Neuropeptide Y preferentially potentiates responses to adrenergic nerve stimulation by increasing rate of contraction.

Neuropeptide Y (NPY) is colocalized with norepinephrine and coreleased from adrenergic nerves. NPY reportedly can influence vascular neuroeffector transmission in both negative and positive directions. Mechanisms by which NPY effects are exerted and their relative contribution may vary between different blood vessels. Therefore, we investigated effects of NPY on adrenergic neurotransmission in ring segments of the rat tail artery by measuring isometric force development and [3H]norepinephrine release. NPY (1-100 nM) potentiated responses to transmural nerve stimulation (3 Hz, six pulses) by more than 300% but produced no direct contractile effects. NPY potentiated responses to longer transmural nerve stimulation trains (30-100 pulses) or to exogenous norepinephrine by only 30%. NPY had no effect on [3H]norepinephrine overflow with either short (six pulses) or long (30 pulses) stimulation trains. Contractile responses to transmural nerve stimulation were completely blocked by prazosin (10(-7) M) both in the absence and presence of NPY. Since the impact of an increased rate of contraction on the contractile response achieved would be greater with short stimulation trains, the effect of NPY on contraction rate was analyzed. NPY increased the rate of contraction to both norepinephrine and transmural nerve stimulation. It is hypothesized that NPY increases the early (phasic) component of the contractile response by preferentially influencing release of intracellular calcium stores. These findings suggest that the effects of NPY will be more profound on phasic rather than sustained patterns of nerve traffic.