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

Toward, Toby J. and Broadley, Kenneth John ORCID: https://orcid.org/0000-0002-3339-2050 2002. Airway function, oedema, cell infiltration and nitric oxide generation in conscious ozone-exposed guinea-pigs: effects of dexamethasone and rolipram. British Journal of Pharmacology 136 (5) , pp. 735-745. 10.1038/sj.bjp.0704764

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Abstract

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 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<0.05) elevated at 12, 24 and 48 h after ozone exposure, the 48 h influx being significantly attenuated (P<0.05) by rolipram BALF nitric oxide (NO) metabolites decreased 0.5 h after ozone exposure by 52%, recovered at 2 h and significantly increased at 12 (101%) and 24 h (127%). The elevated NO was unaffected by rolipram or dexamethasone. Lung oedema, measured from wet/dry weight differences, was significant 12, 24 and 48 h after ozone exposure, the latter being significantly attenuated (P<0.05) by rolipram and dexamethasone. Ozone exposure of guinea-pigs produced features common to COPD. Although rolipram and dexamethasone did not affect the airway function changes, they inhibited the inflammation, airway hyperreactivity and oedema.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Subjects:	R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords:	Airway hyperreactivity; corticosteroid; leukocytes; oedema; ozone; phosphodiesterase-4 inhibitor; nitric oxide; lung function
Publisher:	Wiley-Blackwell
ISSN:	0007-1188
Last Modified:	21 Oct 2022 10:29
URI:	https://orca.cardiff.ac.uk/id/eprint/40371

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