Proliferation and Na+/H+ exchange activation by endothelin in vascular smooth muscle cells.
Initiation and development of proliferative responses to growth factors are often associated to an activation of the Na+/H+ exchange. The present work examined the effect of endothelin (ET-1) on cell proliferation and Na+/H+ exchange in cultured vascular smooth muscle cells. In rat aortic vascular smooth muscle, ET-1 (0.1 to 10 nmol/L) increased the [3H] thymidine uptake in a dose-dependent manner. This effect was enhanced in presence of insulin (0.1 micrograms/mL to 10 micrograms/mL) as a function of concentration. The Na+/H+ exchange, which is a necessary response for mitogenesis, was dose-dependently stimulated by increasing concentrations of ET-1 (1 to 1000 nmol/L) and presented a biphasic response: a transient acidification followed by a sustained alkalinization. Alkalinization induced by ET-1 was similar to that obtained by the phorbol 12-myristate 13-acetate (PMA). An inhibitor of protein kinase C, H7, or a long-term pretreatment of cells with PMA for 24 h inhibited the effect of ET-1 and PMA on Na+/H+ exchange. These results confirm that ET-1 could act as a growth factor for vascular smooth muscle cells and suggest that its mode of action depends for a large part to protein kinase C activation.
Lonchampt
M O
MO
Institut Henri Beaufour, Les Ulis, France.
Pinelis
S
S
Goulin
J
J
Chabrier
P E
PE
Braquet
P
P
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006863:Hydrogen-Ion Concentration; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D017923:Sodium-Hydrogen Exchangers; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002352:Carrier Proteins; D016232:Endothelins; D017923:Sodium-Hydrogen Exchangers; D004247:DNA; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate