Abstract
In order to clarify whether central histamine affects breathing pattern formation, we examined breathing patterns during hypercapnia in wild type (WT) and histamine H1 receptor knock-out (H1RKO) mice. Male WT and H1RKO mice were used at 9-10 weeks of age. Breathing pattern was measured with whole body plethysmograph during stepwise CO2 gas exposures from 3% to 9% in an unaesthetized state, which was also performed in cervical vagotomized mice after recovery of pentobarbital anesthesia. PaCO2 was determined by blood gas analysis during 5% and 9% CO2 gas exposures in a conscious state. Minute ventilation increased in proportion with a PaCO2-increase similarly in both mice; however, respiratory rate (RR) was lower and tidal volume (VT) was higher in H1RKO mice than in WT mice. The VT-inspiratory time (TI) relationship during CO2 gas exposure showed a hyperbolic curve in both mice, whereas the relationship in H1RKO mice shifted above to the right than those in WT mice. After vagotomy, the VT-TI relationship changed to a vertical line in both mice, meaning that VT increased without a change of TI. The VT-TI lines of the H1RKO mice shifted to the right of those of the WT mice. These results suggest that H1RKO mice elevated the threshold level terminating inspiration; therefore, decreased RR and increased VT were observed at the same PaCO2, which indicates that the inspiratory off-switch mechanism was altered. It is conceivable that histamine centrally affects breathing pattern formation via H1 receptors. [Jpn J Physiol 54 Suppl:S111 (2004)]
