We have recently demonstrated, using eNOS+/− mice, that heterozygous eNOS deficiency in combination with 30 wks of a high fat diet (a time point not normally associated with endothelial dysfunction in wildtype eNOS+/+ mice) is associated with marked impairment of endothelial function in the carotid artery14,25. Here, NOS3 is linked to endothelial dysfunction.