STIMULATION OF THE SYMPATHETIC PERIMESENTERIC ARTERIAL NERVES RELEASES NEUROPEPTIDE-Y POTENTIATING THE VASOMOTOR ACTIVITY OF NORADRENALINE - INVOLVEMENT OF NEUROPEPTIDE Y-Y-1 RECEPTORS

Neuropeptide Y (NPY) appears to be involved in the sympathetic regulat ion of vascular tone. To assess the putative role of NPY in mesenteric circulation, the release and biological effect of NPY were examined a fter electrical stimulation of perimesenteric arterial nerves, Nerve s timulation with trains of 2-30 Hz increased the perfusion pressure of the arterially perfused rat mesenteric bed in a frequency-and time-dep endent fashion, Trains of 15-30 Hz significantly displaced to the left , approximately threefold, the noradrenaline (NA)-induced presser conc entration-response curve, in addition to increasing significantly its efficacy. Perfusion with 10 nM exogenous NPY mimicked the electrical s timulation effect, causing a threefold leftward shift of the NA concen tration-response curve and increasing the maximal NA response. These e ffects were antagonized by 100 nM BIBP 3226, indicating the activity o f NPY-Y-1 receptors. Electrical stimulation of the perimesenteric nerv es released immunoreactive NPY (ir-NPY) in a frequency-dependent fashi on; the ir-NPY coelutes with synthetic NPY as confirmed by HPLC. Both the electrically induced presser response and the calcium-dependent re lease of NPY were obliterated in preparations perfused with 1 mu M gua nethidine or in rats pretreated intravenously for 48 h with 6-hydroxyd opamine, thus revealing the sympathetic origin of these phenomena. Onl y a small proportion of the total NPY content in the perimesenteric ar terial nerves is released after electrical stimulation. Chromatographi c studies of the physiological sources of the ir-NPV support that NPY fragments are generated via peptidase degradation. The present finding s demonstrate that NPY is re[eased from the perimesenteric arterial sy mpathetic nerves and acts, via the activation of NPY-Y-1 receptors, as the mediator responsible for the potentiation of NA's effect on perfu sion pressure in the isolated rat mesenteric bed.