Figure 10

Role of PARP activation in the AII-induced endothelial dysfunction in vivo. ACE produces AII from its precursor, angiotensin I (AI). AII, via its AI AII receptor on the surface of the endothelial cell, activates endothelial cell NADPH oxidase, which produces superoxide \(O_2^{-}\). Superoxide reacts with nitric oxide, produced from the constitutive endothelial NOS, to form peroxynitrite (ONOO). DNA single-strand breaks initiated by ONOO trigger the activation of poly(ADP-ribose) polymerase-1 (PARP), and the resulting intracellular futile metabolic cycle leads to the development of a reversible endothelial dysfunction.