NOS3 and obesity due to melanocortin 4 receptor deficiency: We previously showed that obesity leads to resistance to both IGF-1 and insulin-mediated activation of eNOS and relaxation of the aorta.2 Studies in humans have shown that IGF-1 increases forearm blood flow consistent with an effect on resistance vessels.24 McCallum et al.25 showed that IGF-1-mediated vasodilatation of aorta is blunted in hypertensive rats and Hasdai et al.26 showed that arteriolar vasorelaxation to IGF-1 is attenuated in experimental hypercholesterolaemia.