Hyperoxia impairs airway relaxation in immature rats via a cAMP-mediated mechanism

• Published in: Journal of applied physiology (1985) Vol. 96; no. 5; pp. 1854 - 1860
• Main Authors: Mhanna, Maroun J, Haxhiu, Musa A, Jaber, Marwan A, Walenga, Ronald W, Chang, Chang-Ho, Liu, Shijian, Martin, Richard J
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Physiological Soc 01.05.2004; American Physiological Society
• Subjects: Animals; Animals, Newborn; Biological and medical sciences; Cyclic AMP - metabolism; Cyclic GMP - metabolism; Dinoprostone - metabolism; Fundamental and applied biological sciences. Psychology; Hormones; Hyperoxia - physiopathology; In Vitro Techniques; Lungs; Muscle Relaxation; Muscle, Smooth - physiopathology; Nitric oxide; Rats; Rats, Sprague-Dawley; Respiratory system; Rodents; Trachea - physiopathology; Adenosine; Purine nucleoside; Rat; Rodentia; Cyclic AMP; Respiratory system; Mechanism; adenosine 3',5'-cyclic monophosphate; Respiratory tract; Relaxation; Vertebrata; Mammalia; Cyclic; Hyperoxia; guanosine 3',5'- cyclic monophosphate; Immaturity
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.01178.2002

Department of Pediatrics, 1 MetroHealth Medical Center and 2 Rainbow Babies and Children's Hospital, and 3 Department of Medicine, University Hospitals of Cleveland, Case Western Reserve University School of Medicine, Cleveland, Ohio 44109 Submitted 20 December 2002 ; accepted in final form 24 November 2003 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% O 2 ) 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 N G -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 E 2 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 E 2 release and cAMP accumulation. immaturity; adenosine 3',5'-cyclic monophosphate; guanosine 3',5'-cyclic monophosphate Address for reprint requests and other correspondence: M. J. Mhanna, Dept. of Pediatrics, MetroHealth Medical Center, 2500 MetroHealth Dr., Cleveland, OH 44109 (E-mail: mmhanna{at}metrohealth.org ).