EFFECT OF CHELATION TREATMENT WITH DIMERCAPTOSUCCINIC ACID (DMSA) ON LEAD-RELATED BLOOD-PRESSURE CHANGES

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 months (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 significant lowering of blood pressure in both groups of animals. In the low-lead but not the high-lead group, this was associated with an increase in plasma cyclic GMP (acting as a second messenger for endothelium-derived relaxing factor, EDRF) and a decrease in the plasma concentration of a 12-kDa hypertension-associated protein. Plasma endothelin-3 (ET-3) levels were decreased in discontinuous high-lead rats, increased in discontinuous low-lead rats, but were unaltered by DMSA treatment. We infer that the elevated blood pressure in the discontinuous low-lead rats is related to an increase in the putative vasoconstrictors, ET-3 and the hypertension-associated protein, without a change in the vasodilator, EDRF. With DMSA treatment, plasma cyclic GMP in low-lead rats increased above normal, and the hypertension associated protein decreased, resulting in lowered blood pressure. DMSA was shown to act as an antioxidant in vitro. Thus the DMSA effect on plasma cGMP (EDRF) may occur via a scavenging effect on EDRF-inactivating reactive oxygen species. (C) 1994 Academic Press, Inc.