Nitroxyl (HNO): the Cinderella of the nitric oxide story.

Until recently, most of the biological effects of nitric oxide (NO) have been attributed to its uncharged state (NO*), yet NO can also exist in the reduced state as nitroxyl (HNO or NO(-)). Putatively generated from both NO synthase (NOS)-dependent and -independent sources, HNO is rapidly emerging as a novel entity with distinct pharmacology and therapeutic advantages over its redox sibling, NO*. Thus, unlike NO*, HNO can target cardiac sarcoplasmic ryanodine receptors to increase myocardial contractility, can interact directly with thiols and is resistant to both scavenging by superoxide (*O2-) and tolerance development. HNO donors are protective in the setting of heart failure in which NO donors have minimal impact. Here, we discuss the unique pharmacology of HNO versus NO* and highlight the therapeutic potential of HNO donors in the treatment of cardiovascular disease.