In order to rule out the possible contribution of additional factors in the adipose-mediated potentiation of contraction, experiments were performed to assess other vasoconstrictor pathways and targets known to play a role in vascular disease development and obesity, such as endothelin-1 [43] and reactive oxygen species [22], [25], [44]. This evidence concerns the gene EDN1 and obesity due to melanocortin 4 receptor deficiency.