Neuropeptide Y (NPY) is a central neuromodulator and peripheral sympathetic neurotransmitter that also has important regulatory roles in cardiovascular, neuroendocrine, immune and metabolic functions during stress. Focusing on the peripheral actions of the peptide in rodent models, we summarize recent studies from our laboratory demonstrating that stress-induced release of NPY mediates accelerated atherosclerosis/restenosis, obesity and metabolic-like syndrome, particularly when combined with a high fat, high sugar diet. In this review, we propose mechanisms of NPY's actions, its receptors and cellular substrates that increase the risk for cardiovascular and metabolic diseases when chronic stress is associated with pre-existing vascular injury and/or states of hypernutrition.
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