Neuropeptide Y: presence in perivascular noradrenergic neurons and vasoconstrictor effects on skeletal muscle blood vessels in experimental animals and man.

The presence of neuropeptide Y (NPY)-like immunoreactivity (-LI) in sympathetic perivascular nerves and the functional effects of NPY and noradrenaline (NA) on vascular tone were studied in skeletal muscle of various species. A dense network of NPY-LI was found around arteries and arterioles but not venules in the gluteus maximus muscle of man, gracilis muscle of dog, tenuissimus muscle of rabbit and quadriceps muscle of cat, rat, guinea pig and pig. The distribution of NPY-immunoreactive (-IR) nerves was closely correlated to the presence of tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH)-positive fibers, two markers for noradrenergic neurons. Double-staining experiments revealed that NPY- and TH-IR as well as NPY- and DBH-IR nerve fibers around arteries and arterioles were identical. The veins and venules, however, lacked or had a very sparse innervation of NPY-, TH- and DBH-positive fibers. The NPY- and TH-IR nerves in quadriceps muscle of the guinea pig were absent after treatment with 6-hydroxydopamine. Lumbosacral sympathetic ganglia from the same species contained many NPY-positive cells which were also TH- and DBH-IR. NPY-LI was also detected by radioimmunoassay in extracts of skeletal muscle from guinea pig, rabbit, dog, pig and man as well as of lumbosacral sympathetic ganglia. The content of NPY-LI in skeletal muscle was relatively low (0.1-0.4 pmol/g), whereas lumbosacral sympathetic ganglia had a much higher content (48-88 pmol/g). NPY (10(-7) M) contracted arterioles in the tenuissimus muscle of the rabbit to a similar extent (by 65%) as NA (10(-6) M), as studied by intravital microscopy in vivo. NPY had no effect on the corresponding venules while NA caused a slight contraction of these vessels. In vitro studies of small human skeletal muscle arteries and veins revealed that NPY was more potent than NA in contracting the arteries, and the highest concentration of NPY (5 x 10(-7) M) caused a contraction of a similar magnitude as NA 10(-5) M. NA contracted veins from human skeletal muscle, while NPY had only small effects. It is suggested that NPY, together with NA, could be of importance for sympathetic control of skeletal muscle blood flow.