Endogenous nitric oxide attenuates erythropoietin gene expression in vivo

This study aimed to investigate the role of endogenous nitric oxide (NO) in erythropoietin (EPO) gene expression in mice in vivo. For this purpose EPO mRNA was semiquantitated by ribonuclease protection assay in livers and ki dneys of three groups of mice: wild-type (wt), endothelial NO-synthase (NOS ) knockout mice (eNOS-/-), and wt treated with the NOS inhibitor N-G-nitro- L-arginine methyl ester (50 mg.kg(-1).day(-1)) for 4 days (wt+L-NAME). EPO gene expression was stimulated by normobaric hypoxia (8% O-2) Or by 0.1%, c arbon monoxide (CO) inhalation for 4 h each, or by intraperitoneal injectio n of 60 mg/kg cobaltous chloride (CoCl2) for 6 h. Renal EPO mRNA in wt incr eased 12-, 40-, and 13-fold over normoxic levels in response to hypoxia, CO and CoCl2 respectively. EPO mRNA was detectable in the livers only after C O exposure. Renal and hepatic EPO gene expression in wt+L-NAME appeared mod erately increased relative to wt with a maximal 2.5-fold enhancement after CO exposure. EPO mRNA levels in eNOS-/- mirrored those of wt+L-NAME, but th e effects were less prominent. Our data suggest that endogenous NO attenuat es EPO gene expression in mice. This effect is dependent on the rate of EPO gene induction.