Hyperoxia impairs airway relaxation in immature rats via a cAMP-mediated mechanism.
Hyperoxic exposure enhances airway reactivity in newborn animals, possibly due to altered relaxation. We sought to define the role of prostaglandinand nitric oxide-mediated mechanisms in impaired airway relaxation induced by hyperoxic stress. We exposed 7-day-old rat pups to either room air or hyperoxia (>95% O2) for 7 days to assess airway relaxation and cAMP and cGMP production after electrical field stimulation (EFS). EFS-induced relaxation of preconstricted trachea was diminished in hyperoxic vs. normoxic animals (P < 0.05). Indomethacin (a cyclooxygenase inhibitor) reduced EFS-induced airway relaxation in tracheae from normoxic (P < 0.05), but not hyperoxic, rat pups; however, in the presence of NG-nitro-L-arginine methyl ester (a nitric oxide synthase inhibitor) EFS-induced airway relaxation was similarly decreased in tracheae from both normoxic and hyperoxic animals. After EFS, the increase from baseline in the production of cAMP was significantly higher in tracheae from normoxic than hyperoxic rat pups, and this was accompanied by greater prostaglandin E2 release only in the normoxic group. cGMP production after EFS stimulation did not differ between normoxic and hyperoxic groups. We conclude that hyperoxia impairs airway relaxation in immature animals via a mechanism primarily involving the prostaglandin-cAMP signaling pathway with an impairment of prostaglandin E2 release and cAMP accumulation.
Mhanna
Maroun J
MJ
Department of Pediatrics, MetroHealth Medical Center, 2500 MetroHealth Dr., Cleveland, OH 44109, USA. mmhanna@metrohealth.org
Haxhiu
Musa A
MA
Jaber
Marwan A
MA
Walenga
Ronald W
RW
Chang
Chang-Ho
CH
Liu
Shijian
S
Martin
Richard J
RJ
D000818:Animals; D000831:Animals, Newborn; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D018496:Hyperoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D009126:Muscle Relaxation; D009130:Muscle, Smooth / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea / Q000503:physiopathology*
D000242:Cyclic AMP; D006152:Cyclic GMP; D015232:Dinoprostone