Evidence for an up-regulation of EDHF-mediated relaxation is seen in small resistance arteries and arterioles from animal models of diet-induced obesity [34]–[36], hypercholesterolemia [37], hypertension [38], diabetes [39] and in ApoE and LDL receptor-deficient mice fed a high fat diet in adult life [40]. This evidence concerns the gene APOE and obesity due to melanocortin 4 receptor deficiency.