has been suggested to be more important in female arteries to confer endothelium-dependent dilatation, while NO played a predominant role in arteries from males. The latter finding indeed concurs with previous reports in several vascular beds, including mesenteric and tail arteries from rats as well as genital arteries from rabbits. These findings together suggest that under pathological conditions EDHF could compensate for the loss of NO in female rather than in male arteries Summary Based on current evidence, the term of endothelium-derived hyperpolarising factor should represent a mechanism rather than a specific factor. The mechanism(s) of endothelium-dependent hyperpolarization (i.e., EDHF-mediated relaxation) seems to be heterogeneous depending on several factors (e.g., size and vascular bed), surrounding environment (oxidative stress, hypercholesterolemia) and demand (compensatory). Different endothelial mediators or pathways involved in EDHF-mediated relaxation may also work simultaneously and/or substitute each other. It implies a reasonable physiological sense, although to some extent and when EDHF acts as backup mechanism for endothelium-dependent relaxation in the present of compromised NO contribution. Thus, alternatives for EDHF-typed responses (H2O2, K+ etc.) will provide a guarantee for compensation of endothelial function. However, once the involvement of a certain endothelium-derived vasodilator for a given vascular bed is confirmed, it is preferred that they be described by their proper name (i.e., endothelium-derived H2O2, or CNP), and no longer be termed as “EDHF”. Although the role of EDHF in the genesis of Cardiovascular Disease remains to be further elucidated, the EDHF contribution and its importance at the level of small arteries delivers a theoretical opportunity to control systemic blood pressure. There is an increasing experimental evidence to suggest that treatment of the EDHF system could provide a means to control blood pressure and blood flow to target organs in compatible way achieved by manipulations of NO system. Since “EDHF story” is particularly heterogeneous and based mainly on animal studies, the most important and demanding current task is to strengthen our knowledge about EDHF action in human arteries in health and disease. See also Endothelium-derived relaxing factor References Biomolecules Vasodilators Angiology