Reactive oxygen species in cardiovascular health and disease: Special references to nitric oxide, hydrogen peroxide, and Rho-kinase

Hiroaki Shimokawa

Research output: Contribution to journalReview articlepeer-review

14 Citations (Scopus)


The interaction between endothelial cells and vascular smooth muscle cells (VSMC) plays an important role in regulating cardiovascular homeostasis. Endothelial cells synthesize and release endothelium-derived relaxing factors (EDRFs), including vasodilator prostaglandins, nitric oxide (NO), and endothelium-dependent hyperpolarization (EDH) factors. Importantly, the contribution of EDRFs to endothelium-dependent vasodilatation markedly varies in a vessel size-dependent manner; NO mainly mediates vasodilatation of relatively large vessels, while EDH factors in small resistance vessels. We have previously identified that endothelium-derived hydrogen peroxide (H2O2) is an EDH factor especially in microcirculation. Several lines of evidence indicate the importance of the physiological balance between NO and H2O2/EDH factor. Rho-kinase was identified as the effectors of the small GTP-binding protein, RhoA. Both endothelial NO production and NO-mediated signaling in VSMC are targets and effectors of the RhoA/Rho-kinase pathway. In endothelial cells, the RhoA/Rho-kinase pathway negatively regulates NO production. On the contrary, the pathway enhances VSMC contraction with resultant occurrence of coronary artery spasm and promotes the development of oxidative stress and vascular remodeling. In this review, I will briefly summarize the current knowledge on the regulatory roles of endothelium-derived relaxing factors, with special references to NO and H2O2/ EDH factor, in relation to Rho-kinase, in cardiovascular health and disease.

Original languageEnglish
Pages (from-to)83-91
Number of pages9
JournalJournal of Clinical Biochemistry and Nutrition
Issue number2
Publication statusPublished - 2020


  • Endothelium
  • Endothelium-derived relaxing factors
  • Hydrogen peroxide
  • Nitric oxide
  • Rho-kinase

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics
  • Clinical Biochemistry


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