Airway function, oedema, cell infiltration and nitric oxide generation in conscious ozone‐exposed guinea‐pigs: effects of dexamethasone and rolipram

• Published in: British journal of pharmacology 2002-07, Vol.136 (5), p.735-745
• Main Authors: Toward, Toby J, Broadley, Kenneth J
• Format: Article
• Language: English
• Subjects: Airway hyperreactivity; Animals; corticosteroid; Dexamethasone - pharmacology; Dexamethasone - therapeutic use; Guinea Pigs; leukocytes; lung function; Male; Neutrophil Infiltration - drug effects; Neutrophil Infiltration - physiology; nitric oxide; Nitric Oxide - metabolism; oedema; Oxidative Stress - drug effects; Oxidative Stress - physiology; ozone; Ozone - adverse effects; phosphodiesterase‐4 inhibitor; Pulmonary Disease, Chronic Obstructive - chemically induced; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Disease, Chronic Obstructive - metabolism; Pulmonary Edema - chemically induced; Pulmonary Edema - drug therapy; Pulmonary Edema - metabolism; Rolipram - pharmacology; Rolipram - therapeutic use
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0704764

The effects of ozone inhalation (90 min, 2.15±0.05 p.p.m.) and their modification by dexamethasone (20 mg kg−1) or the phosphodiesterase‐4 inhibitor, rolipram (1 mg kg−1), administered (i.p.) 24 and 0.5 h before and 24 h after ozone exposure were examined in conscious guinea‐pigs. Ozone caused an early‐phase bronchoconstriction (EPB) as a fall in specific airways conductance (sGaw) measured by whole body plethysmography, followed at 5 h by a late‐phase bronchoconstriction (LPB) and increased respiratory rate. Rolipram did not alter this profile but dexamethasone inhibited the EPB. Airway hyperreactivity to inhaled histamine (1 mM, 20 s) occurred at 0.5, 2, 12, 24 and 48 h after ozone inhalation, the 2 h change being abolished by rolipram and dexamethasone. Bronchoalveolar lavage fluid (BALF) macrophages, eosinophils and neutrophils were significantly (P