HNO/Thiol Biology as a Therapeutic Target

Nitroxyl (HNO) is a protonated, one-electron reduction product of nitric oxide (NO) with distinct biological effects. Like NO, HNO exerts vasodilatory effects and inhibits platelet aggregation but unlike NO, it stimulates the release of the strongest known vasodilator, calcitonin gene-related peptide and, more importantly, it reacts with thiols to eventually lead to their oxidation to disulfides. It became clearer in recent years that it is this particular chemical property that holds the key to the great pharmacological potential of the HNO donors; the treatment of the heart failure being the best example. The emergence of hydrogen sulfide (H2S), a new gaseous signaling molecule with physiological and pharmacological effects overlapping with those of NO (and HNO), led to some interesting discoveries suggesting the important role of the NO/H2S crosstalk in the endogenous generation of HNO, but also opening up some new perspective for the use of this chemistry as pharmacological substitute for the HNO donors. This book chapter summarizes all recent advancements in the field of HNO (bio)chemistry and pharmacology.