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The intermediolateral cell column (IML) of the spinal cord is an important area where sympathetic impulses propagate to peripheral sympathetic organs. ANG II and aldosterone are important components of the renin-angiotensin-aldosterone system (RAAS), which activate the sympathetic nervous system. Each is partly synthesized in the brain and plays a paracrine role in the regulation of blood pressure independently of RAAS in the periphery. Our purpose in the present study was to clarify the contributions of sympathetic preganglionic neurons in the IML (IML neurons) and the effects of ANG II and aldosterone on the sympathetic nervous system. To examine responses to ANG II and aldosterone, we intracellularly recorded 104 IML neurons using a whole cell patch-clamp technique in spinal cord slice preparations. IML neurons were classified into two types: silent and firing. Both neuron types were significantly depolarized by ANG II, and candesartan inhibited this depolarization. After pretreatment with TTX, firing neurons (but not silent neurons) were significantly depolarized by ANG II. Aldosterone significantly increased the number of excitatory postsynaptic potentials (EPSPs) in both neuron types, but this response disappeared after pretreatment with TTX. ANG II and aldosterone had no synergistic effects on the IML neurons. The silent neurons had large cell soma, and many more dendrites than the firing neurons. These results suggest that ANG II acts presynaptically and postsynaptically in IML neurons, while aldosterone acts mainly presynaptically. Thus, the physiological effects of these substances are likely to be transmitted via specific membrane receptors of IML and/or presynaptic neurons. sympathetic preganglionic neuron; intermediolateral cell column

The dorsomedial medulla oblongata (DMM) includes the solitary tract nucleus and the hypoglossal nucleus, to which 5-HT neurons project. Effects of 5-HT in the DMM on ventilatory augmentation and airway dilation are mediated via 5-HT2 receptors, which interact with the C[O.sub.2] drive. The interaction may elicit cycles between hyperventilation with airway dilation and hypoventilation with airway narrowing. In the present study, effects of 5-HT2 receptors in the DMM on hypoxic ventilatory and airway responses were investigated, while 5-HT release in the DMM was monitored. Adult male mice were anesthetized, and then a microdialysis probe was inserted into the DMM. The mice were placed in a double-chamber plethysmograph. After recovery from anesthesia, the mice were exposed to hypoxic gas (7% [O.sub.2] in [N.sub.2]) for 5 rain with or without a 5-HT2 receptor antagonist (LY-53857) perfused in the DMM. 5-HT release in the DMM was increased by hypoxia regardless of the presence of LY-53857. Immediate onset and the peak of initial hypoxic hyperventilatory responses were delayed. Subsequent ventilatory decline and airway dilation during initial hypoxic hyperventilation were suppressed with LY-53857. These results suggest that 5-HT release increased by hypoxia acts on 5-HT2 receptors in the DMM, which contributes to the immediate onset of initial hypoxic hyperventilation, airway dilation, and subsequent ventilatory decline. Hypoxic ventilatory and airway responses mediated via 5-HT2 receptors in the DMM may play roles in immediate rescue and defensive adaptation for hypoxia and may be included in periodic breathing and the pathogenesis of obstructive sleep apnea. serotonin; hypoglossal nucleus; airway resistance; solitary tract nucleus; respiration

Respiratory patterns are influenced and altered by various emotional changes. In the present study, we investigated how respiratory patterns differ from individual to individual during quiet breathing. We examined the State-Trait Anxiety Inventory and various respiratory parameters in 16 healthy male subjects. Tidal volume was significantly larger and respiratory rate (RR) was significantly higher in both the higher trait (HT) and higher state (HS) anxiety groups compared to the lower trait and lower state anxiety groups. Inspiratory (T.sub.I) and expiratory time (T.sub.E) was significantly shorter in both the HT and HS anxiety groups. There was no significant difference in minute ventilation between these two groups. End-tidal CO.sub.2%, heart rate, and oxygen uptake ([formula omitted]) also showed no significant differences. V.sub.T showed a negative correlation and RR showed a positive correlation with trait scores. T.sub.I and T.sub.E showed a negative correlation with trait anxiety scores. However, no other respiratory parameter showed any correlation. These results suggest that the respiratory rhythm reflected by RR is affected by the activity generated in the higher center in accordance with the level of trait anxiety during quiet breathing in awake humans. Keywords: STAI, Respiratory rate, Trait anxiety, Quiet breathing, Author(s): Akae Kato[sup.1], Koki Takahashi[sup.1] and Ikuo Homma[sup.1] Introduction It is well known that the main function of breathing is to inhale oxygen and expire carbon dioxide for maintaining life. [...]

