[Involvement of cholinergic mechanism in respiratory chemosensitivity to CO2 in humans]

In an attempt to elucidate the role of cholinergic mechanism in respiratory chemosensitivity to CO2 in humans, we examined 17 healthy male volunteers for ventilatory responses to hyperoxic progressive hypercapnia and isocapnic progressive hypoxia on three separate days in a randomized, double-blind fashion. Pirenzepine, a M1 muscarinic antagonist which does not cross the blood-brain barrier, biperiden, another M1 muscarinic antagonist which is expected to penetrate into the central nervous system, or placebo was intravenously preinjected before the measurement of ventilatory responses. There were no significant differences in the mean magnitude of ventilatory responses among the three experimental days. However, despite the poor correlation between the magnitude of ventilatory response to hypercapnia in the placebo and pirenzepine studies, there was a significant correlation between them when the value in the pirenzepine study was expressed as % of control, value i.e., subjects with greater hypercapnic ventilatory response in the placebo study showed greater declines with biperiden. Since these relations were seen only for the ventilatory response to hypercapnia with biperiden, we suggest that a cholinergic mechanism, particularly the M1 muscarinic receptor, may be involved in chemoreception to CO2 in the central nervous system and constitute the neurochemical background for the interindividual variation in hypercapnic ventilatory response in humans.