Role of NPYY1 receptors in cardiovascular control in the conscious rabbit

Prejunctional neuropeptide Y (NPY) Y-1 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 Y-1 receptor agonist [Leu(31),Pro(34)]NPY (1-8 mu g/kg, i.v.) were constructed in ganglion-blocked rabbits. After administration of the selective Y-1 receptor antagonist GR231118 (150 mu g/kg, i.v.), two-point [Leu(31),Pro(34)]NPY dose-pressor responses were assessed. Linear regression analysis of the relation between the shift in the [Leu(31),Pro(34)]NPY dose-presser response lines against time was used as an estimate of the functional half-life of GR231118. GR231118 shifted the two-point [Leu(31),Pro(34)]NPY dose-presser 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 Y-1-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 mu Lg/kg bolus, then 150 mu g/kg/h, i.v.). GR231118 caused an initial transient presser 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 Y-1 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 Y-1 receptors by neuronal or circulating NPY may be important in maintenance of vascular tone in the conscious rabbit.