Impaired ventilation and metabolism response to hypoxia in histamine H1 receptor-knockout mice

Ishiguro, Takashi; Iwase, Michiko; Kanamaru, Mitsuko; Izumizaki, Masahiko; Ohshima, Yasuyoshi; Homma, Ikuo

doi:10.1016/j.resp.2006.01.017

Cited by 22 publications

(39 citation statements)

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“…Second, a blunted HVD might be related to a delayed peak and sustained levels of E in H1RKO mice. In an earlier study using hypoxic gas containing 3% CO 2 , HVD was blunted during a 10-min exposure in H1RKO mice [7]. Blunted HVD is accompanied by a reduction of the metabolic rate decrease with an identical ratio of E /O 2 consumption [7], suggesting that E is adequately controlled in accordance with metabolic demand in H1RKO mice.…”

Section: Ve (Ml/min/10g Bw)mentioning

confidence: 86%

“…In an earlier study using hypoxic gas containing 3% CO 2 , HVD was blunted during a 10-min exposure in H1RKO mice [7]. Blunted HVD is accompanied by a reduction of the metabolic rate decrease with an identical ratio of E /O 2 consumption [7], suggesting that E is adequately controlled in accordance with metabolic demand in H1RKO mice. In poikilocapnic hypoxia, hyperventilation surely occurs by 20 min after hypoxic gas exposure, and hypocapnia changes ventilatory control based on metabolic demand.…”

Section: Ve (Ml/min/10g Bw)mentioning

confidence: 86%

“…In earlier studies, we observed biphasic ventilatory responses to normocapnic hypoxia in mice. We added 3% CO 2 to the hypoxic gas to maintain a constant level of arterial PCO 2 (PaCO 2 ) [2,4,7]; this prevents hypocapnia induced by hypoxic hyperventilation [8]. Indeed, our previous blood gas analyses in mice showed PaCO 2 levels of 36-39 mmHg at 10 min after 7% O 2 inhalation adding 3% CO 2 [4, 9], but 19 mmHg at the same time after 7% O 2 inhalation [10].…”

mentioning

confidence: 99%

“…We focused on the ventilatory responses to poikilocapnic hypoxia in which the PaCO 2 level decreased over time, and compared these responses to those of normocapnic hypoxia. Circadian variation has also been observed in ventilatory response to normocapnic hypoxia [4], but ventilatory responses to poikilocapnic hypoxia remain unknown.Histamine H1 receptors in the brain are involved in hypoxic ventilatory control, specifically the HVD accompanying decrease in the metabolic rate [7]. Histamine is known as a functional neuromodulator that tonically acts on the respiratory neuron network and is further activated during hypoxia [14].…”

mentioning

confidence: 99%

“…Histamine H1 receptors in the brain are involved in hypoxic ventilatory control, specifically the HVD accompanying decrease in the metabolic rate [7]. Histamine is known as a functional neuromodulator that tonically acts on the respiratory neuron network and is further activated during hypoxia [14].…”

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confidence: 99%

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Time-Dependent Ventilatory Response to Poikilocapnic Hypoxia during Light and Dark Periods and the Role of Histamine H1 Receptors in Mice

