Mitogenic effect of neuropeptide Y in rat vascular smooth muscle cells.
Neuropeptide Y (NPY) is a vasoconstrictor released with norepinephrine from perivascular sympathetic nerves. Since sympathetic nerves appear to play a role in vascular smooth muscle cell (SMC) hypertrophy, we studied the effects of NPY on proliferation of cultured rat aorta- and vena cava-derived SMC. Both cell types displayed high-affinity NPY binding sites with displacement characteristics of [Pro34]NPY > NPY(13-36) > NPY(18-36) in aorta and [Pro34]NPY = NPY(13-36) = NPY(18-36) in the vena cava. Incubation with NPY (50-1000 nM) for 48 h increased by up to twofold cell number and [3H]-thymidine incorporation in both cell types (aortic more sensitive to NPY than venous). Following incubation with NPY, the disappearance of NPY immunoreactivity (-IR) from media was markedly delayed in the presence of SMC, and cell content of NPY-IR increased in a dose-dependent manner, indicating that SMC either diminish degradation of the peptide (possibly by internalization) or secrete endogenous NPY (or both). Structure-activity relationship studies with NPY(18-36) indicated involvement of Y1 receptors in mitogenesis. Thus, NPY has a mitogenic effect (probably mediated by Y1 receptors) and, therefore, may be a sympathetic trophic factor involved in vascular hypertrophy.
Zukowska-Grojec
Z
Z
Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC 20007.
Pruszczyk
P
P
Colton
C
C
Yao
J
J
Shen
G H
GH
Myers
A K
AK
Wahlestedt
C
C
D000818:Animals; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D008934:Mitogens / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism / Q000494:pharmacology*; D019894:Peptide YY; D010455:Peptides / Q000378:metabolism; D051381:Rats; D017476:Receptors, Neuropeptide Y / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism
D008934:Mitogens; D009478:Neuropeptide Y; D010455:Peptides; D017476:Receptors, Neuropeptide Y; D019894:Peptide YY; D013936:Thymidine