Serone A P, Wright C E, Angus J A
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
J Cardiovasc Pharmacol. 2000 Feb;35(2):315-21. doi: 10.1097/00005344-200002000-00021.
Prejunctional neuropeptide Y (NPY) Y1 receptors on cardiac sympathetic neurons mediate transient inhibition of chronotropic responses in rabbit isolated right atria. The function of these receptors remains speculative. We investigated a possible functional role for these receptors in modulation of the baroreceptor-heart rate (HR) reflex in the conscious rabbit. Mean arterial pressure (MAP) responses to a range of doses of the Y1 receptor agonist [Leu31,Pro34]NPY (1-8 microg/kg, i.v.) were constructed in ganglion-blocked rabbits. After administration of the selective Y1 receptor antagonist GR231118(150 microg/kg, i.v.), two-point [Leu31,Pro34]NPY dose-pressor responses were assessed. Linear regression analysis of the relation between the shift in the [Leu31,Pro34]NPY dose-pressor response lines against time was used as an estimate of the functional half-life of GR231118. GR231118 shifted the two-point [Leu31,Pro34]NPY dose-pressor response relation by 10- to 30-fold. A single estimate of the functional half-life of a bolus dose of GR231118 was 25 +/- 2 min. This determination allowed a steady-state Y1-receptor blockade to be established by a bolus and infusion. In a separate group of rabbits, the baroreceptor-HR reflex was assessed before and 30 min after administration of GR231118 (150 microg/kg bolus, then 150 microg/ kg/h, i.v.). GR231118 caused an initial transient pressor response and bradycardia, followed by a depressor response and a more sustained tachycardia. Infusion of GR231118 had no effect on the baroreceptor-HR reflex. Prejunctional Y1 receptors appear not to mediate a tonic inhibition of cardiac sympathetic neurotransmission in the conscious rabbit during physiological manipulations in MAP. However, activation of postjunctional Y1 receptors by neuronal or circulating NPY may be important in maintenance of vascular tone in the conscious rabbit.
心脏交感神经元上的节前神经肽Y（NPY）Y1受体介导兔离体右心房变时反应的短暂抑制。这些受体的功能仍属推测。我们研究了这些受体在清醒兔压力感受器-心率（HR）反射调节中的可能功能作用。在神经节阻断的兔中构建了对一系列剂量的Y1受体激动剂[Leu31，Pro34]NPY（1 - 8微克/千克，静脉注射）的平均动脉压（MAP）反应。给予选择性Y1受体拮抗剂GR231118（150微克/千克，静脉注射）后，评估两点[Leu31，Pro34]NPY剂量-升压反应。[Leu31，Pro34]NPY剂量-升压反应线随时间的变化关系的线性回归分析用作GR231118功能半衰期的估计。GR231118使两点[Leu31，Pro34]NPY剂量-升压反应关系改变了10至30倍。一次推注剂量的GR231118的功能半衰期单次估计为25±2分钟。这一测定使得通过推注和输注建立稳态Y1受体阻断成为可能。在另一组兔中，在给予GR231118（150微克/千克推注，然后150微克/千克/小时，静脉注射）前和给药后30分钟评估压力感受器-HR反射。GR231118引起初始短暂的升压反应和心动过缓，随后是降压反应和更持续的心动过速。输注GR231118对压力感受器-HR反射无影响。在清醒兔MAP的生理操作过程中，节前Y1受体似乎不介导对心脏交感神经传递的紧张性抑制。然而，神经元或循环NPY对节后Y1受体的激活在维持清醒兔的血管张力方面可能很重要。
