M. Moriarty et al., PHARMACOLOGICAL SEPARATION OF CARDIO-ACCELERATOR AND VAGAL INHIBITORYCAPACITIES OF SYMPATHETIC-NERVES, Journal of the autonomic nervous system, 43(1), 1993, pp. 7-16
Prolonged attenuation of vagal action at the heart, proposed to be due
to release of the sympathetic cotransmitter neuropeptide Y (NPY), fol
lows stimulation of cardiac sympathetic nerves. It has been shown that
pretreatment with reserpine depletes cardiac and neuronal stores of b
oth noradrenaline and NPY, while combined pretreatment with reserpine
and the ganglion blocking agent chlorisondamine reduces depletion of N
PY, while still depleting noradrenaline. The effects of reserpine pret
reatment and combined chlorisondamine and reserpine pretreatment on th
e inhibition of cardiac vagal action evoked by cardiac sympathetic ner
ve stimulation (16 Hz, 2 min) were compared in anaesthetised dogs. In
dogs with no pretreatment (n = 6), sympathetic stimulation evoked an i
mmediate cardio-acceleration, and a prolonged inhibition of cardiac va
gal action, with a maximum percent inhibition (MPI) and time to half-r
ecovery (T50) of 78 +/- 6% and 16 +/- 2 min respectively. In dogs pret
reated with reserpine (n = 6, 1 mg/kg, 24 h), the immediate cardio-acc
eleration (ANOVA, P < 0.01), and the magnitude (MPI = 31.8%, ANOVA, P
< 0.001) and duration (T50 = 6 +/- 1 min, ANOVA, P < 0.05) of inhibiti
on of cardiac vagal action following sympathetic stimulation were sign
ificantly attenuated. In dogs with combined chlorisondamine (n = 5, 2
mg/kg, 48 and 24 h) and reserpine pretreatment, there was again signif
icantly reduced cardio-acceleration (ANOVA, P < 0.01), but the inhibit
ion of cardiac vagal action following sympathetic stimulation did not
significantly differ from untreated animals (MPI = 79 +/- 8%, T50 = 21
+/- 6 min). Intravenous injections of NPY (25-50 mug/kg) evoked prolo
nged inhibition of cardiac vagal action in untreated and both groups o
f pretreated animals. These experiments indicate that the cardio-accel
erator and vagal inhibitory capacities of sympathetic nerve stimulatio
n can be separated, and are consistent with the sympathetic vagal inhi
bitory factor being NPY.