Prejunctional neuropeptide Y (NPY) Y-1 receptors on cardiac sympathetic neu
rons mediate transient inhibition of chronotropic responses in rabbit isola
ted right atria. The function of these receptors remains speculative. We in
vestigated a possible functional role for these receptors in modulation of
the baroreceptor-heart rate (HR) reflex in the conscious rabbit. Mean arter
ial pressure (MAP) responses to a range of doses of the Y-1 receptor agonis
t [Leu(31),Pro(34)]NPY (1-8 mu g/kg, i.v.) were constructed in ganglion-blo
cked 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. GR231
118 shifted the two-point [Leu(31),Pro(34)]NPY dose-presser response relati
on by 10- to 30-fold. A single estimate of the functional half-life of a bo
lus 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 m
u g/kg/h, i.v.). GR231118 caused an initial transient presser response and
bradycardia, followed by a depressor response and a more sustained tachycar
dia. Infusion of GR231118 had no effect on the baroreceptor-HR reflex. Prej
unctional 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.