Cardiac sympatho-excitatory action of PVN-spinal oxytocin neurones (original) (raw)

Oxytocin promotes functional coupling between paraventricular nucleus and both sympathetic and parasympathetic cardioregulatory nuclei

The neuropeptide oxytocin (OXT) facilitates prosocial behavior and selective sociality. In the context of stress, OXT also can down-regulate hypothalamic–pituitary–adrenal (HPA) axis activity, leading to consideration of OXT as a potential treatment for many socioaffective disorders. However, the mechanisms through which administration of exogenous OXT modulates social behavior in stressful environmental contexts are not fully understood. Here, we investigate the hypothesis that autonomic pathways are components of the mechanisms through which OXT aids the recruitment of social resources in stressful contexts that may elicit mobilized behav-ioral responses. Female prairie voles (Microtus ochrogaster) underwent a stressor (walking in shallow water) following pretreatment with intraperitoneal OXT (0.25 mg/kg) or OXT antagonist (OXT-A, 20 mg/kg), and were allowed to recover with or without their sibling cagemate. Administration of OXT resulted in elevated OXT concentrations in plasma, but did not dampen the HPA axis response to a stressor. However, OXT, but not OXT-A, pre-treatment prevented the functional coupling, usually seen in the absence of OXT, between paraventricular nucleus (PVN) activity as measured by c-Fos immunoreactivity and HPA output (i.e. corticosterone release). Furthermore , OXT pretreatment resulted in functional coupling between PVN activity and brain regions regulating both sympathetic (i.e. rostral ventrolateral medulla) and parasympathetic (i.e. dorsal vagal complex and nucleus ambiguous) branches of the autonomic nervous system. These findings suggest that OXT increases central neural control of autonomic activity, rather than strictly dampening HPA axis activity, and provides a potential mechanism through which OXT may facilitate adaptive and context-dependent behavioral and physiological responses to stressors.

Neuropeptides, amines and amino acids as mediators of the sympathetic effects of paraventricular nucleus activation in the rat

Experimental Physiology, 2002

The aim of the present study was to determine the influence on renal sympathetic nerve activity of the different chemically coded neuronal phenotypes that project from the paraventricular nucleus (PVN) to the spinal cord. Experiments were carried out on male Wistar rats anaesthetised with chloralose and urethane. Changes in renal sympathetic nerve activity were measured following activation of neurones in the PVN with D,L-homocysteic acid (100 nl, 200 mM), before and following intrathecal application of glutamate, vasopressin, oxytocin, dopamine and their receptor antagonists. Excitatory and inhibitory effects on renal sympathetic nerve activity were elicited by PVN stimulation. PVN excitatory effects were mimicked by intrathecal administration of glutamate and vasopressin and selectively antagonised by intrathecal administration of kynurenic acid and a V 1a receptor antagonist, respectively. A low dose of dopamine increased renal sympathetic activity and this was selectively antagonised by haloperidol; however, the latter was without effect on PVN excitatory responses. A high dose of dopamine decreased renal sympathetic nerve activity and this was selectively blocked by a D1 dopamine receptor antagonist (SCH 23390), which also antagonised a minority of inhibitory responses obtained from the caudal extension of the PVN. Oxytocin also had two actions: in 5 rats it inhibited and in 10 rats it increased renal sympathetic nerve activity, both actions being blocked selectively by oxytocin receptor antagonists. Neither of the PVN effects on renal sympathetic nerve activity appeared to be dependent on oxytocin pathways. Tests with intrathecal administration of bicuculline showed that PVN inhibition of renal sympathetic nerve activity was not dependent on spinal GABA A receptor activation. The results show that PVN-induced excitation of sympathetic activity to the kidney is mainly mediated by glutamate or vasopressin neurones whereas dopamine via D1 receptors may mediate some of the PVN inhibitory effects.

Baroreflex control of heart rate by oxytocin in the solitary-vagal complex

American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, 2002

Previous work demonstrated that oxytocinergic projections to the solitary vagal complex are involved in the restraint of exercise-induced tachycardia (2). In the present study, we tested the idea that oxytocin (OT) terminals in the solitary vagal complex [nucleus of the solitary tract (NTS)/dorsal motor nucleus of the vagus (DMV)] are involved in baroreceptor reflex control of heart rate (HR). Studies were conducted in male rats instrumented for chronic cardiovascular monitoring with a cannula in the NTS/DMV for brain injections. Basal mean arterial pressure and HR and reflex HR responses during loading and unloading of the baroreceptors (phenylephrine/sodium nitroprusside intravenously) were recorded after administration of a selective OT antagonist (OTant) or OT into the NTS/DMV. The NTS/DMV was selected for study because this region contains such a specific and dense concentration of OT-immunoreactive terminals. Vehicle injections served as a control. OT and OTant changed baroref...

