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

AX5-65
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
Khalil-
Manesh et al.
(1993b)
Marques et al.
(2001)
Farmand et al.
(2005)
Courtois et al.
(2003)
Pb Exposure Measured Parameters
Species/
Tissue Age/Weight n Dosage Duration Pb Level CVS Other Interventions Results
Male SD
rats
Male
Wistar rats
Male SD
rats
Rat
thoracic
aorta
8 wks N/A Pb acetate 100 or
5000 ppm in
water
3 mo 20 Pb acetate 5 ppm
± Vit C (3
mmol/L) in
water
200 g 8 Pb acetate 100
ppm in water
N/A 6/
experiment
1–12 mo 29 ± 4 µg/dL BP, vascular
contractility to
NE in vitro
30 days N/A BP, arch-, SNPvasorelaxation
response in aorta
rings
cGMP, ET-3, ANP — Pb caused HTN,
↓serum and urine
cGMP, ↑serum ET-3
without changing ANP
or response to NE
sGC protein mRNA
and activity.
cGMP production,
eNOS protein
3 mo N/A BP Aorta sGC, SOD,
catalase,
glutathione
peroxidase
0–1 ppm 24 hr 0–1 ppm cGMP
production
sGC expression,
superoxide
production, COX-2
CoTx with Vit C Pb caused HTN,
↓relaxation to Ach and
SNP, ↑eNOS, ↓sGC
protein mRNA and
activity. These
abnormalities were
prevented by
antioxidant Rx.
Vit C, COX-2
inhibitor
— ↓sGC, ↑CuZn SOD
activity, unchanged
catalase and GPX
activities.
Pb caused ↓sGC,
↓cGMP, ↑O2, ↑COX-2.
All abnormalities
improved by Vit C.
COX-2 inhibitor
improved sGC
expression but not O2
production.