TY - JOUR
T1 - Nitric oxide and endothelium-dependent hyperpolarization mediated by hydrogen peroxide in health and disease
AU - Shimokawa, Hiroaki
AU - Godo, Shigeo
N1 - Funding Information:
This work was supported in part by the Grants‐in‐Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Tokyo, Japan, and the Grants‐in‐Aid for Scientific Research from the Ministry of Health, Labour, and Welfare, Tokyo, Japan. The authors are deeply grateful to the late Professor Paul M. Vanhoutte for his lifelong support of our work.
Publisher Copyright:
© 2019 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society)
PY - 2020/8/1
Y1 - 2020/8/1
N2 - The endothelium plays crucial roles in modulating vascular tone by synthesizing and releasing endothelium-derived relaxing factors (EDRFs), including vasodilator prostaglandins, nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) factors. Thus, endothelial dysfunction is the hallmark of atherosclerotic cardiovascular diseases. Importantly, the contribution of EDRFs to endothelium-dependent vasodilatation varies in a distinct vessel size-dependent manner; NO mainly mediates vasodilatation of relatively large, conduit vessels (eg epicardial coronary arteries), while EDH factors in small resistance vessels (eg coronary microvessels). Endothelium-derived hydrogen peroxide (H2O2) is a physiological signalling molecule serving as one of the major EDH factors especially in microcirculations and has gained increasing attention in view of its emerging relevance for cardiovascular diseases. In the clinical settings, therapeutic approaches targeting NO (eg NO donors) or non-specific elimination of reactive oxygen species (eg antioxidant supplements) are disappointingly ineffective for the treatment of various cardiovascular diseases, in which endothelial dysfunction and coronary microvascular dysfunction are substantially involved. These lines of evidence indicate the potential importance of the physiological balance between NO and H2O2/EDH factor. Further characterization and better understanding of endothelium-dependent vasodilatations are important to develop novel therapeutic strategies in cardiovascular medicine. In this MiniReview, we will briefly summarize the current knowledge on the emerging regulatory roles of endothelium-dependent vasodilatations in the cardiovascular system, with a special reference to the two major EDRFs, NO and H2O2/EDH factor, in health and disease.
AB - The endothelium plays crucial roles in modulating vascular tone by synthesizing and releasing endothelium-derived relaxing factors (EDRFs), including vasodilator prostaglandins, nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) factors. Thus, endothelial dysfunction is the hallmark of atherosclerotic cardiovascular diseases. Importantly, the contribution of EDRFs to endothelium-dependent vasodilatation varies in a distinct vessel size-dependent manner; NO mainly mediates vasodilatation of relatively large, conduit vessels (eg epicardial coronary arteries), while EDH factors in small resistance vessels (eg coronary microvessels). Endothelium-derived hydrogen peroxide (H2O2) is a physiological signalling molecule serving as one of the major EDH factors especially in microcirculations and has gained increasing attention in view of its emerging relevance for cardiovascular diseases. In the clinical settings, therapeutic approaches targeting NO (eg NO donors) or non-specific elimination of reactive oxygen species (eg antioxidant supplements) are disappointingly ineffective for the treatment of various cardiovascular diseases, in which endothelial dysfunction and coronary microvascular dysfunction are substantially involved. These lines of evidence indicate the potential importance of the physiological balance between NO and H2O2/EDH factor. Further characterization and better understanding of endothelium-dependent vasodilatations are important to develop novel therapeutic strategies in cardiovascular medicine. In this MiniReview, we will briefly summarize the current knowledge on the emerging regulatory roles of endothelium-dependent vasodilatations in the cardiovascular system, with a special reference to the two major EDRFs, NO and H2O2/EDH factor, in health and disease.
KW - endothelial function
KW - endothelium
KW - endothelium-dependent hyperpolarization
KW - hydrogen peroxide
KW - nitric oxide
KW - nitric oxide synthase
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U2 - 10.1111/bcpt.13377
DO - 10.1111/bcpt.13377
M3 - Review article
C2 - 31846200
AN - SCOPUS:85077869906
VL - 127
SP - 92
EP - 101
JO - Basic and Clinical Pharmacology and Toxicology
JF - Basic and Clinical Pharmacology and Toxicology
SN - 1742-7835
IS - 2
ER -