Lack of histamine type-1 receptors impairs the thermal response of respiration during hypoxia in mice (Mus musculus).
Thermoregulation and the hypoxic ventilatory response are modulated by histamine type-1 (H1) receptors in the brain. In this study, we tested the hypothesis that activation of H1 receptors is required for the thermal control of ventilation during normoxia and hypoxia, using conscious male wild-type and H1 receptor-knockout (H1RKO) mice (Mus musculus). Under normoxic conditions, hyperthermia (39 degrees C) decreased minute ventilation (V (E)) and oxygen consumption [Formula: see text] in both genotypes, suggesting that H1 receptors are not involved in thermal ventilatory control during normoxia. Pa(CO2) was unchanged in both hyperthermia and normothermia, suggesting that the thermal decrease in V (E) is optimized by metabolic demand. Acute hypoxic gas exposure (7% O(2)+3% CO(2) in N(2)) increased, and then decreased, V (E) in wild-type mice; this increase was augmented and sustained by hyperthermia. Hypoxic gas exposure reduced [Formula: see text] and [Formula: see text] in wild-type mice at both body temperatures; the reduced [Formula: see text] during combined hyperthermia and hypoxia was higher than during normothermia and hypoxia. In H1RKO mice, hyperthermia did not augment the V (E) response to hypoxia, and did not affect [Formula: see text] and [Formula: see text] during hypoxia. In conclusion, histamine participates in the thermal increase of ventilation during hypoxia by activating H1 receptors.
Iwase
Michiko
M
2nd Department of Physiology, Showa University School of Medicine, Tokyo 142-8555, Japan. michiko@med.showa-u.ac.jp
Izumizaki
Masahiko
M
Miyamoto
Kenichi
K
Ishiguro
Takashi
T
Kanamaru
Mitsuko
M
Homma
Ikuo
I
D000332:Aerobiosis; D000818:Animals; D001481:Basal Metabolism / Q000502:physiology; D002245:Carbon Dioxide / Q000097:blood; D006979:Hyperthermia, Induced; D000860:Hypoxia / Q000503:physiopathology*; D051379:Mice; D010100:Oxygen / Q000097:blood; D012123:Pulmonary Ventilation / Q000502:physiology*; D011969:Receptors, Histamine H1 / Q000172:deficiency*; D012119:Respiration; D013696:Temperature
D011969:Receptors, Histamine H1; D002245:Carbon Dioxide; D010100:Oxygen