1229u91 and Tachycardia

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.

Topics: Animals; Blood Pressure; Bradycardia; Dose-Response Relationship, Drug; Female; Heart Rate; Male; Neuropeptide Y; Peptides, Cyclic; Pressoreceptors; Rabbits; Receptors, Neuropeptide Y; Tachycardia; Time Factors