In 10 experiments on 3 conscious dogs exercising on a treadmill, we studied the effect of ozone on base-line ventilation and on ventilatory responses to inhaled bronchoconstrictor drugs. Prior to ozone exposure, inhalation of histamine diphosphate aerosol (1%; 5 breaths) increased respiratory frequency (f) by 86 +/- 11% (mean +/- SE), and inhalation of prostaglandin F2 alpha (PGF2 alpha) aerosol (0.1%; 5 breaths) increased f by 74 +/- 16%. Immediately after ozone exposure %0.65 ppm; 2 h), steady-state base line f was increased by 120 +/- 18% and tidal volume (VT) was decreased by 43 +/- 5%. When conduction in the cervical vagus nerves (that were exteriorized permanently in skin loops) was blocked by cooling, these changes caused by ozone were abolished (P greater than 0.05). The increased responses to both histamine and PGF2 alpha aerosols after ozone were unaffected by pretreatment of isoproterenol aerosol (0.5%; 15 breaths), but were completely abolished by vagal cooling. Our studies indicate that ozone-induced rapid, shallow breathing and the increased ventilatory responses to inhaled histamine and PGF2 alpha aerosols are mediated through vagal afferent pathways.

The acute ventilatory response to spontaneously inhaled cigarette smoke (750 ml, 10% concentration) was studied in 92 experiments on 6 awake resting dogs. Upon the first or second breath of smoke inhalation, either an apnea or an augmented breath was elicited consistently in each dog, and a hyperpnea occurred subsequently. Minute ventilation (VE) increased from a base line of 3.2 to a peak of 23.9 l/min at 8.3 s (mean values) after the smoke was completely inhaled and returned toward base line in 1-3 min. Cold blocking of both vagi (exteriorized in skin loops) eliminated the initial change in breathing pattern but did not significantly reduce the delayed hyperpnea. Denervation of carotid body chemoreceptors alone abolished 71.5% of the increase in VE induced by cigarette smoke. These results suggest that the apnea or augmented breath immediately following the smoke inhalation is mediated through vagal afferents, whereas the delayed hyperpnea results primarily from the stimulation of carotid body chemoreceptors, presumably by the absorbed nicotine.