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

The role of central histamine in the hypoxic ventilatory response was examined in conscious wild-type (WT) and histamine type1 receptor-knockout (H1RKO) mice. Hypoxic gas (7% O2 and 3% CO2 in N2) exposure initially increased and then decreased ventilation, referred to as hypoxic ventilatory decline (HVD). The initial increase in ventilation did not differ between genotypes. However, H1RKO mice showed a blunted HVD, in which mean inspiratory flow was greater than that in WT mice. O2 consumption (V˙O2) and CO2 excretion were reduced 10 min after hypoxic gas exposure in both genotypes, but V˙O2 was greater in H1RKO mice than in WT mice. The ratio of minute ventilation to V˙O2 during HVD did not differ between genotypes, indicating that ventilation is adequately controlled according to metabolic demand in both mice. Peripheral chemoreceptor sensitivity did not differ between genotypes. We conclude that central histamine contributes via the H1 receptor to changes in metabolic rate during hypoxia to increase HVD in conscious mice.