Vascular nitric oxide: Beyond eNOS

J Pharmacol Sci. 2015 Oct;129(2):83-94. doi: 10.1016/j.jphs.2015.09.002. Epub 2015 Sep 28.


As the first discovered gaseous signaling molecule, nitric oxide (NO) affects a number of cellular processes, including those involving vascular cells. This brief review summarizes the contribution of NO to the regulation of vascular tone and its sources in the blood vessel wall. NO regulates the degree of contraction of vascular smooth muscle cells mainly by stimulating soluble guanylyl cyclase (sGC) to produce cyclic guanosine monophosphate (cGMP), although cGMP-independent signaling [S-nitrosylation of target proteins, activation of sarco/endoplasmic reticulum calcium ATPase (SERCA) or production of cyclic inosine monophosphate (cIMP)] also can be involved. In the blood vessel wall, NO is produced mainly from l-arginine by the enzyme endothelial nitric oxide synthase (eNOS) but it can also be released non-enzymatically from S-nitrosothiols or from nitrate/nitrite. Dysfunction in the production and/or the bioavailability of NO characterizes endothelial dysfunction, which is associated with cardiovascular diseases such as hypertension and atherosclerosis.

Keywords: Endothelial cells; L-arginine; Nitrate/nitrite; Nitric oxide; Nitric oxide synthase; S-nitrosothiols; Vascular smooth muscle.

Publication types

  • Review

MeSH terms

  • Animals
  • Arginine / metabolism
  • Cardiovascular Diseases / etiology
  • Cell Physiological Phenomena
  • Cyclic GMP / metabolism
  • Endothelium, Vascular / physiology
  • Endothelium, Vascular / physiopathology
  • Guanylate Cyclase / metabolism
  • Humans
  • Muscle Contraction
  • Muscle Tonus / physiology
  • Muscle, Smooth, Vascular
  • Nitrates / metabolism
  • Nitric Oxide / biosynthesis
  • Nitric Oxide / physiology*
  • Nitric Oxide Synthase Type III / physiology
  • Nitrites / metabolism
  • S-Nitrosothiols / metabolism
  • Signal Transduction


  • Nitrates
  • Nitrites
  • S-Nitrosothiols
  • Nitric Oxide
  • Arginine
  • Nitric Oxide Synthase Type III
  • Guanylate Cyclase
  • Cyclic GMP