Air Quality Criteria for Lead Volume II of II - (NEPIS)(EPA) - US ...

AX5-62
Table AX5-5.1 (cont’d). In Vivo and In Vitro Studies of the Effects of Lead Exposure on Production and Metabolism of
Reactive Oxygen Species, Nitric Oxide, and Soluble Guanylate Cyclease
Reference
Vaziri et al.
(1999b)
Vaziri et al.
(2001)
Vaziri and
Ding (2001)
Pb Exposure Measured Parameters
Species/
Tissue Age/Weight n Dosage Duration Pb Level CVS Other Interventions Results
Male SD
rats
Male SD
rats
Human
coronary
endothelial
cells
200 g 6 per group
per time point
Pb-acetate,
100 ppm in
water
3 mo 8.2 ± .8 and
10.8 ± 1 µg
per g. Kidney
tissue in
untreated and
antiox-treated
groups
BP Aorta and
kidney eNOS
protein
abundance, Ur
NO2 + NO
200 g 6 per group Pb acetate 3 mo N/A BP Aorta, heart,
kidney and brain
NOS isoforms,
urine NO2 +
NO3
N/A $4 per
experiment
0 and 1 ppm
Pb acetate
24 hrs w/Pb
or Na acetate
followed
by 24 hrs
w/tempol or
vehicle
1 ppm medium N/A eNOS
expression
Subgroups
treated with highdose
vitamin E
Subgroups
studied after 2
wks of Rx
w/tempol and
those studied 2
wks after
cessation of
tempol Rx
Co-treatment
•
w/O2 scavenger,
tempol
Pb exposure resulted in a
time-dependent rise in
BP, aorta and kidney
eNOS and iNOS. This
was associated w/a
paradoxical fall in NO
availability (Ur NO2 ±
NO3). Antioxidant Rx
attenuated upregulation
of iNOS and eNOS and
raised NO availability.
Pb exposure resulted in
rises in BP, eNOS, iNOS
and nNOS in the tested
tissues + ↓urine NOx.
Tempol administration
attenuated HTN, reduced
NOS expressions and
increased urine NOx.
The effects of tempol
disappeared within 2 wks
of its discontinuation.
Pb exposure for 48 hr
upregulated eNOS
expression. Co-treatment
w/ tempol resulted in
dose-dependent reversal
of Pb-induced
upregulation of eNOS
but had no effect on
control cells.