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Nicotianamine (NA) is a nonprotein amino acid that inhibits the angiotensin I-converting enzyme (ACE) in the renin-angiotensin system (RAS). The purpose of this study is to prove that NA contributes to the suppression of hypertension by preferential inhibition of ACE. On comparison with EDTA-a chelator-we found that the inhibition pattern of NA for ACE is that of mixed inhibition and that NA exhibits weak chelation effects for zinc, copper, and cobalt ions. Therefore, we investigated whether NA inhibited zinc-containing enzymes other than ACE in vitro. The results revealed that NA does not inhibit leucine aminopeptidase or alkaline phosphatase in rat serum. On the other hand, NA demonstrated specific inhibitory effects for rat serum ACE and aortic ACE. These results suggest that the preferential inhibition of circulatory and tissue ACE by NA can contribute to the suppression of hypertension.