have been recognised as possible triggers to the disinhibition. The actions of proinflammatory cytokines and reactive oxygen species in relation to the signalling pathways, which are important in generating sympathetic tone are discussed, as well as the contribution these might make to abnormal control of the sympathetic nervous system in cardiovascular disease.

Altered GABAA α5 subunit expression in the hypothalamic paraventricular nucleus of hypertensive and pregnant rats.

A characteristic of both hypertension and pregnancy is increased sympathetic nerve activity. The level of sympathetic activation is determined, in part, by a tonic GABAergic inhibition arising from the hypothalamic paraventricular nucleus (PVN). In hypertension, decreases in GABAergic inhibition and increases in glutamatergic excitation within the PVN contribute to this sympatho-excitation. In late-term pregnancy however, the sympatho-excitation appears to be mediated by decreases in GABAergic inhibition only. This study examined whether changes in subunit expression for GABAA receptors in the PVN could provide a molecular basis for the sympatho-excitation characteristic of hypertension and pregnancy. Hypertension and pregnancy were accompanied by significant decrease in the GABAA receptor α5 subunit in the PVN. We suggest that decreases in the α5 subunit of the GABAA receptor may be important in mediating the sympatho-excitation observed in both hypertension and pregnancy.

Graphene oxide nanocapsules within silanized hydrogels suitable for electrochemical pseudocapacitors.

Soft biocompatible gels comprised of rolled up graphene oxide nanocapsules within the pores of silanized hydrogels may be used as electrochemical pseudocapacitors with physiological glucose or KOH as a reducing agent, affording a material suitable for devices requiring pulses with characteristic time less than a second.

Evidence that sympathetic preganglionic neurones are arranged in target-specific columns in the thoracic spinal cord of the rat.

It is recognised that selective activation of different target-specific sympathetic preganglionic neurones forms the basis of many autonomic responses. The anatomical basis for this could be the spatial arrangement of these neurones in the spinal cord nuclei. The present study tested this possibility in the rat by determining the location in single animals of three distinct groups of sympathetic preganglionic neurones, one group projecting to the superior cervical ganglion, another to the stellate ganglion and one to the adrenal medulla. Sympathetic preganglionic neurones to each of these targets were simultaneously labeled with fluorescent dyes, either Fluorogold, Fast Blue, or Diamidino Yellow. The numbers and general morphology of the neurones were similar to previous descriptions, and they were distributed in four subnuclei, the nucleus intermediolateralis pars principalis, the nucleus intermediolateralis pars funiculus, the nucleus intercalatus spinalis, and the nucleus intercalatus spinalis pars paraependymalis. It was shown that all three groups of neurones were represented in the more medial sympathetic nuclei, but in the nuclei at the lateral border of the intermediate grey matter each one of the three groups of neurones occupied a discrete location. Adrenal medullary sympathetic preganglionic neurones occupied a lateral aspect, the superior cervical ganglion sympathetic preganglionic neurones a medial aspect, and the stellate ganglion sympathetic preganglionic neurones a space between. Some sympathetic preganglionic neurones were double labeled after dye injections into the superior cervical and stellate ganglion thus indicating that they projected to both ganglia.(ABSTRACT TRUNCATED AT 250 WORDS)

Identification of branching paraventricular neurons of the hypothalamus that project to the rostroventrolateral medulla and spinal cord.

The paraventricular nucleus of the hypothalamus has efferent connections to autonomic nuclei known to ultimately regulate cardiovascular function. Studies have revealed projections to the sympathetic preganglionic neurons of the spinal cord and presympathetic motor neurons of the rostral ventrolateral medulla. This study set out to establish whether the same neurons in the paraventricular nucleus innervate both these regions. In rats the fluorescent neuroanatomical tracers FluoroGold, Fast Blue or Dextran tetramethyl rhodamine were injected into either the rostral ventrolateral medulla or T2 region of the spinal cord. After a suitable survival period (five to seven days) three populations of neurons could be identified in the paraventricular nucleus, double-labelled neurons and single-labelled neurons resulting from the injections into the spinal cord or injections into the rostral ventrolateral medulla. The neurons were of similar size regardless of the dye content. Most neurons were found in the parvocellular subdivision of the mid rostral paraventricular nucleus. The number of labelled neurons decreased in the caudal sections. This study provides an anatomical basis for three means of influence that the paraventricular nucleus can have on sympathetic activity; a hierarchical in series projection via the rostral ventrolateral medulla; a projection running in parallel with this but bypassing the rostroventrolateral medulla; and a branching population innervating neurons in both the rostral ventrolateral medulla and spinal cord. The paraventricular nucleus of the hypothalamus is an important brain area concerned with maintaining cardiovascular homeostasis. This anatomical study has not only provided confirmatory evidence that direct projections arising from the paraventricular hypothalamic nucleus do project to the rostral ventrolateral medulla and spinal cord, regions known to influence cardiovascular regulation. The study has identified a branching projection originating in the paraventricular nucleus of the hypothalamus that projects to both the rostral ventrolateral medulla and the spinal cord. Thus the paraventricular nucleus of the hypothalamus has three pathways in which to influence cardiovascular homeostasis.

