Effects of intracerebroventricular administration of neuropeptide W30 on neurons in the hypothalamic paraventricular nucleus in the conscious rat.

We demonstrated that intracerebroventricular (i.c.v.) administration of NPW30 increases the arterial blood pressure (ABP), heart rate (HR), and plasma catecholamine concentrations in conscious rats. NPW has been reported to be an important stress mediator in the central nervous system that modulates the hypothalamus-pituitary-adrenal (HPA) axis and sympathetic outflow. To examine the effects of NPW30 on the neural activity of the hypothalamic paraventricular nucleus (PVN), which is an integrative center of the autonomic and endocrine functions relevant to stress responses, we simultaneously recorded the single-unit activity in the PVN, ABP, and HR in conscious freely moving rats. Of the non-phasic (irregular) PVN neurons (n=35) examined, NPW30 (i.c.v. 3 nmol) elicited excitation in 22 neurons, inhibition in 7 neurons, and no response in 6 neurons, accompanied with increases in ABP and HR, whereas low-dose NPW30 (i.c.v. 0.3 nmol) did not affect the unit activity, ABP, or HR. Neurons that were affected by NPW30 were then further examined for their responses to perturbation in ABP and systemic administration of cholecystokinin-8 (CCK). The majority of neurons also showed responses to CCK, phenylephrine (PE), or nitroprusside (SNP). Our data suggest that central NPW30 modulates PVN neuronal activities, which might be involved in the regulation of cardiovascular function and energy balance through the autonomic nervous system, particularly, under stress-related conditions.

[Central action of orexins on sympathetic outflow and cardiovascular function with a focus on the paraventricular nucleus of the hypothalamus].

Orexins were initially reported as regulators of food intake. More recent reports suggest that they might play roles in the multiple functions of neuronal systems, causing medical conditions such as narcolepsy, a sleep disorder. Orexins and their receptors (OX1R and OX2R) are distributed in the neural tissue and brain regions involved in the autonomic and neuroendocrine control. Within the hypothalamus, orexin fibers and orexin receptors, especially OX2R, are found extensively in the paraventricular nucleus (PVN) of the hypothalamus. The PVN is an integrative center of the autonomic nervous system and the neuroendocrine system. Thus, orexins may play a role in the regulation of cardiovascular and autonomic nervous systems. This article provides a summary of our studies, in which we used direct recording of renal sympathetic nerve and PVN neuronal activities in conscious freely-moving rats and the in vitro whole cell patch-clamp technique to examine the direct effect of orexins on PVN neurons using a hypothalamic slice. Functional studies demonstrated that intracerebroventricularly (i.c.v.) administered orexins evoke increases in blood pressure, heart rate, and sympathetic nerve activity and depolarize both the magno- and parvo-cellular neurons through the activation of non-selective cation channels. The present studies suggest that PVN plays a role as one of the efferent pathways of orexin-induced activation of the sympathetic outflow.

Cardiovascular actions of central neuropeptide W in conscious rats.

Neuropeptide W (NPW) is a novel hypothalamic peptide that activates the orphan G protein-coupled receptors, GPR7 and GPR8. Two endogenous molecular forms of NPW that consist of 23- and 30-amino acid residues were identified. Intracerebroventricular (i.c.v.) administration of NPW is known to suppress spontaneous-feeding at dark-phase and fasting-induced food intake and to decrease body weight and plasma growth hormone and to increase prolactin and corticosterone; however, little is known about its effect on other physiological functions. We examined the effects of i.c.v. administration of NPW30 (0.3 and 3 nmol) on the mean arterial pressure (MAP), heart rate (HR), and plasma norepinephrine and epinephrine in conscious rats. NPW30 (3 nmol) provoked increases in MAP (85.12+/-3.16 to 106.26+/-2.66 mm Hg) and HR (305.75+/-13.76 to 428.45+/-26.82 beats/min) and plasma norepinephrine (138.1+/-18.1 to 297.2+/-25.9 pg/ml) and epinephrine (194.6+/-21.4 to 274.6+/-22.7 pg/ml). Intravenously administered NPW30 (3 nmol) had no significant effects on MAP and HR. These results indicate that central NPW30 increases sympathetic nervous outflow and affects cardiovascular function.

Enhanced cardiovascular alteration and Fos expression induced by central salt loading in a conscious rat transgenic for the metallothionein-vasopressin fusion gene.

The present study is an investigation of the responses of the cardiovascular system and Fos expression to intracerebroventricular (i.c.v.) administration of hypertonic saline (HS) in conscious arginine vasopressin (AVP)-overexpressing transgenic (Tg) and control rats. Central HS (0.3, 0.67, or 1.0M NaCl, 1 microl/min for 20 min) significantly increased the mean arterial blood pressure (MABP) and Fos-like immunoreactivity (FLI) in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus, the area postrema (AP), the median preoptic nucleus (MnPO), and the organum vasculosum laminae terminalis (OVLT) in both Tg and control rats. The changes in MABP and FLI were significantly larger in Tg rats than in control rats. i.c.v. pretreatment with the AVP V1 receptor antagonist, OPC-21268, blocked the increase in MABP and significantly decreased the Fos expression in the PVN (posterior magnocellular (pm) component) induced by 0.3 M HS in the Tg rats. The present study demonstrates an increased responsiveness to i.c.v. administration of HS in AVP Tg rats, suggesting the relationship between the vasopressinergic drive and central cardiovascular response via, at least in part, the V1 receptor in the PVN magnocellular neurons.

Central stresscopin modulates cardiovascular function through the adrenal medulla in conscious rats.

Stresscopin (SCP or urocortin III), a member of the corticotropin-releasing factor (CRF) neuropeptide family, is a high-affinity ligand for the type 2 CRF receptor (CRF(2)). When administered peripherally, SCP suppresses food intake, delays gastric emptying and decreases heat-induced edema. Central administration of CRF produces marked hypertension and increased plasma catecholamine. However, the effects of SCP on the cardiovascular system are unknown. Thus, the present study compared the effects of intracerebroventricular (i.c.v.) administration of CRF and SCP on cardiovascular function. Central administration of SCP (0.05 or 0.5 nmol) elicited transient increases in mean arterial blood pressure (MABP) and heart rate (HR), and the higher dose of SCP (0.5 nmol) resulted in increased plasma epinephrine. In contrast, central administration of CRF provoked long-lasting increases in MABP, HR and plasma catecholamine levels (norepinephrine and epinephrine). Intravenously administered CRF and SCP (0.5 nmol) did not elicit significant changes in MABP and HR. Therefore, these data suggest that centrally administered SCP modulates cardiovascular function, likely through the sympatho-adrenal-medullary (SAM) system.

Effect of hypertonic saline on rat hypothalamic paraventricular nucleus magnocellular neurons in vitro.

The effect of hypertonic saline on rat hypothalamic paraventricular nucleus (PVN) magnocellular neurons was examined using a whole-cell patch-clamp technique. Under a current-clamp, 58/68 of magnocellular neurons were depolarized by hypertonic stimulation. Under a voltage-clamp, hypertonic saline produced an inward current via increased non-selective cationic conductance and shifting of the reversal potential to more positive values. Furthermore, hypertonic saline even without a change in osmolality increased spontaneous excitatory postsynaptic currents (sEPSCs). A bath application of CNQX almost completely blocked EPSCs. Extracellular application of gadolinium blocked the hypertonic saline- and mannitol-induced response. These results suggest that PVN magnocellular neurons are responsive to osmolality and Na+ concentrations. Hypertonic saline excited PVN magnocellular neurons via osmo-reception, Na+ -detection, and excitatory glutamatergic synaptic input.