Ventilation oscillates throughout a day in parallel with oscillations in metabolic rate. Histamine affects ventilation and the balance of the energy metabolism via H1 receptors in the brain. We tested the hypothesis that the ventilatory response to hypoxia varies between light and dark periods and that histamine H1 receptors are required for the circadian variation, using wild-type (WT) and histamine H1 receptor knockout (H1RKO) mice. Mice were exposed to hypoxic gas (7% [O.sub.2] + 3% [CO.sub.2] in [N.sub.2]) during light and dark periods. Ventilation initially increased and then declined. In WT mice, minute ventilation ([V.sub.E]) during hypoxia was higher in the dark period than in the light period, which was an upward shift along with the baseline ventilation. Hypoxia decreased the metabolic rate, whereas [O.sub.2] consumption ([VO.sub.2]) and [CO.sub.2] excretion were higher in the dark period than in the light period. However, in H1RKO mice, changes in VE during hypoxia between light and dark periods were minimal, because [V.sub.E] was increased relative to [VO.sub.2], particularly in the light period. In H1RKO mice, the H[CO.sub.3] concentration and base excess values were increased in arterial blood, and the level of ketone bodies was increased in the serum, indicating that metabolic acidosis occurred. Respiratory compensation takes part in the [V.sub.E] increase relative to [Vo.sub.2] during hypoxia. These results suggested that changes in [V.sub.E] during hypoxia vary between light and dark periods and that H1 receptors play a role in circadian variation in VE through control of the acid-base status and metabolism in mice. H1 receptor knockout mice; hypoxia; ventilation; metabolism; circadian variation

5-HT2 receptor activity in the hypoglossal nucleus and hypercapnia is associated with airway dilation. 5-HT neurons in the medullary raphe and hypercapnia are responsible for tidal volume change. In this study, the effects of 5-HT2 receptors in the dorsomedial medulla oblongata (DMM), which receives projections from the medullary raphe, and hypercapnia on airway resistance and respiratory variables were studied in mice while monitoring 5-HT release in the DMM. A microdialysis probe was inserted into the DMM of anesthetized adult mice. Each mouse was placed in a double-chamber plethysmograph. After recovery from anesthesia, the mice were exposed to stepwise increases in C[O.sub.2] inhalation (5%, 7%, and 9% C[O.sub.2] in [O.sub.2]) at 8-min intervals with a selective serotonin reuptake inhibitor, fluoxetine, or fluoxetine plus a 5-HT2 receptor antagonist, LY-53857 in the DMM. In response to fluoxetine plus LY-53857 coperfusion, specific airway resistance was increased, and tidal volume and minute ventilation were decreased. C[O.sub.2] inhalation with fluoxetine plus LY-53857 coperfusion in the DMM largely decreased airway resistance and additively increased minute ventilation. Thus, 5-HT2 receptor activity in the DMM increases basal levels of airway dilation and ventilatory volume, dependent on central inspiratory activity and the volume threshold of the inspiratory off-switch mechanism. Hypercapnia with low 5-HT2 receptor activity in the DMM largely recovers airway dilation and additively increases ventilatory volume. Interaction between 5-HT2 receptor activity in the DMM and C[O.sub.2] drive may elicit a cycle of hyperventilation with airway dilation and hypoventilation with airway narrowing. serotonin; hypoglossal nucleus; airway resistance; solitary tract nucleus; respiration

The purpose of this study was to test whether chronically enhanced [O.sub.2] delivery to tissues, without arterial hyperoxia, can change acute ventilatory responses to hypercapnia and hypoxia. The effects of decreased hemoglobin (Hb)-[O.sub.2] affinity on ventilatory responses during hypercapnia (0, 5, 7, and 9% C[O.sub.2] in [O.sub.2]) and hypoxia (10 and 15% [O.sub.2] in [N.sub.2]) were assessed in mutant mice expressing Hb Presbyterian (mutation in the [beta]-globin gene, [beta]108 Asn [right arrow] Lys). [O.sub.2] consumption during normoxia, measured via open-circuit methods, was significantly higher in the mutant mice than in wild-type mice. Respiratory measurements were conducted with a whole body, unrestrained, single-chamber plethysmograph under conscious conditions. During hypercapnia, there was no difference between the slopes of the hypercapnic ventilatory responses, whereas minute ventilation at the same levels of arterial PC[O.sub.2] was lower in the Presbyterian mice than in the wild-type mice. During both hypoxic exposures, ventilatory responses were blunted in the mutant mice compared with responses in the wild-type mice. The effects of brief hyperoxia exposure (100% [O.sub.2]) after 10% hypoxia on ventilation were examined in anesthetized, spontaneously breathing mice with a double-chamber plethysmograph. No significant difference was found in ventilatory responses to brief hypoxia between both groups of mice, indicating possible involvement of central mechanisms in blunted ventilatory responses to hypoxia in Presbyterian mice. We conclude that chronically enhanced [O.sub.2] delivery to peripheral tissues can reduce ventilation during acute hypercapnic and hypoxic exposures. hyperoxia; hypoxia; hypercapnia; tissue; breathing