Rostroventrolateral medulla neurons preferentially project to target-specified sympathetic preganglionic neurons.

The rostroventrolateral medulla is a key site for the regulation of vasomotor tone. Sympatho-excitatory neurons project from this region to contact sympathetic preganglionic neurons located in the intermediolateral nucleus of the thoracic and lumbat spinal cord. Functional studies show that stimulation of specific sites in the ventral medulla lead to selective activation of different vascular effectors. The present study was designed to determine the anatomical basis for this selectivity in vasomotor control. Anterograde and retrograde tracing methods were utilized to determine if the descending rostral ventrolateral projection is topographically organized such that neurons in particular locations within the nucleus project preferentially and contact a specific group of sympathetic preganglionic neurons. For this purpose spinally-projecting neurons at 15 sites from three separate rostrocaudal locations within the rostroventrolateral medulla in nine rats were anterogradely labelled with biotin dextran amine. The spinal cord was examined for axon terminals having close apposition to two groups of sympathetic preganglionic neurons, those projecting to the superior cervical ganglion and those to the adrenal medulla which were retrogradely labelled with cholera B chain-conjugated horseradish peroxidase. Areas of close apposition between retrogradely-labelled dendrites, cell bodies and anterogradely-labelled axons were found. Axons descending from the more rostral part of the rostroventrolateral medulla produced the highest density of close appositions to sympathetic preganglionic neurons in both target-specific populations. Caudal rostroventrolateral medulla injection sites gave rise to a less dense distribution of axons and terminals around the spinal sympathetic nuclei. This study has demonstrated that spinally-projecting neurons in the rostroventrolateral medulla are both topographically and viscerotopically organized. It is suggested that such an arrangement provides the means for selective and differential control of autonomic effectors and in particular those involved in cardiovascular regulation.

Identification of an efferent projection from the paraventricular nucleus of the hypothalamus terminating close to spinally projecting rostral ventrolateral medullary neurons.

The paraventricular nucleus of the hypothalamus is increasingly being viewed as an important site for cardiovascular integration because of its connections to regions in the brain and spinal cord which are known to be important in cardiovascular control. Like the vasomotor neurons of the rostral ventrolateral medulla, descending axons from paraventricular neurons can be identified that form synapses on sympathetic preganglionic neurons in the thoracic spinal cord. The purpose of this study was to determine whether paraventricular axons project to the rostral ventrolateral medulla and whether they are closely apposed to reticulospinal neurons in this region. Descending paraventricular axons were labelled with biotin dextran amine, while rostral ventrolateral medullary neurons were retrogradely labelled from the spinal cord with wheatgerm agglutinin conjugated to horseradish peroxidase. This revealed, within the rostral ventrolateral medulla, paraventricular axon and terminal varicosities closely apposed to and apparently contiguous with retrogradely labelled spinally projecting neurons. Thus our study at the light microscopical level has shown the potential for the paraventricular nucleus to directly influence rostral ventrolateral reticulospinal neurons. We suggest these connections, if confirmed by electron microscopy, could be one means by which activation of paraventricular neurons elicits alterations in blood pressure.

Measurement of voltage-gated potassium currents in identified spinally-projecting sympathetic neurones of the paraventricular nucleus.

