F. Khalilmanesh et al., EFFECT OF CHELATION TREATMENT WITH DIMERCAPTOSUCCINIC ACID (DMSA) ON LEAD-RELATED BLOOD-PRESSURE CHANGES, Environmental research, 65(1), 1994, pp. 86-99
An elevation in mean blood pressure was found in rats treated with low
lead (0.01%) for 6 months and then only water for an additional 6 mon
ths (discontinuous low lead). No change in blood pressure was found in
rats similarly treated with high lead (0.5%) (discontinuous high lead
). Administration of DMSA (0.5% in drinking water), for 5 days every 2
months following cessation of lead administration, resulted in a sign
ificant lowering of blood pressure in both groups of animals. In the l
ow-lead but not the high-lead group, this was associated with an incre
ase in plasma cyclic GMP (acting as a second messenger for endothelium
-derived relaxing factor, EDRF) and a decrease in the plasma concentra
tion of a 12-kDa hypertension-associated protein. Plasma endothelin-3
(ET-3) levels were decreased in discontinuous high-lead rats, increase
d in discontinuous low-lead rats, but were unaltered by DMSA treatment
. We infer that the elevated blood pressure in the discontinuous low-l
ead rats is related to an increase in the putative vasoconstrictors, E
T-3 and the hypertension-associated protein, without a change in the v
asodilator, EDRF. With DMSA treatment, plasma cyclic GMP in low-lead r
ats increased above normal, and the hypertension associated protein de
creased, resulting in lowered blood pressure. DMSA was shown to act as
an antioxidant in vitro. Thus the DMSA effect on plasma cGMP (EDRF) m
ay occur via a scavenging effect on EDRF-inactivating reactive oxygen
species. (C) 1994 Academic Press, Inc.