Modulatory Role of Nitric Oxide on the Vasomotor Actions of NPY in Porcine Cerebral Arteries

Neuropeptide Y (NPY) is a sympathetic co-transmitter that mediates vasoconstriction. However, there is evidence that it may also mediate dilation through a nitric oxide (NO)-dependent mechanism.

Objective

We used a swine model to examine how NPY influences cerebral vascular regulation and hypothesized that NPY would elicit both vasoconstrictor and vasodilatory effects, and that such effects would be modulated partially by NO signaling.

Methods

Briefly, cerebral perfusion and blood pressure were monitored during intracarotid saline or NPY infusion (0.1 μg/kg) in the presence and absence of NO synthase (NOS) inhibition (N^G-nitro-l-arginine methyl ester; 0.35 mg/kg/min). Separately, Y1 receptor distribution (immunohistochemistry) and vasomotor responses to intra- and extraluminal NPY under control and NOS inhibition conditions were examined in isolated arteries.

Results

Intracarotid NPY infusions elicited transient dilation that was blocked by NOS inhibition. In isolated pial arteries, distinct populations of NPY-Y1 receptors were observed on both the vascular smooth muscle (VSM) and endothelium. Extraluminal application of NPY elicited vasoconstriction, while intraluminal delivery elicited vasodilation. NOS inhibition enhanced the magnitude of vasoconstriction in isolated pial arteries. Endothelial denudation, Y1 receptor antagonism, and NOS inhibition each blunted NPY-induced vasodilation.

Conclusion

These data suggest both vasoconstrictor and vasodilatory effects of NPY are modulated partially by NO signaling.