Boric M P, Martinez A, Donoso M V, Huidobro-Toro J P
Departamento de Ciencias Fisiologicas, Pontificia Universidad Catolica de Chile, Casilla, Santiago, Chile.
Eur J Pharmacol. 1995 Dec 29;294(2-3):391-401. doi: 10.1016/0014-2999(95)00556-0.
The microvascular effects of neuropeptide Y, and two analogs with preferential affinity for different neuropeptide Y receptor subtypes, were assessed by intravital microscopy on the hamster cheek pouch. The interaction of neuropeptide Y and its analogs with noradrenaline was also studied. Superfusion with 0.1-300 nM neuropeptide Y caused a concentration-dependent reduction in microvascular conductance that was paralleled by reductions in arteriolar and venular diameters. These effects of neuropeptide Y were equipotent with noradrenaline, but slower to develop and longer-lasting than that of noradrenaline. Neuropeptide Y did not affect permeability to macromolecules, as measured by extravasation of fluorescent dextran. The neuropeptide Y Y1 receptor agonist, [Leu31,Pro34]neuropeptide Y, mimicked neuropeptide Y with similar potency but shorter duration, while neuropeptide Y-(13-36), a neuropeptide Y Y2 receptor agonist, was at least 10-fold less potent than neuropeptide Y to induce a delayed and prolonged reduction in microvascular conductance. The joint superfusion of 1 nM neuropeptide Y plus 0.1 mu M noradrenaline did not cause synergism, nor even summation of effects, but reduced the contractile effect of noradrenaline. No synergism was observed after a 10 min priming with 1 nM neuropeptide Y, followed by its joint application with 0.1 mu M noradrenaline, but a significant vasodilation and hyperemia ensued upon stopping noradrenaline application. Priming with 1 nM [Leu31,Pro34]neuropeptide Y prolonged noradrenaline vasoconstriction without evidence of hyperemia. In contrast, priming with 1 nM neuropeptide Y-(13-36) significantly antagonized noradrenaline vasoconstriction. These findings indicate that both neuropeptide Y receptor subtypes are present in arterioles and venules of the hamster, and suggest that their activation with neuropeptide Y induces a rapid (Y1 receptor subtype activation) and a delayed (Y2 receptor subtype activation) vasocontractile response. The interaction with noradrenaline is complex, without evidence for synergism, but neuropeptide Y Y2 receptor activation seems to antagonize noradrenaline and/or to facilitate auto-regulatory vasodilation after the catecholamine-induced vasoconstriction.
通过活体显微镜观察仓鼠颊囊，评估了神经肽Y以及对不同神经肽Y受体亚型具有优先亲和力的两种类似物的微血管效应。还研究了神经肽Y及其类似物与去甲肾上腺素的相互作用。用0.1 - 300 nM神经肽Y进行超灌注会导致微血管传导率呈浓度依赖性降低，同时小动脉和小静脉直径也会减小。神经肽Y的这些效应与去甲肾上腺素相当，但起效比去甲肾上腺素慢，持续时间比去甲肾上腺素长。通过荧光葡聚糖外渗测量，神经肽Y不影响对大分子的通透性。神经肽Y Y1受体激动剂[Leu31,Pro34]神经肽Y模拟了神经肽Y的作用，效力相似但持续时间较短，而神经肽Y - (13 - 36)，一种神经肽Y Y2受体激动剂，诱导微血管传导率延迟和延长降低的效力比神经肽Y至少低10倍。1 nM神经肽Y与0.1 μM去甲肾上腺素联合超灌注既不产生协同作用，甚至也没有效应相加，但会降低去甲肾上腺素的收缩效应。在用1 nM神经肽Y预灌注10分钟后，再将其与0.1 μM去甲肾上腺素联合应用，未观察到协同作用，但在停止去甲肾上腺素应用后会出现明显的血管舒张和充血。用1 nM[Leu31,Pro34]神经肽Y预灌注会延长去甲肾上腺素的血管收缩作用，且无充血迹象。相反，用1 nM神经肽Y - (13 - 36)预灌注会显著拮抗去甲肾上腺素的血管收缩作用。这些发现表明，两种神经肽Y受体亚型都存在于仓鼠的小动脉和小静脉中，并表明用神经肽Y激活它们会诱导快速（Y1受体亚型激活）和延迟（Y2受体亚型激活）的血管收缩反应。与去甲肾上腺素的相互作用很复杂，没有协同作用的证据，但神经肽Y Y2受体激活似乎会拮抗去甲肾上腺素和/或促进儿茶酚胺诱导的血管收缩后的自动调节性血管舒张。
