Neuropeptide Y Y1 receptors in vascular pharmacology

The existence of neurogenic mediator candidates apart from noradrenaline and acetylcholine involved in the control of vascular tone has attracted enormous attention during the past few decades. One such mediator is neuropeptide Y (NPY), which is co-localized with noradrenaline in sympathetic perivascular nerves. Stimulation of sympathetic nerves in vitro and in vivo causes non-adrenergic vasoconstriction which can be blocked by experimental manipulations that inhibit NPY mechanisms. Thus, the vasopressor response to stimulation of sympathetic nerves can be attenuated by chemical or surgical sympathectomy, treatment with reserpine or other pharmacological agents, and tachyphylaxis to NPY or by NPY antagonists. The NPY field was long plagued by a lack of specific antagonists, but with the recently developed, selective, non-peptide and stable NPY antagonists it has now become possible to study subtypes of this receptor family. For instance, it has become clear that the NPY Y1 receptor mediates most of the direct peripheral effects of NPY on vascular tone. These antagonists promise to stimulate NPY research and will likely unravel the true significance of NPY in cardiovascular control under physiological conditions as well as in pathophysiological states.