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.