Superoxide regulation of endothelin-converting enzyme

Reactive oxygen species (ROS) act as signaling molecules in the cardiovascu lar system, regulating cellular proliferation and migration. However, an ex cess of ROS can damage cells and alter endothelial cell function. We hypoth esized that endogenous mechanisms protect the vasculature from excess level s of ROS. We now shaw that superoxide can inhibit endothelin-converting enz yme activity (ECE) and decrease endothelin-l synthesis. Superoxide inhibits ECE but hydrogen peroxide and nitric oxide do not. Superoxide inhibits ECE by ejecting zinc from the enzyme, and the addition of exogenous zinc resto res enzymatic activity. Superoxide may inhibit other zinc metalloproteinase s by a similar mechanism and may thus play an important role in regulating the biology of blood vessels.