Regulatory mechanism of the ventromedial hypothalamus in enhancing glucose uptake in skeletal muscles

To evaluate roles of the sympathetic nervous system in enhancing glucose uptake in skeletal muscles in response to electrical stimulation of the ventromedial hypothalamic nucleus (VMH), the effects of guanethidine treatment and adrenal demedullation on the response were examined in rats anesthetized and injected with muscle relaxant, pancuronium bromide. Pretreatment with guanethidine effectively suppressed the increase in the rate constant of glucose uptake, measured by the 2-deoxy-d-[³H]glucose method, in skeletal muscles upon VMH stimulation. However, bilateral adrenodemedullation had no significant effect. These results suggest that the VMH is intimately concerned in the regulation of glucose uptake in skeletal muscles through intermediation of the sympathetic nerves.     

Intra-ventromedial hypothalamic injection of glutamate stimulates brown adipose tissue thermogenesis in the rat

The ventromedial hypothalamic nucleus (VMH) has been recognized for its role in the control of thermogenesis in brown adipose tissue (BAT) in the rat. However, the neural elements within the VMH that might be involved have not been clearly identified. In the present study, intra-VMH microinjections of the excitatory amino acid glutamate (100 mM to 1 M, in 0.25 μl), which excites cell bodies and dendrites but not axons and nerve terminals, dose-dependently increased interscapular BAT (IBAT) temperature in urethane-anaesthetized rats. This effect of glutamate was blocked by prior treatment with the sympathetic ganglionic blocker, chlorisondamine chloride (2.5 mg/kg, i.p.) or the β-adrenergic receptor antagonist, propranolol (2.5 mg/kg, i.p.), implicating the involvement of sympathetic norepinephrine. These results are consistent with the view that cells in the VMH are implicated in the transmission of thermogenic signals to BAT.     

Hypothalamic stimulation induces vagally mediated hypocalcemia in the rat

A hypothalamo-vagal mechanism of immobilization (IMB) stress-induced hypocalcemia was investigated in rats. Bilateral lesions in the Ventromedial nucleus of the hypothalamus (VMH), but not those of the lateral hypothalamic area (LHA) or the paraventricular nucleus (PVN), eliminated the calcium-lowering effect of IMB. None of these lesions, however, affected the basal levels of the blood calcium. An electrical stimulation of the VMH induced a significant decrease in the blood calcium level (0.07 mM fall) 60 min after stimulation. The hypocalcemic response was eliminated by a vagotomy of the gastric branches but not by that of the thyroid/parathyroid branches. These results suggest that the VMH mediates IMB-induced hypocalcemia through its influence on the gastric vagus.     

Hypothalamic control of gastric acid secretion

Study of hypothalamic control of gastric acid scretion (GAS) has revealed GAS-related neurons, their location in the lateral hypothalamic area (LHA), their characteristics, and implications of their relations to feeding and other functions. Some LHA glucose-sensitive neurons are referred to as gastric type because of their effects on gastric oxyntic cells via specific gastric related neurons of the medulla oblongata and the vagus. The 2-deoxy-D-glucose (2-DG), or insulin induced GAS was completely abolished by bilateral subdiaphragmatic vagotomy, or micro-lesions in specific sites of the LHA. These gastric type glucose-sensitive neurons were thus believed to contribute to control of GAS. The paraventricular nucleus (PVN) was also found to affect GAS. GAS-related PVN neurons were observed in the rostral PVN. Electrophoretic application of various chemicals, especially glucose, also affected neurons in the rostral PVN. Electrophoretically applied norepinephrine (NE) increased PVN single neuron activity and suppressed GAS. Results suggest that the rostral PVN may be another site to modulate LHA control of GAS, and NE may be a transmitter or modulator.     

Glutamate injection into the suprachiasmatic nucleus stimulates brown fat thermogenesis in the rat

Injection of glutamate (100 mM to 1 M, in 0.25 μl saline) into the hypothalamic suprachiasmatic nucleus (SCN) dose-dependently increased interscapular brown adipose tissue (IBAT) and core temperatures in the urethane-anaesthetized rat. This effect was more pronounced in rats tested during the light-off period than in animals tested during the light-on period. Prior injection of the local anaesthetic, procaine (5% in 0.5 μl saline), into the ipsilateral ventromedial hypothalamic nucleus (VMH) attenuated the increases in IBAT and core temperatures induced by intra-SCN glutamate. The VMH has previously been implicated in the central regulation of BAT thermogenesis; the present results suggest the pathway arising in the SCN exerts an excitatory influence on VMH neurons involved in the control of BAT function.     

Effects of unilateral and bilateral labyrinthectomy on rat postural muscle properties: the soleus

The aim of our study was to determine whether the suppression of the vestibular inputs could have effects on the soleus muscle properties similar to the modifications observed after an episode of microgravity. The inner ear lesion was performed by surgical labyrinthectomy. Twenty-nine male Wistar rats were used for this study and were divided into three experimental groups: control (CONT, n=7), unilateral labyrinthectomized (UL, n=14) and bilateral labyrinthectomized (BL, n=8). Mechanical, histochemical and electrophoretic parameters were determined 17 days after the operation. Furthermore, electromyographic (EMG) activity of the soleus muscle was examined at 1 h, 1 day and 17 days. Our results showed that UL and BL groups did not present any sign of muscle atrophy when compared to CONT group. However, the contractile and phenotypical characteristics of UL and BL soleus muscles revealed that the muscle evolved from slow toward a slower type. This transition was correlated with a more tonic EMG activity pattern. To conclude, our data demonstrated that soleus muscle transformations observed after microgravity (muscle atrophy, slow-to-fast transition, phasic EMG activity) were not directly the consequence of a vestibular silence.     