et al. 2008

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Abstract:We tested the hypothesis that the biphasic ventilatory response to poikilocapnic hypoxia shows circadian variation and contribution of histamine H1 receptors in mice. Initial increases in ventilation were augmented during dark periods. H1 receptors had no major relationship with circadian variation, but affected the declined phase.Key words: histamine, ventilation, circadian variation.Ventilation endogenously oscillates throughout the day, similar to metabolism and other physiological variables [1,2]. In nocturnal animals such as rodents, ventilation and metabolism are higher in the dark period than in the light one. These circadian variations can be caused by neural inputs from the circadian pacemaker located in the suprachiasmatic nuclei, or by indirect influences on ventilatory control via the circadian rhythms of other variables [3]. Recently, the ventilatory response to hypoxia was also found to vary between light and dark periods in mice [4].Hypoxic gas inhalation causes time-dependent ventilatory responses under limited oxygen availability [5]. These responses involve an initial increase based on peripheral chemoreceptor afferents activated by hypoxia and a subsequent decline accompanied by a decrease of the metabolic rate. This biphasic ventilatory response is observed in conscious adult animals; the subsequent decline is called the "hypoxic ventilatory decline" (HVD) (reviewed by Neubauer et al. [6]). In earlier studies, we observed biphasic ventilatory responses to normocapnic hypoxia in mice. We added 3% CO 2 to the hypoxic gas to maintain a constant level of arterial PCO 2 (PaCO 2 ) [2,4,7]; this prevents hypocapnia induced by hypoxic hyperventilation [8]. Indeed, our previous blood gas analyses in mice showed PaCO 2 levels of 36-39 mmHg at 10 min after 7% O 2 inhalation adding 3% CO 2 [4, 9], but 19 mmHg at the same time after 7% O 2 inhalation [10]. However, hypoxic gas inhalation adding 3% CO 2 , augments the initial increase because of the activation of the chemoreceptor afferents responsible for changes in both PaO 2 and PaCO 2 [11]. Increased PaCO 2 enhances carotid body activity by augmenting the Ca 2+ current in glomus cells [12]. Meanwhile, hypoxia and an inhibitor of oxidative phosphorylation increase the chemosensory responses to CO 2 [11,13]. These observations show that hypoxic ventilatory responses may be influenced by additional CO 2 through a chemosensory pathway. Therefore an investigation using hypoxic gas inhalation without adding CO 2 is needed, especially to examine the chemosensory response profile. We focused on the ventilatory responses to poikilocapnic hypoxia in which the PaCO 2 level decreased over time, and compared these responses to those of normocapnic hypoxia. Circadian variation has also been observed in ventilatory response to normocapnic hypoxia [4], but ventilatory responses to poikilocapnic hypoxia remain unknown.Histamine H1 receptors in the brain are involved in hypoxic ventilatory control, specifically the HVD accompanying decrease in the metabolic rat...

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Section: Ve (Ml/min/10g Bw)mentioning

confidence: 86%

Section: Ve (Ml/min/10g Bw)mentioning

confidence: 86%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Time-Dependent Ventilatory Response to Poikilocapnic Hypoxia during Light and Dark Periods and the Role of Histamine H1 Receptors in Mice

et al. 2008

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Circadian Changes in Respiratory Responses to Acute Hypoxia and Histamine H1 Receptors in Mice

Iwase

Ohshima

Izumizaki

et al. 2009

Advances in Experimental Medicine and Biology

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Central histamine has crucial roles in circadian rhythm, ventilation, and the balance of energy metabolism via H1 receptors. We focused on the variation in ventilatory responses to hypoxia between light and dark periods, and the requirement of histamine H1 receptors for the circadian variation, using wild-type (WT) and histamine H1 receptor-knockout (H1RKO) mice. In WT mice, minute ventilation (V(E)) during hypoxia was higher in the dark period than in the light period. In H1RKO mice, changes in V(E) between photoperiods were minimal because V(E) increased relative to VO(2) (particularly in the light period). H1RKO mice showed metabolic acidosis, and increased levels of ketone bodies in blood during the light period. These data suggested that changes in V(E) during hypoxia vary between light and dark periods, and that H1 receptors have a role in the circadian variation in V(E) through control of acid-base status and metabolism in mice.

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Effects of fasting on hypoxic ventilatory responses and the contribution of histamine H1 receptors in mice

et al. 2010

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We tested the hypothesis that fasting affects hypoxic ventilatory responses through metabolic changes via histamine H1 receptors. Wild-type (WT) and histamine H1 receptor knockout (H1RKO) mice were studied in fed and fasted states. In the fed WT, hypoxic-gas exposure elicited an increase and a subsequent decline in ventilation (hypoxic ventilatory decline or HVD). HVD was influenced by fasting in breathing pattern with metabolic rate. Fasting elicited hypoglycemia, a drop in R, and increases in free fatty acid and ketone bodies in the serum. In H1RKO, HVD was blunted in the fed state, but it appeared in the fasted state. There was a minimal drop in R following fasting and a low triglyceride concentration. Thus, fasting affects HVD through a change in energy mobilization from glucose to lipid metabolism. Histamine H1 receptors are involved in HVD during fed and fasted states, resulting in adaptation to the environmental conditions.

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Impaired ventilation and metabolism response to hypoxia in histamine H1 receptor-knockout mice

Cited by 22 publications

References 39 publications

Time-Dependent Ventilatory Response to Poikilocapnic Hypoxia during Light and Dark Periods and the Role of Histamine H1 Receptors in Mice

Time-Dependent Ventilatory Response to Poikilocapnic Hypoxia during Light and Dark Periods and the Role of Histamine H1 Receptors in Mice

Circadian Changes in Respiratory Responses to Acute Hypoxia and Histamine H1 Receptors in Mice

Effects of fasting on hypoxic ventilatory responses and the contribution of histamine H1 receptors in mice

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