Contribution of histamine type-1 receptor to metabolic and behavioral control of ventilation

Histaminergic neurons in the hypothalamus are well documented as being involved in the control of autonomic functions, such as the balance of energy metabolism and circadian rhythm. We tested the hypothesis that an activation of the histamine type-1 (H1) receptor is required for the control of ventilation during the course of a day in free-moving mice. Ventilation, aerobic metabolism, and electroencephalogram were measured by a whole-body-plethysmograph, a magnetic-type mass spectrometry system, and a telemetry system, respectively, in H1 receptor-knockout (H1RKO) and wild-type mice. Both genotypes showed daily oscillations in minute ventilation (V(E)) and oxygen consumption (VO(2)), with greater values during the dark period compared to the light period. In the latter, H1RKO mice showed increased V(E) and CO(2) excretion (VCO(2)) relative to wild-type mice, and V(E) was comparable to the VCO(2) increase. However, there was no change in VO(2) in H1RKO mice, suggesting that differences in VCO(2) between genotypes are responsible for differences in V(E) during the light period. During the dark period, VCO(2) was elevated in H1RKO mice compared with WT mice. Because there was no difference in V(E), the ratio of V(E) to VCO(2) was reduced in H1RKO mice. Electroencephalogram results suggested that this might be due to a depressed arousal state in H1RKO mice because the ratio of delta to theta band power spectrum densities was greater in H1RKO mice than in wild-type mice. We concluded that histamine modulates ventilation by affecting metabolism and arousal state via H1 receptors.