J Midorikawa, Y Kikuchi, O Taguchi, W Hida, S Okabe, T Takishima and K Shirato
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.

It is known that the ventilatory response to carbon dioxide (CO2) is increased in asthmatics with airway obstruction. Increased vagal afferent activity as well as increased airway resistance have been postulated as the causative mechanisms. However, whether increased vagal afferent activity without bronchoconstriction increases the ventilatory response to CO2 has not been investigated in humans. We examined the effects of prostaglandin E2 (PGE2) inhalation, which is known to stimulate vagal afferent receptors in the lung without an increase in airway resistance, on the respiratory response to CO2 in seven healthy male subjects. Either physiologic saline or PGE2 (100 micrograms/ml) was inhaled through a Bird nebulizer for 3 min. Twenty minutes after each inhalation, the responses of minute ventilation (VE) and occlusion pressure (P0.1) to hyperoxic hypercapnia were measured. Both the relationships between VE and P0.1 to an increase in tension of end-tidal CO2 (PETCO2) were analyzed by linear regression. Although the mean value of respiratory resistance after PGE2 (3.0 cm H2O/L/s +/- 0.4) did not differ significantly from that after saline (3.1 cm H2O/L/s +/- 0.4), inhaled PGE2 significantly increased the hypercapnic response. This result suggests that the increased vagal afferent activity per se plays an important role in increasing the hypercapnic ventilatory response in humans.