Recently, EDHF has been implicated in gender-related differences in blood pressure control. The generation of animals that lack both endothelial nitric oxide synthase (eNOS) and COX-1 (Cyclooxygenase-1, a protein that acts as an enzyme to speed up the production of certain chemical messengers), has allowed a direct assessment of the involvement of EDHF to endothelium-dependent relaxation in small arteries. In mice lacking both eNOS and COX-1, EDHF-mediated response appeared to compensate the absence of endothelial NO in females but not in males. In female mice, the deletion of eNOS and COX-1 did not affect mean arterial blood pressure, while males become hypertensive
In accordance with this study, EDHF 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