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.
Khalil-Manesh
F
F
Department of Medicine, Trace Element Laboratory, Cedars-Sinai Medical Center, Los Angeles, California 90048.
Gonick
H C
HC
Weiler
E W
EW
Prins
B
B
Weber
M A
MA
Purdy
R
R
Ren
Q
Q
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D015913:Chelation Therapy; D006152:Cyclic GMP / Q000097:blood; D016232:Endothelins / Q000097:blood; D007854:Lead; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D004113:Succimer / Q000494:pharmacology* / Q000627:therapeutic use
D016232:Endothelins; D007854:Lead; D004113:Succimer; D006152:Cyclic GMP