The paraventricular nucleus (PVN) of the hypothalamus modulates cardiovascular function via a sub-population of neurones which project directly to sympathetic centres of the spinal cord. Identification and patch-clamp recording from these neurones is difficult, however, because of the complex organisation and neuronal heterogeneity of the PVN. We report here on methods for the in vitro recording of voltage-gated potassium channel (K(V)) currents from those neurones within the PVN which project to the intermediolateral column of the rat spinal cord, and are believed to directly modulate cardiovascular function. We show K(V) channel currents of spinally projecting neurones to be slowly inactivating (tau >> 100 ms) and weakly sensitive to TEA (K(d)>10 mM). These methods will be useful for the study of K(V) and other ion channel modulation in spinally projecting neurones of the PVN.

Expression of transient receptor potential channels TRPC1 and TRPV4 in venoatrial endocardium of the rat heart.

The atrial volume receptor reflex arc serves to regulate plasma volume. Atrial volume receptors located in the endocardium of the atrial wall undergo mechanical deformation as blood is returned to the atria of the heart. The mechanosensitive channel(s) responsible for regulating plasma volume remain to be determined. Here we report that the TRP channel family members TRPC1 and TRPV4 were expressed in sensory nerve endings in the atrial endocardium. Furthermore, TRPC1 and TRPV4 were coincident with the nerve ending vesicle marker synaptophysin. Calcitonin gene-related peptide was exclusively confined to the myo- and epicardium of the atria. The small conductance Ca(2+)-activated K(+) channels (SK2 and SK4) were also present, however there was no relationship between SK and TRP channels. SK2 channels were expressed in nerves in the epicardium, while SK4 channels were in some regions of the endocardium but appeared to be present in epithelial cells rather than sensory endings. In conclusion, we have provided the first evidence for TRPC1 and TRPV4 channels as potential contributors to mechanosensation in the atrial volume receptors.

The projection and synaptic organisation of NTS afferent connections with presympathetic neurons, GABA and nNOS neurons in the paraventricular nucleus of the hypothalamus.

Elevated sympathetic nerve activity, strongly associated with cardiovascular disease, is partly generated from the presympathetic neurons of the paraventricular nucleus of the hypothalamus (PVN). The PVN-presympathetic neurons regulating cardiac and vasomotor sympathetic activity receive information about cardiovascular status from receptors in the heart and circulation. These receptors signal changes via afferent neurons terminating in the nucleus tractus solitarius (NTS), some of which may result in excitation or inhibition of PVN-presympathetic neurons. Understanding the anatomy and neurochemistry of NTS afferent connections within the PVN could provide important clues to the impairment in homeostasis cardiovascular control associated with disease. Transynaptic labelling has shown the presence of neuronal nitric oxide synthase (nNOS)-containing neurons and GABA interneurons that terminate on presympathetic PVN neurons any of which may be the target for NTS afferents. So far NTS connections to these diverse neuronal pools have not been demonstrated and were investigated in this study. Anterograde (biotin dextran amine - BDA) labelling of the ascending projection from the NTS and retrograde (fluorogold - FG or cholera toxin B subunit - CTB) labelling of PVN presympathetic neurons combined with immunohistochemistry for GABA and nNOS was used to identify the terminal neuronal targets of the ascending projection from the NTS. It was shown that NTS afferent terminals are apposed to either PVN-GABA interneurons or to nitric oxide producing neurons or even directly to presympathetic neurons. Furthermore, there was evidence that some NTS axons were positive for vesicular glutamate transporter 2 (vGLUT2). The data provide an anatomical basis for the different functions of cardiovascular receptors that mediate their actions via the NTS-PVN pathways.

Neurochemistry of the paraventricular nucleus of the hypothalamus: implications for cardiovascular regulation.

The paraventricular nucleus of the hypothalamus (PVN) is an important site for autonomic and endocrine homeostasis. The PVN integrates specific afferent stimuli to produce an appropriate differential sympathetic output. The neural circuitry and some of the neurochemical substrates within this circuitry are discussed. The PVN has at least three neural circuits to alter sympathetic activity and cardiovascular regulation. These pathways innervate the vasculature and organs such as the heart, kidney and adrenal medulla. The basal level of sympathetic tone at any given time is dependent upon excitatory and inhibitory inputs. Under normal circumstances the sympathetic nervous system is tonically inhibited. This inhibition is dependent upon GABA and nitric oxide such that nitric oxide potentiates local GABAergic synaptic inputs onto the neurones in the PVN. Excitatory neurotransmitters such as glutamate and angiotensin II modify the tonic inhibitory activity. The neurotransmitters oxytocin, vasopressin and dopamine have been shown to affect cardiovascular function. These neurotransmitters are found in neurones of the PVN and within the spinal cord. Oxytocin and vasopressin terminal fibres are closely associated with sympathetic preganglionic neurones (SPNs). Sympathetic preganglionic neurones have been shown to express receptors for oxytocin, vasopressin and dopamine. Oxytocin causes cardioacceleratory and pressor effects that are greatest in the upper thoracic cord while vasopressin cause these effects but more significant in the lower thoracic cord. Dopaminergic effects on the cardiovascular system include inhibitory or excitatory actions attributed to a direct PVN influence or via interneuronal connections to sympathetic preganglionic neurones.