Hypothalamic vasopressin gene expression increases in both males and females postpartum in a biparental rodent

In previous studies, the closely related neuropeptide hormones oxytocin and vasopressin have been implicated in the central mediation of parental behaviour. Several studies in rats and sheep have demonstrated a role for oxytocin in the initiation of maternal behaviour. Recently, a few studies in a biparental species, the prairie vole (Microxytocinus ochrogaster) have suggested that vasopressin is important for paternal care. The present study investigated this latter possibility by measuring changes in vasopressin and oxytocin hypothalamic gene expression 1 day and 6 days following parturition in prairie voles which show paternal care and in montane voles (M. montanus) which lack paternal care. In prairie voles, vasopressin gene expression increased in both males and females postpartum, relative to sexually naive controls. In the non-paternal montane vole, no change in vasopressin gene expression was observed in either sex. In contrast to this species difference in vasopressin gene expression, hypothalamic oxytocin gene expression increased in both prairie and montane vole females, but not in males of either species. To augment measures of gene expression, we assessed vasopressin (V1a) and oxytocin receptor binding in both species. Although forebrain vasopressin V1a receptor binding was not altered following parturition in either species, oxytocin receptor binding increased in the ventromedial nucleus of the hypothalamus in females, but not males, in both prairie and montane voles. In summary, vasopressin gene expression increases in both males and females postpartum in a biparental species and oxytocin gene expression and receptor binding increase selectively in females. These results are consistent with earlier reports of a role for vasopressin in paternal care and for oxytocin in maternal behaviour.     

Accelerated norepinephrine turnover in peripheral tissues after ventromedial hypothalamic stimulation in rats

To obtain evidence for a functional connection between the ventromedial hypothalamic nucleus (VMH) and the sympathetic nervous system, effects of electrical stimulation of the VMH, the lateral hypothalamic area (LH) and the paraventricular hypothalamic nucleus (PVN) on norepinephrine (NE) turnover in the heart, liver, pancreas, spleen, submandibular gland and the interscapular brown adipose tissue were examined in anesthetized rats. Stimulation of the VMH elicited a 3-8-fold increase in the rate of NE turnover in all organs examined, whereas stimulation of the LH or the PVN had no appreciable effects. The effect of VMH stimulation was abolished after sympathetic ganglionic blockade with hexamethonium. Epinephrine turnover in the adrenal gland was accelerated by stimulation of not only the VMH but also the LH. It was concluded that the VMH is intimately associated with sympathetic facilitation in peripheral tissues.     

Sympathetic influence on sodium-potassium activated adenosine triphosphatase activity of rabbit and rat choroid plexus

Ouabain-sensitive Na+-K+-ATPase was measured spectrophotometrically in the lateral choroid plexuses of rabbit and rat. In the rabbit, a significant increase in the enzyme activity was seen at one week after unilateral sympathectomy (removal of the superior cervical ganglion), but not at three days or two weeks postoperatively, as compared with the intact, contralateral plexus. Unilateral sympathetic denervation of the rat's choroid plexus induced a nearly 40% decrease in Na+-K+-ATPase activity at 6 days after the operation, while no effect was seen after 12 days. The results agree with a local sympathetic inhibition of CSF production in rabbit (corresponding studies on rat have not been performed), and favor the assumption that the adrenergic nerves in the choroid plexus mediate direct effects on transport functions in the plexus epithelium.     

Active sodium-potassium transports in skeletal muscles of deoxycorticosterone hypertensive rats

CNS-induced suppressions of active Na⁺,K⁺ transport was investigated in both ‘tonic’ muscle, soleus (SOL), and ‘twitch’ muscle, extensor digitorum longus (EDL) of deoxycorticosterone acetate (DOCA) hypertensive rats. There was a marked K⁺ loss and Na⁺ accumulation in the skeletal and smooth muscles of DOCA hypertensive rats. The cellular K⁺ loss was in the order of SOL > EDL > diaphragm > intestine > aorta. However, liver, kidney and CNS organs such as cerebrum, cerebellum and medulla oblongata were spared from this K⁺ fall. Sciatic nerve sectioning or cervical transection activated the active Na⁺, K⁺ transport in SOL during DOCA hypertension but inhibited further the pump activity in EDL. The application of tetrodotoxin on the sciatic nerve also activated the Na⁺, K⁺ transport in SOL but inhibited the transport in EDL. The facilitatory effect of denervation on the pump activity in SOL was abolished by pretreatment with ouabain. Injection of curare had no effect on Na⁺ and K⁺ contents in both SOL and EDL. These results indicate that the CNS is involved differently on the neural regulations of the active Na⁺, K⁺ transport systems in SOL and EDL of DOCA hypertensive rats.