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.
Irvine
Jennifer C
JC
Department of Pharmacology, Monash University, Clayton, VIC, Australia.
Ritchie
Rebecca H
RH
Favaloro
Joanne L
JL
Andrews
Karen L
KL
Widdop
Robert E
RE
Kemp-Harper
Barbara K
BK
D000437:Alcoholism / Q000188:drug therapy; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000188:drug therapy; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology / Q000627:therapeutic use; D009589:Nitrogen Oxides / Q000737:chemistry / Q000378:metabolism*
D000975:Antioxidants; D020030:Nitric Oxide Donors; D009589:Nitrogen Oxides; D009569:Nitric Oxide; C039900:nitroxyl