An immunohistochemical investigation of the relationship between neuronal nitric oxide synthase, GABA and presympathetic paraventricular neurons in the hypothalamus.

Functional studies suggest that nitric oxide (NO) modulates sympathetic outflow by enhancing synaptic GABAergic function. Furthermore, the paraventricular nucleus of the hypothalamus (PVN), an important site for autonomic and endocrine homeostasis constitutes an important center mediating NO actions on sympathetic outflow. However, the exact anatomical organization of GABA and NO releasing neurons with the PVN neurons that regulate autonomic activity is poorly understood. The present study addressed this by identifying PVN-presympathetic neurons in the rat with the retrograde tracer Fluorogold injected into T2 segment of the spinal cord or herpes simplex virus injected into the adrenal medulla (AM). GABAergic or nitric oxide cell bodies were identified by antibodies directed towards GABA or glutamate decarboxylase (GAD67) enzyme or neuronal nitric oxide synthase. This revealed a population of GABAergic neurons to be synaptically associated with a chain of pre-sympathetic neurons targeting the AM. Furthermore, this GABAergic population is not a cellular source of NO. Within the PVN, the majority of cellular nitric oxide was localized to non-spinally projecting neurons while for the PVN-spinally projecting neuronal pool only a minority of neuron were immunopositive for neuronal nitric oxide synthase. In summary, nitrergic and GABAergic neurons are associated with a hierarchical chain of neurons that regulate autonomic outflow. This anatomical arrangement supports the known function role of a NO-GABA modulation of sympathetic outflow.

Arrangement of dendrites and morphological characteristics of sympathetic preganglionic neurones projecting to the superior cervical ganglion and adrenal medulla in adult cat.

Sympathetic preganglionic neurones (SPN) projecting to the superior cervical ganglion (SCG) and adrenal medulla (AM) in the adult cat were retrogradely labelled with cholera B horseradish peroxidase (CBHRP). Labelled neurones were found in 4 sub-nuclei: the nucleus intermediolateralis thoracolumbalis pars principalis (ILp), the nucleus intermediolateralis pars funicularis (ILf), the nucleus intercalatus spinalis (IC) and the nucleus pars paraependymatis (ICpe). The majority of SPN were found in the ILp (75%). Each group of target specified SPN had a different segmental distribution. SCG-SPN between cervical 8 (C8) and thoracic 6 (T6) and AM-SPN between thoracic 3 (T3) and lumbar 2 (L2). Fusiform and round bodied neurones were the most common shapes found, a third longitudinal type was occasionally found. SCG and AM-SPN exhibited a dense rostrocaudal dendritic projection extending along the length of the ILp. There was also a lateral projection into the ILf and a medial one projecting towards the central canal. This dendritic arrangement gave the ILp the appearance of being an 'open nucleus'. The dendrites branched at their distal ends and all along their lengths swellings could be seen. It was concluded that contrary to previous descriptions the arrangement of SPN in the adult cat is not too dissimilar to that in the adult rat.

A comparison between the adult rat and neonate rat of the architecture of sympathetic preganglionic neurones projecting to the superior cervical ganglion, stellate ganglion and adrenal medulla.

