Vasopressin increases vascular endothelial growth factor secretion from human vascular smooth muscle cells.
Vascular endothelial growth factor (VEGF) is a potent and specific mitogen of vascular endothelial cells which promotes neovascularization in vitro. To determine whether vasopressin induces VEGF secretion in human vascular smooth muscle cells, we performed enzyme-linked immunosorbent assays. Vasopressin potently induced a time-dependent and concentration-dependent (maximal, 10(-7) M) increase in VEGF secretion by human vascular smooth muscle cells that was maximal after 24 h. Furthermore, vasopressin also concentration-dependently caused mitogenic effect, as reflected by total protein content of cells per culture well. These vasopressin-induced VEGF secretion increase and mitogenic effect of these cells were potently inhibited by vasopressin V1A receptor antagonists, confirming this is a vasopressin V1A receptor-mediated event. These results indicate that vasopressin increases VEGF secretion in human vascular smooth muscle cells, the magnitude of VEGF secretion being temporally related to the mitogenic effect of vascular smooth muscle cells and the potency of the growth-promoting stimulus. Vasopressin-induced VEGF secretion by proliferating vascular smooth muscle cells could act as a paracrine hormone to powerfully influence the permeability and growth of the overlying vascular endothelium, vasopressin play a more fundamental role in the regulation of vascular function than has previously been recognized.
Tahara
A
A
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical, Tsukuba, Ibaraki, Japan. tahara@yamanouchi.co.jp
Saito
M
M
Tsukada
J
J
Ishii
N
N
Tomura
Y
Y
Wada
K
K
Kusayama
T
T
Yatsu
T
T
Uchida
W
W
Tanaka
A
A
D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines / Q000494:pharmacology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D016228:Endothelial Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008222:Lymphokines / Q000378:metabolism / Q000494:pharmacology*; D009025:Morpholines / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology; D013141:Spiro Compounds / Q000494:pharmacology; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014667:Vasopressins / Q000494:pharmacology*
D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D016228:Endothelial Growth Factors; D007211:Indoles; D008222:Lymphokines; D009025:Morpholines; D011759:Pyrrolidines; D013141:Spiro Compounds; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014662:Vasoconstrictor Agents; C106389:conivaptan; D014667:Vasopressins; C103281:satavaptan; C082134:relcovaptan