Background. We have recently found evidence for increased reactive oxygen s
pecies (ROS) in rats with lead-induced hypertension. We hypothesized that i
ncreased ROS activity may contribute to hypertension by enhancing inactivat
ion of nitric oxide (NO) in this model.
Methods. Rats were treated for 12 weeks with either lead acetate (100 p.p.m
.) alone (Pb group) or lead acetate plus vitamin E-fortified food (5000 U/k
g rat chow, Pb + E group). The control animals were fed either regular rat
chow or a vitamin E-fortified diet. Blood pressure, creatinine clearance, a
nd urinary excretion of stable NO metabolites (NOx) were monitored, and pla
sma and tissue abundance of nitrotyrosine, which is the footprint of NO oxi
dation by ROS, were determined.
Results. The Pb group showed a marked rise in blood pressure, a significant
increase in plasma and kidney, heart, liver, and brain nitrotyrosine abund
ance, and a substantial fall in urinary NOx excretion. Concomitant administ
ration of high-dose vitamin E in the Pb + E group ameliorated hypertension
and normalized both urinary NOx excretion and tissue nitrotyrosine without
altering tissue lead content. However, vitamin E supplementation had no dis
cernible effect on either blood pressure or nitrotyrosine abundance in the
normal controls.
Conclusions. These findings point to enhanced ROS-mediated inactivation and
sequestration of NO, which can potentially contribute to hypertension, tis
sue damage, and reduced urinary NOx excretion in rats with lead-induced hyp
ertension. The beneficial effects of high-dose vitamin E on blood pressure,
tissue nitrotyrosine burden, and urinary NOx excretion support the role of
increased ROS activity in the pathogenesis of these abnormalities in this
model.