Endothelin is a potent mitogen for rat vascular smooth muscle cells.
The effect of endothelin (ET), a novel endothelium-derived vasoconstrictive peptide, on DNA synthesis was studied in cultured rat vascular smooth muscle cells (VSMC). ET stimulated incorporation of [3H]thymidine into DNA of the quiescent VSMC in a dose-dependent manner; the approximate half-maximal and maximal stimulation for DNA synthesis was induced with 2 x 10(-10) M and 10(-9) M, respectively. The stimulatory effect by ET on DNA synthesis was completely inhibited by the calcium channel blocker nifedipine. ET combined with epidermal growth factor and transforming growth factor-alpha, but not with platelet-derived growth factor, had synergistic effects. These data indicate that ET is a potent mitogen as well as a constrictor for VSMC, suggesting its potential role in the development of vascular disease.
Hirata
Y
Y
Second Department of Internal Medicine, Tokyo Medical and Dental University, Japan.
Takagi
Y
Y
Fukuda
Y
Y
Marumo
F
F
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D016232:Endothelins; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D016232:Endothelins; D010455:Peptides; D014662:Vasoconstrictor Agents; D004247:DNA; D009543:Nifedipine