Browsing by Author "Brown, N"

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    Stimulation of the sympathetic perimesenteric arterial nerves releases neuropeptide Y potentiating the vasomotor activity of noradrenaline: Involvement of neuropeptide Y-Y-1 receptors
    (1997) Donoso, MV; Brown, N; Carrasco, C; Cortes, V; Fournier, A; HuidobroToro, JP
    Neuropeptide Y (NPY) appears to be involved in the sympathetic regulation of vascular tone. To assess the putative role of NPY in mesenteric circulation, the release and biological effect of NPY were examined after electrical stimulation of perimesenteric arterial nerves, Nerve stimulation with trains of 2-30 Hz increased the perfusion pressure of the arterially perfused rat mesenteric bed in a frequency-and time-dependent fashion, Trains of 15-30 Hz significantly displaced to the left, approximately threefold, the noradrenaline (NA)-induced presser concentration-response curve, in addition to increasing significantly its efficacy. Perfusion with 10 nM exogenous NPY mimicked the electrical stimulation effect, causing a threefold leftward shift of the NA concentration-response curve and increasing the maximal NA response. These effects were antagonized by 100 nM BIBP 3226, indicating the activity of NPY-Y-1 receptors. Electrical stimulation of the perimesenteric nerves released immunoreactive NPY (ir-NPY) in a frequency-dependent fashion; the ir-NPY coelutes with synthetic NPY as confirmed by HPLC. Both the electrically induced presser response and the calcium-dependent release of NPY were obliterated in preparations perfused with 1 mu M guanethidine or in rats pretreated intravenously for 48 h with 6-hydroxydopamine, thus revealing the sympathetic origin of these phenomena. Only a small proportion of the total NPY content in the perimesenteric arterial nerves is released after electrical stimulation. Chromatographic studies of the physiological sources of the ir-NPV support that NPY fragments are generated via peptidase degradation. The present findings demonstrate that NPY is re[eased from the perimesenteric arterial sympathetic nerves and acts, via the activation of NPY-Y-1 receptors, as the mediator responsible for the potentiation of NA's effect on perfusion pressure in the isolated rat mesenteric bed.
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    Synergism between neuropeptide Y and norepinephrine highlights sympathetic cotransmission
    (1999) Cortés, V; Donoso, MV; Brown, N; Fanjul, R; López, C; Fournier, A; Huidobro-Toro, JP
    Although abundant literature supports the notion that neuropeptide Y (NPY) synergizes in vivo and in vitro, the vasomotor activity elicited by norepinephrine (NE), the converse interaction (i.e,, the adrenergic modulation of the NPY vasomotor response) has been less characterized. To assess whether NE synergizes the vasomotor effect of NPY, the rat arterial mesenteric bed was chosen as a model experimental system. Mesenteries were precontracted with NE and few minutes later were pelf used with exogenous NPY. Under these conditions, NPY contracted the arterial mesenteric bed with an EC50 value of 0.72 +/- 0.06 nM. NPY was unable to contract this vascular territory without an agonist-induced precontraction, Other agonists, such as endothelin-1, a synthetic analog of prostaglandin F-2 alpha, or 5-hydroxytryptamine, also were effective primers because in their presence, NPY was a potent vasoconstrictor. In contrast, mesenteries precontracted with KCI failed to evidence the NPY-induced rise in perfusion pressure. Two structural analogs of NPY, PW and [Leu(31),Pro(34)]NPY, mimicked the activity of NPY. The NPY fragment 13-36 did not elicit such a response. All NPY analogs exhibited less efficacy and potency relative to NPY. The NPY- and related structural analog-induced vasoconstriction was competitively and reversibly antagonized by BIBP 3226; the pA(2) of the NPY interaction was 7.0. The application of 0.1 to 1 mu M BIBP 3226 or 0.1 to 10 nM prazosin at the peak of the NPY vasomotor response elicited a gradual blockade of the vasoconstriction. Although BIBP 3226 blocked the increase in perfusion pressure elicited by NPY, leaving unaffected the NE-induced tone, 10 nM prazosin blocked the full response, including the NE-induced component. Tissue preincubation with 200 nM nifedipine abolished the NPY-induced vasoconstriction; likewise, the acute application of 10 to 100 nM nifedipine blocked gradually the maximal NPY-induced contraction. Removal of the mesenteric endothelial layer increased the potency of NPY by 2-fold; it also slightly potentiated the antagonist activity of BIBP 3226, The synergism between NPY and NE backs the principle of sympathetic cotransmission.