Neuropeptide Y potentiates noradrenaline-evoked vasoconstriction: mode of action.
Neuropeptide Y (NPY), which co-exists with noradrenaline (NA) in postganglionic sympathetic nerves, was able to potentiate NA-evoked constriction in certain isolated rabbit blood vessels. The phenomenon was observed in the femoral, the gastroepiploic and the pulmonary arteries but not in the femoral or the gastroepiploic veins or in the aorta. Thus, NPY potentiated NA-evoked vasoconstriction predominantly in muscular arteries with alpha-1 adrenoceptors. NPY-related peptides, such as peptide YY and to some extent pancreatic polypeptide shared this ability, whereas calcitonin gene-related peptide or LPLRFamide did not. The mode of action by which NPY potentiates NA-evoked vasoconstriction was analyzed using the femoral artery. Pretreatment of the vessel with cocaine, a blocker of amine re-uptake, or rolipram, an inhibitor of phosphodiesterase, left the potentiation unaffected, whereas Na+ deficiency or ouabain, an inhibitor of Na+/K+-adenosine triphosphatase, abolished this effect of NPY. Nifedipine, a blocker of Ca++ entry, or removal of extracellular Ca++ shortly before the application of NPY had little effect. After prolonged exposure to a Ca++-free medium (with ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid) the maximum response to NA was greatly reduced and the potentiating effect of NPY was abolished. Thus, the potentiation of NA-evoked vasoconstriction by NPY seems to depend upon the presence of Na+ but not upon a Ca++ influx. An intracellular sequestered Ca++ pool appears to play a critical role.
D000818:Animals; D004357:Drug Synergism; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009478:Neuropeptide Y; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D010042:Ouabain / Q000494:pharmacology; D019894:Peptide YY; D010455:Peptides / Q000494:pharmacology; D011817:Rabbits; D012964:Sodium / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*
D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D010455:Peptides; D019894:Peptide YY; D004533:Egtazic Acid; D010042:Ouabain; D012964:Sodium; D009543:Nifedipine; D009638:Norepinephrine