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Hypertension. 1999 Oct;34(4 Pt 1):558-62.

Nitric oxide synthase expression in the course of lead-induced hypertension.

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  • 1Division of Nephrology and Hypertension, Department of Medicine, University of California, Irvine, Calif, USA.


We recently showed elevated reactive oxygen species (ROS), reduced urinary excretion of NO metabolites (NOx), and increased NO sequestration as nitrotyrosine in various tissues in rats with lead-induced hypertension. This study was designed to discern whether the reduction in urinary NOx in lead-induced hypertension is, in part, due to depressed NO synthase (NOS) expression. Male Sprague-Dawley rats were randomly assigned to a lead-treated group (given lead acetate, 100 ppm, in drinking water and regular rat chow), a group given lead and vitamin E-fortified chow, or a normal control group given either regular food and water or vitamin E-fortified food for 12 weeks. Tail blood pressure, urinary NOx excretion, plasma malondialdehyde (MDA), and endothelial and inducible NOS (eNOS and iNOS) isotypes in the aorta and kidney were measured. The lead-treated group exhibited a rise in blood pressure and plasma MDA concentration, a fall in urinary NOx excretion, and a paradoxical rise in vascular and renal tissue eNOS and iNOS expression. Vitamin E supplementation ameliorated hypertension, lowered plasma MDA concentration, and raised urinary NOx excretion while significantly lowering vascular, but not renal, tissue eNOS and iNOS expression. Vitamin E supplementation had no effect on either blood pressure, plasma MDA, or NOS expression in the control group. The study also revealed significant inhibition of NOS enzymatic activity by lead in cell-free preparations. In conclusion, lead-induced hypertension in this model was associated with a compensatory upregulation of renal and vascular eNOS and iNOS expression. This is, in part, due to ROS-mediated NO inactivation, lead-associated inhibition of NOS activity, and perhaps stimulatory actions of increased shear stress associated with hypertension.

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