Effects of varying impulse number on cotransmitter contributions to sympathetic vasoconstriction in rat tail artery

We examined the contributions of the cotransmitters norepinephrine (NE), ATP, and neuropeptide Y (NPY) to sympathetically evoked vasoconstriction in the rat tail artery in isolated vascular rings by using 1-100 stimulation impulses at 20 Hz. Phentolamine (2 muM), the alpha-adrenoceptor antagonist, markedly reduced responses to all stimuli, although responses to lower impulse numbers were reduced less than responses to longer trains. The purinergic receptor antagonist suramin (100 muM) reduced all responses, but to a much greater extent with few impulse trains. Responses were further reduced or abolished by addition of the second antagonist. Any remaining responses were abolished by the NPY-Y-1 receptor antagonist BIBP-3226 (75 nM). NPY had a direct agonist action and potentiated sympathetically mediated responses. NPY (75 nM) potentiated responses and BIBP-3226 decreased responses to 2- and 20-impulse trains. Both affected responses from 2 impulses to >20 impulses, but there was no preferential effect on purinergic contributions to responses because neurally released NPY potentiated both pure NE and ATP responses equally. We conclude that all three cotransmitters contribute significantly to vascular responses and their contribution varies markedly with impulse numbers. There is considerable synergy between cotransmitters, especially with lower impulse numbers where NPY contributions are greater than expected.