Circulating AM levels increase during intense exercise. They also increase in a number of pathologic states, including essential and pulmonary hypertension, acute myocardial infarction, and cardiac and renal failure. Plasma AM levels are increased in proportion to the severity of these diseases and this can be a useful prognostic marker. The roles of AM in these states remain to be defined, but it is currently thought that the peptide functions as a physiologic antagonist of the actions of vasoconstrictors including ET-1 and ANG II. By virtue of these actions, AM may protect against cardiovascular overload and injury, and AM may be beneficial in the treatment of some cardiovascular diseases.
The neuropeptide Y family is a multiligand/multireceptor system consisting of three polypeptide agonists that bind and activate four distinct receptors with different affinity and potency. The peptides are pancreatic polypeptide (PP), peptide YY (PYY), and neuropeptide Y (NPY). Each peptide consists of 36 amino acids and has an amidated C-terminus. PP is secreted by the islets of Langerhans after food ingestion in proportion to the caloric content and appears to act mainly in the brainstem and vagus to promote appetite suppression, inhibit gastric emptying, and increase energy expenditure; it also exerts direct actions in the gut. PYY is released by entero-endocrine L cells of the distal gut in proportion to food intake and produces anorexigenic effects.
NPY is one of the most abundant neuropeptides in both the central and peripheral nervous systems. Whereas PYY and PP act as neuroendocrine hormones, NPY acts as a neurotransmitter. In the sympathetic nervous system, NPY is frequently localized in noradrenergic neurons and apparently functions both as a vasoconstrictor and as a cotransmitter with norepinephrine. The remainder of this section focuses on NPY.
NPY produces a variety of central nervous system effects, including increased feeding (it is one of the most potent orexigenic molecules in the brain), hypotension, hypothermia, respiratory depression, and activation of the hypothalamic-pituitary-adrenal axis. Other effects include vasoconstriction of cerebral blood vessels, positive chronotropic and inotropic actions on the heart, and hypertension. The peptide is a potent renal vasoconstrictor and suppresses renin secretion, but can cause diuresis and natriuresis. Prejunctional neuronal actions include inhibition of transmitter release from sympathetic and parasympathetic nerves. Vascular actions include direct vasoconstriction, potentiation of the action of vasoconstrictors, and inhibition of the action of vasodilators. NPY promotes angiogenesis and cardiomyocyte remodeling.
The diverse effects of NPY (and PP and PYY) are mediated by four subtypes of NPY receptors designated Y1, Y2, Y4, and Y5. All are Gi protein-coupled receptors linked to mobilization of Ca2+ and inhibition of adenylyl cyclase. Y1 and Y2 receptors are of major importance in the cardiovascular and other peripheral effects of the peptide. Y4 receptors have a high affinity for pancreatic polypeptide and may be a receptor for the pancreatic peptide rather than for NPY. Y5 receptors are found mainly in the central nervous system and may be involved in the control of food intake. They also mediate the activation of the hypothalamic-pituitary-adrenal axis by NPY.