Diverse functions of endothelial NO synthases system: NO and EDH

Hiroaki Shimokawa, Shigeo Godo

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)


Endothelium-dependent relaxations are predominantly regulated by nitric oxide (NO) in large conduit arteries and by endothelium-dependent hyperpolarization (EDH) in small resistance vessels. Although the nature of EDH factors varies depending on species and vascular beds, we have previously demonstrated that endothelial NO synthases (eNOS)-derived hydrogen peroxide (H2O2) is an EDH factor in animals and humans. This vessel size-dependent contribution of NO and EDH is, at least in part, attributable to the diverse roles of endothelial NOSs system; in large conduit arteries, eNOS mainly serves as a NO-generating system to elicit soluble guanylate cyclase-cyclic guanosine monophosphate-mediated relaxations, whereas in small resistance vessels, it serves as a superoxide-generating system to cause EDH/H2O2-mediated relaxations. Endothelial caveolin-1 may play an important role for the diverse roles of NOSs. Although reactive oxygen species are generally regarded harmful, the physiological roles of H2O2 have attracted much attention as accumulating evidence has shown that endothelium-derived H2O2 contributes to cardiovascular homeostasis. The diverse functions of endothelial NOSs system with NO and EDH/H2O2 could account for a compensatory mechanism in the setting of endothelial dysfunction. In this review, we will briefly summarize the current knowledge on the diverse functions of endothelial NOSs system: NO and EDH/H2O2.

Original languageEnglish
Pages (from-to)361-366
Number of pages6
JournalJournal of cardiovascular pharmacology
Issue number5
Publication statusPublished - 2016 May 1


  • endothelium-dependent hyperpolarization
  • endothelium-derived relaxing factor
  • hydrogen peroxide
  • nitric oxide
  • nitric oxide synthase

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine


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