Independent roles of beta-adrenergic and glucocorticoid receptors in systemic and pulmonary effects of ozone

Background: The release of catecholamines is preceded by glucocorticoids during a stress response. We have shown that ozone-induced pulmonary responses are mediated through the activation of stress hormone receptors. Objective: To examine the interdependence of beta-adrenergic (beta AR) and glucocorticoid receptors (GRs), we inhibited beta AR while inducing GR or inhibited GR while inducing beta AR and examined ozone-induced stress response. Methods: Twelve-week-old male Wistar-Kyoto rats were pretreated daily with saline or propranolol (PROP; beta AR-antagonist; 10 mg/kg-i.p.; starting 7-d prior to exposure) followed-by saline or dexamethasone (DEX) sulfate (GR-agonist; 0.02 mg/kg-i.p.; starting 1-d prior to exposure) and exposed to air or 0.8 ppm ozone (4 h/d x 2-d). In a second experiment, rats were similarly pretreated with corn-oil or mifepristone (MIFE; GR-antagonist, 30 mg/kg-s.c.) followed by saline or clenbuterol (CLEN; beta(2)AR-agonist; 0.02 mg/kg-i.p.) and exposed. Results: DEX and PROP + DEX decreased adrenal, spleen and thymus weights in all rats. DEX and MIFE decreased and increased corticosterone, respectively. Ozone-induced pulmonary protein leakage, inflammation and IL-6 increases were inhibited by PROP or PROP + DEX and exacerbated by CLEN or CLEN + MIFE. DEX and ozone-induced while MIFE reversed lymphopenia (MIFE > CLEN + MIFE). DEX exacerbated while PROP, MIFE, or CLEN + MIFE inhibited ozone-induced hyperglycemia and glucose intolerance. Ozone inhibited glucose-mediated insulin release. Conclusions: In summary, 1) activating beta AR, even with GR inhibition, exacerbated and inhibiting beta AR, even with GR activation, attenuated ozone-induced pulmonary effects; and 2) activating GR exacerbated ozone systemic effects, but with beta AR inhibition, this exacerbation was less remarkable. These data suggest the independent roles of beta AR in pulmonary and dependent roles of beta AR and GR in systemic effects of ozone.