Abstract
Background. The chelating agent, ethylenediamine tetraacetic acid (EDTA) is used to treat atherosclerosis. However, it is known to lead to intoxication at doses of more than5g/infusion (1000 mL), and to cause fatal renal toxicity. In vitro studies, the concentration of EDTA used to chelate Ca2+ is usually less than 1 mM. Some scholars have used more than 20 mM EDTA to test for increased Ca2+-chelating activity, but have not discussed the effect of high concentrations of EDTA on smooth muscles or its influence upon other ions. In this study, we attempted to investigate whether EDTA (5mM)-induced vasoconstriction is related to exogenous or endogenous nitric oxide (NO). Methods. This experiment was based on Furchgott's treatment of rabbit aortic smooth muscles. Strips of aorta were carefully tightened with silk threads, and placed in 10 ml of Kreb's Ringer solution with air containing 95% of O2 and5% of CO2. The temperature was kept at 37±5℃ in the organ bath and the pH at 7.3-7.4. The tension was gradually adjusted to 2.0 g. A 90-120 min waiting period was allowed for the apparatus to reach stability before testing. Results. EDTA evoked vasoconstriction when the concentration was higher than 4 mM. The exogenous NO donor, sodium nitroprusside (SNP) markedly inhibited EDTA (5mM)-induced vasoconstriction. The inhibition rate of SNP on EDTA-induced vasoconstriction was 113.7% when the endothelium was absent and 84.4% when present. L-arginine (NO precursor; 1 X 10-4 M) and the inhibitor of NO synthase, Nω-nitro-L-arginine methyl ester (1 X 10-5M), had little effect. However, the cGMP analog, 8-bromoguanosine 3', 5’-cyclic monophosphate (l x 10-5M), inhibited EDTA-induced vasoconstriction. Conclusions. When the concentration was greater than 4 mM, EDTA induced vasoconstriction, reaching its peak effect at a concentration of 60 mM in isolated rabbit aorta. Furthermore, the vasoconstriction induced by5mM EDTA was not directly related to the inhibition of endogenous NO.
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