Sympathetic preganglionic neurones (SPN) projecting to the superior cervical ganglion (SCG) and adrenal medulla (AM) in the neonate (< 14 days) and SCG, stellate ganglion (SG) and AM in the adult rat (> 3 months) were retrogradely labelled with cholera B horseradish peroxidase (CBHRP). Labelled neurones were found in 4 four distinct nuclei: the nucleus intermediolateralis thoracolumbalis pars principalis (ILp), a nucleus equivalent to the intemediolateral cell column (IML); the nucleus intermediolateralis thoracolumbalis pars funicularis (ILf); the nucleus intercalatus spinalis (IC) and the nucleus intercalatus pars paraependymatis (ICpe) or central autonomic area (CA). These were represented to a similar extent in both neonate and adult. Neonate and adult SCG, SG and AM-SPN had a similar segmental distribution cervical 8 (C8) to thoracic 5 (T5) for SCG-SPN and thoracic 3 (T3) to thoracic (T13) for AM-SPN whereas adult SG-SPN were distributed over segments C8 to T9. Most labelled neurones (70%) were located in the ILp with one segment containing the highest proportion of SPN. Three morphologically distinct neurones were evident. Fusiform and roundbodied were the most common. Fusiform somata of the ILp were orientated both mediolaterally and rostrocaudally in the neonate but only rostrocaudally in the adult. Dendrites of the SPN in the adult and neonate extended in a dense rostrocaudal band along the ILp, more diffusely into the white matter of the Ilf and in bundles medially towards the central canal (CC). The neonate showed some significant differences. In the ILp, the cell bodies were less tightly packed into a narrow band and into clusters and the dendrites were more diffuse. It was concluded that at 12 days postnatally the organisation of the sympathetic nuclei had still nor reached the adult form. However, there is no extensive realignment of dendrites in the adult so the ILp remains an 'open' nucleus like the neonate.

Control of sympathetic outflows by the hypothalamic paraventricular nucleus.

1. The functional role of the paraventricular nucleus (PVN) has been examined by studying its connections with cardiovascular neurons in the medulla and spinal cord and its influence on activity in several sympathetic nerves. 2. Chemical stimulation of neurons within the PVN can elicit pressor responses and can excite reticulo-spinal vasomotor neurons in the rostral ventrolateral medulla (RVLM). 3. The PVN-RVLM excitation is blocked by kynurenic acid applied iontophoretically in the vicinity of RVLM-spinal neurons, suggesting this is a glutamate-dependent pathway. 4. Electrical stimulation of PVN neurons evoked action potentials in RVLM neurons after 27 ms with a small variability. 5. Anterograde and retrograde labelling of PVN and RVLM neurons revealed PVN terminals closely associated with RVLM-spinal neurons and showed that the PVN is connected to the spinal cord via three pathways. 6. Chemical activation of PVN neurons can produce a pattern of activation of cardiovascular neurons similar to that occurring in defence against plasma volume expansion. 7. It is concluded that the PVN connections with the RVLM and spinal cord are important to a role in defending against life-threatening disturbances.

Right atrial stretch induces renal nerve inhibition and c-fos expression in parvocellular neurones of the paraventricular nucleus in rats.

The paraventricular nucleus of the hypothalamus plays a pivotal role in the regulation of plasma volume. Part of the response to an increase in volume load is an inhibition of renal sympathetic nerve activity. The present experiments were designed to determine which subnuclei of the paraventricular nucleus are involved in this sympatho-inhibitory response. Experiments were performed on anaesthetised rats. Activated neurones were recognised by the expression of the early gene c-fos, identified by immunohistochemical labelling of its protein product Fos. Plasma volume loading with 4 % Ficoll 70, using an infusion-withdrawal procedure (2 ml over 1 min) repeated 15 times over 1 h revealed a total of 775 +/- 101 (n = 6) Fos-positive neurones scattered throughout both the magnocellular and parvocellular subnuclei. In comparison, sustained hypertension resulted in 452 +/- 56 (n = 3) Fos-positive neurones similarly distributed, whereas a normotensive control group (n = 3) displayed 115 +/- 18 Fos-positive neurones. Because of this lack of a specific effect we used a more selective stimulation of right atrial receptors via a balloon placed at the junction of the superior vena cava and the right atrium so it did not impede venous return. Inflation of the balloon inhibited renal sympathetic nerve activity (36 +/- 5 %, n = 7) and repetitive inflation over 1 h resulted in c-fos activation of a small number of neurones (54 +/- 14) located only in the parvocellular subnuclei. Whether these are inhibitory interneurones acting within the paraventricular nucleus, or spinally projecting neurones which inhibit or excite renal sympathetic activity by an action in the spinal cord remains to be determined.