Role of paraventricular nucleus in the cardiogenic sympathetic reflex in rats

American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2004

Myocardial ischemia stimulates cardiac spinal afferents to initiate a sympathoexcitatory reflex. However, the pathways responsible for generation of increased sympathetic outflow in this reflex are not fully known. In this study, we determined the role of the paraventricular nucleus (PVN) in the cardiogenic sympathetic reflex. Renal sympathetic nerve activity (RSNA) and blood pressure were recorded in anesthetized rats during epicardial application of 10 μg/ml bradykinin. Bilateral microinjection of muscimol (0.5 nmol), a GABAA receptor agonist, was performed to inhibit the PVN. In 10 vehicle-injected rats, epicardial bradykinin significantly increased RSNA 178.4 ± 48.5% from baseline, and mean arterial pressure from 76.9 ± 2.0 to 102.3 ± 3.3 mmHg. Microinjection of muscimol into the PVN significantly reduced the basal blood pressure and RSNA ( n = 12). After muscimol injection, the bradykinin-induced increases in RSNA (111.6 ± 35.9% from baseline) and mean arterial pressure (61.2 ±...

Oxytocin acts at V1 receptors to excite sympathetic preganglionic neurones in neonate rat spinal cord in vitro

Brain Research, 1994

Intracellular recordings were made from sympathetic preganglionic neurones (SPNs) in transverse slices of thoraco-lumbar spinal cord of young rats (12-20 days old). A small group of SPNs generally having higher membrane potentials (-70 mV) compared to a remaining group (-66 mV) showed spontaneous oscillations of their membrane potential. Oxytocin superfused in concentrations of 0.1-30 /zM had four effects on SPNs, inducing slow depolarisation, EPSPs, IPSPs and brief rhythmic oscillations. The slow depolarisation was unaffected by TTX whereas this abolished the other changes. The oxytocin-induced depolarisation was associated with a slow inward current and was not reversed at membrane potentials negative to E K, it increased at more positive potentials and was still present in low Ca 2+ and high Mg 2+ solutions. These features of the oxytocin induced current are similar to those of the TFX resistant voltage dependent Na + current described in brainstem autonomic neurones. Vasopressin superfused at concentrations of 0.1 #M to 30/zM had similar effects on SPNs to those of oxytocin. A comparison of the effects of oxytocin and vasopressin on the same neurones revealed that oxytocin was almost 10 times less potent than vasopressin. The effects of oxytocin were not mimicked by a selective oxytocin agonist but were mimicked by a selective vasopressin Via agonist and blocked by a selective Via antagonist. Therefore it is concluded that the effects of oxytocin on SPNs are mediated by the vasopressin Via receptor. It is suggested that oxytocin and vasopressin terminals in the lateral horn are part of a descending system controlling oscillating networks of SPNs in the spinal cord.

Oxytocin and electrical stimulation of the paraventricular hypothalamic nucleus produce antinociceptive effects that are reversed by an oxytocin antagonist

PAIN, 2006

In recent years, oxytocin has been implicated in a wide diversity of functions. The role of oxytocin in analgesia and pain modulation represents an important new function of an endogenous system controlling sensorial information. The paraventricular (PV) nucleus of the hypothalamus is one of the most important sources of oxytocin, and it has a very well-defined projection to the spinal cord. The location of this PV spinal cord projection correlates well with oxytocin binding sites at the dorsal horn of the spinal cord. In this work, we used rats with a chronic (46 days) sciatic loose ligature, an electrical stimulating electrode, and an intrathecal cannula, which reached the L4-L5 levels of the spinal cord. We compared the oxytocin effects with electrical stimulation of the PV and observed a significant reduction of the withdrawal responses to mechanical and cold stimulation applied to the ipsilateral and contralateral hind paws. An oxytocin antagonist administered intrathecally blocked the PV effects. Naloxone was also intrathecally injected 2 min before the PV stimulation, and we also observed a significant reduction of the withdrawal responses; however, this reduction was less pronounced. Our results support the hypothesis that oxytocin is part of the descending inhibitory control mechanisms having an important antinociceptive action. We cannot exclude a minor opiate participation in the OT action. Ó

The Paraventricular Oxytocin Neurons are Involved in Neural Modulation of Breathing

