Skip Navigation

Publication Detail

Title: Beta-2 Adrenergic and Glucocorticoid Receptor Agonists Modulate Ozone-Induced Pulmonary Protein Leakage and Inflammation in Healthy and Adrenalectomized Rats.

Authors: Henriquez, Andres R; Snow, Samantha J; Schladweiler, Mette C; Miller, Colette N; Dye, Janice A; Ledbetter, Allen D; Richards, Judy E; Hargrove, Marie M; Williams, Wanda C; Kodavanti, Urmila P

Published In Toxicol Sci, (2018 Dec 01)

Abstract: We have shown that acute ozone inhalation activates sympathetic-adrenal-medullary and hypothalamus-pituitary-adrenal stress axes, and adrenalectomy (AD) inhibits ozone-induced lung injury and inflammation. Therefore, we hypothesized that stress hormone receptor agonists (β2 adrenergic-β2AR and glucocorticoid-GR) will restore the ozone injury phenotype in AD, while exacerbating effects in sham-surgery (SH) rats. Male Wistar Kyoto rats that underwent SH or AD were treated with vehicles (saline + corn oil) or β2AR agonist clenbuterol (CLEN, 0.2 mg/kg, i.p.) + GR agonist dexamethasone (DEX, 2 mg/kg, s.c.) for 1 day and immediately prior to each day of exposure to filtered air or ozone (0.8 ppm, 4 h/day for 1 or 2 days). Ozone-induced increases in PenH and peak-expiratory flow were exacerbated in CLEN+DEX-treated SH and AD rats. CLEN+DEX affected breath waveform in all rats. Ozone exposure in vehicle-treated SH rats increased bronchoalveolar lavage fluid (BALF) protein, N-acetyl glucosaminidase activity (macrophage activation), neutrophils, and lung cytokine expression while reducing circulating lymphocyte subpopulations. AD reduced these ozone effects in vehicle-treated rats. At the doses used herein, CLEN+DEX treatment reversed the protection offered by AD and exacerbated most ozone-induced lung effects while diminishing circulating lymphocytes. CLEN+DEX in air-exposed SH rats also induced marked protein leakage and reduced circulating lymphocytes but did not increase BALF neutrophils. In conclusion, circulating stress hormones and their receptors mediate ozone-induced vascular leakage and inflammatory cell trafficking to the lung. Those receiving β2AR and GR agonists for chronic pulmonary diseases, or with increased circulating stress hormones due to psychosocial stresses, might have altered sensitivity to air pollution.

PubMed ID: 30379318 Exiting the NIEHS site

MeSH Terms: Adrenalectomy*; Adrenergic beta-2 Receptor Agonists/pharmacology*; Animals; Bronchoalveolar Lavage Fluid/chemistry; Clenbuterol/pharmacokinetics; Corticosterone/blood; Cytokines/metabolism; Dexamethasone/pharmacology; Epinephrine/blood; G-Protein-Coupled Receptor Kinase 3/metabolism; Leukocytes/metabolism; Lung Injury/chemically induced; Lung Injury/drug therapy*; Lung Injury/metabolism; Lymphocytes/metabolism; Male; Ozone/toxicity*; Pneumonia/chemically induced; Pneumonia/drug therapy*; Pneumonia/metabolism; Random Allocation; Rats; Rats, Inbred WKY; Receptors, Glucocorticoid/agonists*; Respiratory Function Tests

Back
to Top