Selective constriction of small cutaneous arteries by NPY matches distribution of NPY in sympathetic axons

Abstract

This study has begun to investigate some functional implications of the differential localization of neuropeptide Y (NPY) in sympathetic neurons supplying different arterial segments in the cutaneous circulation of the guinea-pig ear. Responses of the main ear artery to exogenous NPY and norepinephrine (NE) were examined in vitro by measuring isometric tension. Responses of smaller arterial vessels to application of exogenous NPY or NE to the adventitial surface were examined in anaesthetized, ventilated guinea-pigs, by measuring changes in internal vessel diameter using video microscopy. Some arterial segments subsequently were examined for the presence of immunoreactivity (IR) to tyrosine hydroxylase (TH) and NPY. NPY (1 nM-10 microM) contracted the main ear artery (EC50 = 10 nM; max. contraction = 30% KCl), and 1 nM NPY produced slight potentiation of contractions produced by NE. In vivo, local applications of NPY (1-10 microM) constricted only a subpopulation of arterial vessels (23 of 41). All vessels constricted by NPY were innervated by axons containing IR to both TH and NPY, and as a population, were more proximal in the arterial tree (branch orders 3 to 6) than were vessels insensitive to NPY (branch orders 4 to 8). Most vessels insensitive to NPY were arterioles and arterio-venous anastomoses < 40 microns in diameter, which were innervated by axons containing TH-IR but not NPY-IR. In contrast, local application of NE (1-30 microM) constricted all vessels examined in vivo. When present, NPY constrictions had a longer latency (15-45 s) and duration (3-4 min) than NE constrictions of the same vessel segments. In vivo, NPY sometimes potentiated the peak amplitude of NE constrictions (2 of 7 vessels), but only in vessels where NPY also produced direct constriction. These results reveal an excellent correlation between the localization of NPY in sympathetic axons, and the location of postsynaptic NPY receptors throughout the cutaneous arterial system. Any NPY released in response to strong activation of cutaneous sympathetic neurons is likely to act preferentially on the proximal cutaneous arteries, and to lead to a more prolonged constriction of these arteries than of more distal arterioles and arterio-venous anastomoses.