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Thus, endothelial dysfunction is the hallmark of atherosclerotic cardiovascular diseases. Importantly, the contribution of EDRFs to endothelium\u2010dependent vasodilatation varies in a distinct vessel size\u2010dependent 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\u2010derived hydrogen peroxide (H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>) 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\u2010specific 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 H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\/EDH factor. Further characterization and better understanding of endothelium\u2010dependent 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\u2010dependent vasodilatations in the cardiovascular system, with a special reference to the two major EDRFs, NO and H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\/EDH factor, in health and disease.<\/jats:p>","DOI":"10.1111\/bcpt.13377","type":"journal-article","created":{"date-parts":[[2019,12,17]],"date-time":"2019-12-17T14:35:15Z","timestamp":1576593315000},"page":"92-101","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Nitric oxide and endothelium\u2010dependent hyperpolarization mediated by hydrogen peroxide in health and disease"],"prefix":"10.1111","volume":"127","author":[{"given":"Hiroaki","family":"Shimokawa","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine Tohoku University Graduate School of Medicine Sendai 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