2001

In this study, we determined the projections of oxytocin-containing neurons of the paraventricular nucleus (PVN) to phrenic nuclei and to the rostral ventrolateral medullary (RVLM) region known to be involved in respiratory rhythm generation. Studies were also designed to determine oxytocin receptor expression within the RVLM, and the physiological effects of their activation on respiratory drive and arterial blood pressure. Oxytocin immunohistochemistry combined with cholera toxin B (CT-b), a retrograde tracer, showed that a subpopulation of oxytocin-containing parvocellular neurons in the dorsal and medial ventral regions of the PVN project to phrenic nuclei. Similarly, a subpopulation of psuedorabies virus (PRV) labeled neurons in the PVN coexpressed oxytocin after injection of PRV, a transynaptic retrograde marker, into the costal region of the diaphragm. A subpopulation of oxytocin expressing neurons was also found to project to the RVLM. Activation of this site by microinjection of oxytocin into the RVLM (0.2 nmol/200nl) significantly increased diaphragm electromyographic activity (D EMG ) and frequency discharge (P<0.05). In addition, oxytocin increased blood pressure and heart rate (P<0.05). These data indicate that oxytocin participates in the regulation of respiratory and cardiovascular activity, partly via projections to the RVLM and phrenic nuclei.

A role for the paraventricular nucleus of the hypothalamus in the autonomic control of heart and kidney

Experimental Physiology, 2005

It is now well accepted that the sympathetic nervous system responds to specific afferent stimuli in a unique non-uniform fashion. The means by which the brain transforms the signals from a single type of receptor into an appropriate differential sympathetic output is discussed in this brief review. The detection of and response to venous filling are used for illustration. An expansion of blood volume has been shown in a number of species to increase heart rate reflexly via sympathetic nerves and this effect is primarily an action of volume receptors at the venous-atrial junctions of the heart. Stimulation of these volume receptors also leads to an inhibition of renal sympathetic nerve activity. Thus the reflex response to an increase in plasma volume consists of a distinctive unique pattern of sympathetic activity to maintain fluid balance.

Responses of electrophysiologically identified rat paraventricular neurons to cholecystokinin and other stimuli

Neuroscience, 1995

Extracellular recordings were carried out in the paraventricular nucleus of halothane-anesthetized male rats. Responses of neurons identified by antidromic criteria with projections to the nucleus tractus solitarius or to the ventral lateral medulla were compared to those of neurohypophysial neurons following alterations in blood pressure and osmolarity, hemorrhage and after intravenous injection of cholecystokinin. Neurohypophysial neurons displayed the well-described responses to blood pressure for putative vasopressin neurons and increases in excitability after cholecystokinin for putative oxytocin neurons. Twenty per cent of the ventral lateral medulla-projecting neurons were responsive to cardiovascular perturbations, with these displaying reduced activity after either decreases or increases in blood pressure. None of nine neurons projecting to the ventral lateral medulla responded to i.v. cholecystokinin. Two of 20 nucleus tractus solitarius-projecting neurons showed reduced activity after cholecystokinin and none increased their firing rate. Nitroprusside-induced hypotension was associated with reduced activity in 10% of this population. Three neurons displayed axon projections to both pituitary and medulla; two of these which projected to the nucleus tractus solitarius were activated by cholecystokinin. We conclude that some of the paraventricular nucleus neurons projecting to the medulla respond to recognized cardiovascular stimuli for neurohypophysial neurons, but neurons in these populations are generally unresponsive to cholecystokinin. The former group of neurons may act to coordinate autonomic and endocrine responses to cardiovascular perturbation; however, there may be other stimuli, such as cholecystokinin, which act only on one of the populations of paraventricular nucleus neurons. Furthermore, many neurons in the descending pathways may respond to stimuli not presently associated with activation of magnocellular neurons.

Effects of Lysine-Vasopressin and Oxytocin on Central Cardiovascular Control

British Journal of Pharmacology, 1982

The cardiovascular effects of intravenous and intracisternal administration of neurohypophysial peptides were compared in dogs anaesthetized with chloralose. 2 Intravenous lysine-vasopressin (0.1 to 100 mu/kg) induced a dose-dependent increase in blood pressure and a decrease in heart rate. In contrast, intracisternal lysine-vasopressin (0.01 to 10 mu/kg) induced a dose-related decrease in blood pressure and did not change heart rate. 3 Intracisternal oxytocin (1 and 10 mu/kg) increased blood pressure and did not change heart rate, whereas the same doses injected intravenously were inactive. 4 Pretreatment with guanethidine (15 mg/kg i.v. 24 h beforehand) abolished the hypotensive responses to intracisternal vasopressin but not the pressor action of intravenous vasopressin. 5 The pressor responses to central injections of oxytocin were not modified by guanethidine. 6 Hypotension elicited by intracisternal vasopressin was probably due to a decrease in sympathetic tone whereas the hypertension induced by intracisternal oxytocin was independent of variations in sympathetic tone.