Nitric Oxide

Nitric Oxide

1. Definition, discovery & overview

• Nitric oxide (NO) is an oxide of nitrogen (molecular formula NO) that exists as a free radical with one unpaired electron; it is the smallest endogenous signal molecule and the only one that is a gas at normal body temperature (KDT 8e Ch.37, p.540).
• NO is a gasotransmitter — a labile, freely diffusible gaseous mediator that is synthesised on demand (not stored), acts over very short distances, and is not released by exocytosis (KDT 8e Ch.37, pp.540, 542).
• Since its 1980 identification as a biological mediator, NO is now recognised as a key messenger in the cardiovascular and nervous systems, and in inflammatory and other cell types (KDT 8e Ch.37, p.540).
• Discovery / Nobel trail (KDT 8e Ch.37, p.540):
  • Furchgott & Zawadzki (1980) — acetylcholine relaxed vascular smooth muscle only when the endothelial lining was intact; if the endothelium was rubbed off (denuded), relaxation was lost. They proposed that activated endothelium releases a soluble endothelium-derived relaxing factor (EDRF) that diffuses to the underlying smooth muscle to cause relaxation.
  • Furchgott is credited with the EDRF concept; soon other vasorelaxants (histamine, 5-HT, bradykinin) were shown to act through EDRF release.
  • Ferid Murad (1977) had earlier shown that glyceryl trinitrate (GTN) causes vasodilatation by releasing NO.
  • Louis Ignarro (1987) confirmed that EDRF was in fact NO.
  • Furchgott, Murad and Ignarro shared the 1998 Nobel Prize in Physiology or Medicine for these discoveries (KDT 8e Ch.37, p.540).
• The term EDRF is now understood to be NO (with some contribution from related nitroso species); NO is therefore the molecular identity of the classic endothelium-dependent relaxation pathway (KDT 8e Ch.37, p.540).