PACAP reverses airway hyperresponsiveness induced by ozone exposure in guinea pigs.
BACKGROUND
We previously demonstrated that pituitary adenylate cyclase activating peptide (PACAP) inhibits airway smooth muscle contraction and plasma extravasation.


OBJECTIVE
We thus hypothesized that PACAP may regulate airway responsiveness through these effects and examined the effects of exogenously applied PACAP on the airway hyperresponsiveness induced by ozone exposure.


METHODS
Ozone exposure was carried out in awake, spontaneously breathing guinea pigs using 3 ppm for 2 h. Airway responsiveness to histamine was determined before and 30 and 90 min after the termination of ozone exposure for 2 h in anesthetized animals. Extravasation of Evans blue was measured before and 90 min after the termination of ozone exposure. Either PACAP (10(-6) mol/kg) or vehicle was administered intravenously 60 min after exposure. The airway responsiveness was expressed as the concentration of histamine required to produce a 200% increase in total pulmonary resistance (PC(200)).


RESULTS
Ozone exposure caused a significant decrease in PC(200) (n = 5, p < 0.05) 30 min after ozone exposure which persisted 90 min thereafter, thus suggesting that ozone caused airway hyperresponsiveness. PACAP significantly suppressed the increase in airway hyperresponsiveness induced by ozone 90 min after exposure (n = 5, p < 0.05). In contrast, this peptide did not have any effect on plasma extravasation.


CONCLUSIONS
We thus conclude that PACAP decreases ozone-induced airway responsiveness, and, therefore, intravenously administered PACAP may be useful in reversing airway hyperresponsiveness.
Aizawa
H
H
Clinical Research Institute, National Fukuoka-Higashi Hospital, Koga, Japan. aizawah@fukuokae.hosp.go.jp
Shigyo
M
M
Matsumoto
K
K
Inoue
H
H
Koto
H
H
Hara
N
N
D000818:Animals; D001980:Bronchi / Q000187:drug effects*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000188:drug therapy*; D004195:Disease Models, Animal; D006168:Guinea Pigs; D007275:Injections, Intravenous; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009479:Neuropeptides / Q000008:administration & dosage*; D010126:Ozone; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011897:Random Allocation; D012016:Reference Values; D018709:Statistics, Nonparametric; D014665:Vasodilator Agents / Q000008:administration & dosage*
D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014665:Vasodilator Agents; D010126:Ozone