However, it is also possible for excessive release of NO to induce tissue injury in a cGMP-independent manner: –NO may also combine with O2−, leading to the formation of peroxynitrite anion—which under conditions of rapid formation may induce nitrosative stress via the nitrosation of protein tyrosine residues—and activation of the “energy sink”/DNA reparative enzyme poly-(ADP/ribose) polymerase-1 (PARP-1)—which is implicated in the impairment of myocardial contractility and the potential induction of heart failure [10,11]. The gene discussed is PARP1; the disease is heart failure.