Increased nitric oxide inactivation by reactive oxygen species in lead-induced hypertension

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.