Hypoxic Remodeling of Fetal Cerebral Arteries Involves The NPY/Y1 Pathway

Abstract

The sympathetic perivascular innervation has long been suggested to exert trophic influences on cerebral arteries, particularly during hypoxic adaptation. Although most of this effect has been attributed to the actions of norepinephrine, sympathetic nerves also co‐release NPY together with norepinephrine. This study tests the hypothesis that NPY released from sympathetic nerves also contributes to hypoxic remodeling of fetal lamb cerebral arteries. Hypoxic acclimatization for 110 days increased NPY levels by 230% in nerve intact arteries. Whereas sympathectomy (SANX) had no significant effect in normoxic arteries, it decreased NPY levels in hypoxic arteries (25%). Hypoxia also increased Y1 receptor levels (70%) but only in nerve intact arteries. SANX decreased Y1 levels (30%) in hypoxic arteries. Confocal microscopy revealed that organ culture with 100 nM NPY potently decreased the colocalization of Non‐Muscle Myosin with Smooth Muscle Alpha‐Actin, indicating increased contractile differentiation. In nerve intact arteries, NPY decreased myogenic tone whereas in SANX arteries NPY increased myogenic tone. Co‐culture with the Y1 antagonist BIBP‐3226 (5 µM) reversed these effects of NPY. Taken together, these results suggest that NPY released from sympathetic nerves contributes to remodeling of the fetal cerebral vasculature during hypoxic acclimatization.