Hypoxia regulates avian cardiac Arnt and HIF-1 alpha mRNA expression

The aryl hydrocarbon receptor nuclear translocator (Arnt) and hypoxia-induc ible factor (HIF)-1 alpha mediate cellular responses to hypoxia, We investi gated the ability of hypoxia to regulate Arnt and HIF-1 alpha mRNA in the h eart in vivo. We cloned avian Arnt, developed an in vivo model of chronic c ardiac hypoxia, and measured expression of cardiac Arnt and HIF-1 alpha mRN A by quantitative RT-PCR, Chronic hypoxic exposure (24 h to 15% O-2) of day 9 chick embryos resulted in a 30-fold increase in covalent binding of H-3- misonidazole, a hypoxic tissue marker, to cardiac tissue, and a a-fold indu ction of cardiac inducible nitric oxide synthase mRNA, compared to normoxic controls. In this same model, cardiac Amt mRNA expression decreased by 35% , while HIF-1 alpha mRNA expression increased 400%. These data suggest that regulation of Amt and HIF-1 alpha mRNA expression may contribute to the ph ysiological responses of the heart during prolonged hypoxia, (C) 2001 Acade mic Press.