Regulation of corticotropin-releasing factor receptor type 2 beta messenger ribonucleic acid in the rat cardiovascular system by urocortin, glucocorticoids, and cytokines

CRF receptor type 2 (CRF R2) messenger RNA (mRNA) expression in the rodent heart is modulated by exposure to both the bacterial endotoxin lipopolysacc haride (LPS) and glucocorticoids. In this study we examined the roles of gl ucocorticoids, cytokines, and CRF R2 beta ligands in the regulation of CRF R2 beta expression in the cardiovascular system both in vivo and in vitro. Using ribonuclease protection assays, we found that, in addition to the inj ection of LPS or corticosterone, physical restraint caused a decrease in CR F R2 beta mRNA levels in the rat heart and aorta. Adrenalectomy with cortic osterone replacement at constant levels partially blocked LPS-induced decre ases in CRF R2 beta mRNA expression in the heart. Thus, elevations of endog enous circulating corticosterone could contribute to the down-regulation of CRF R2 beta mRNA expression in heart. To identify other putative modulatin g factors, we examined CRF R2 beta expression in the aorta-derived A7R5 cel l line. Incubation with CRF R2 ligands or dexamethasone reduced CRF R2 beta mRNA levels. In addition, incubation with a variety of cytokines, proteins released during immune challenge, also reduced CRF R2 beta mRNA expression . The multifactorial regulation of CRF R2 beta mRNA expression in the cardi ovascular system may serve to limit the inotropic and chronotropic effects of CRF R2 agonists such as urocortin during prolonged physical or immune ch allenge.