LEP and obesity due to melanocortin 4 receptor deficiency: The results of this study confirm our previous findings [17], [18] that: (1) chronic hyperleptinemia either induced in lean rats by administration of exogenous leptin or resulting from diet-induced obesity impairs acute NO-mediated vasodilating effect of leptin, (2) EDHF-dependent effect of leptin is up-regulated under these circumstances and compensates for NO deficiency.