Nd. Vaziri et Yx. Ding, Effect of lead on nitric oxide synthase expression in coronary endothelialcells - Role of superoxide, HYPERTENSIO, 37(2), 2001, pp. 223-226
Citations number
11
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Chronic exposure to low levels of lead causes hypertension (HTN) in humans
and animals. We have previously shown that increased reactive oxygen specie
s (ROS) leads to enhanced NO inactivation, depressed NO bioavailability, an
d compensatory upregulation of NO synthases (NOSs) in rats with lead-induce
d HTN. We have further demonstrated increased ROS generation with lead expo
sure in cultured endothelial cells. In the present study, we tested the eff
ect of lead (medium containing lead acetate, 1 ppm) alone and with either t
he superoxide dismutase-mimetic agent tempol or a potent antioxidant lazaro
id compound (both at 10(-8) and 10(-7) mol/L) on endothelial NOS expression
and NO production in cultured human coronary endothelial cells. Lead-treat
ed cells showed a significant upregulation of endothelial NOS (eNOS) protei
n abundance (P<0.002) and a significant increase in the production of NO me
tabolites (NO2- +NO3- =NOx, P<0.01). Cotreatment with either tempol or laza
roid abrogated the lead-induced upregulation of eNOS protein and NOx produc
tion. In contrast, tempol and lazaroid had no effect on either eNOS protein
expression or NOx production in the control cells. Thus, lead exposure upr
egulated eNOS expression in vitro, simulating the results of our previous i
n vivo studies. This phenomenon points to a direct as opposed to an indirec
t (eg, HTN-mediated) effect of lead on NO metabolism. The reversal of lead
effect by lazaroid and the cell-permeable superoxide dismutase-mimetic agen
t tempol suggests that lead exposure increases generation and/or reduces di
smutation of superoxide, which in turn promotes oxidative stress, enhances
NO inactivation, and elicits a compensatory upregulation of eNOS whose expr
ession is negatively regulated by NO.