Abstract
Ventilatory responses to acute hypoxia (HVR) are modulated by histamine H1 receptors via changes in the metabolic rate. Hypothalamic histamine contributes to an energy supply balance to the brain during starvation. We tested the hypothesis that HVR varies with feeding states and that histamine H1 receptors are also involved in the responses after fasting. Wild-type (WT) and histamine H1 receptor knockout (H1RKO) mice were exposed to hypoxic gas (7% O2 + 3% CO2 in N2) for 20 min in a 12 h fasted state and in a fed state. In WT mice, HVR in the fed state showed an initial increase and then a sequential decline (hypoxic ventilatory decline, HVD); whereas, HVR in the fasted state was initially increased and thereafter maintained. A smaller reduction in O2 consumption (VO2) during hypoxia and a lower respiratory exchange ratio (R) were observed in the fasted state than in the fed one, suggesting that fasting diminishes HVD along with undamped VO2 because of a predominant lipid metabolism. In H1RKO mice, HVR in the fed state showed an initial increase and its maintenance throughout hypoxia; conversely, HVR in the fasted state showed an initial increase and HVD. VO2 during hypoxia was not significantly different between fed states, although CO2 excretion was lower in the fasted state than in the fed one. These results suggested that HVR is affected by fed states because of a change in the balance between lipid and glucose metabolisms, and that histamine H1 receptors may be involved in the HVR depending on the fed states. [J Physiol Sci. 2008;58 Suppl:S118]
