The aim of the present study was to investigate the effect of arginine [Arg(8)]vasopressin (vasopressin) on proliferation of vascular smooth muscle cells and the mechanisms underlying the action of vasopressin. To clarify these issues, we used two different types of vascular smooth muscle cells, cultured adult rat aortic smooth muscle cells and A10 cells, a cell line derived from fetal rat aorta. Vasopressin (10(-8) to 10(-6) M) significantly stimulated the proliferation of rat aortic smooth muscle cells in a dose-dependent manner. In contrast, vasopressin significantly inhibited the proliferation of A10 cells. This inhibition was abolished when A10 cells were treated with indomethacin. Vasopressin stimulated the production of prostanoids several-fold in A10 cells but not in rat aortic smooth muscle cells. These effects were completely blocked by the vasopressin V-1 receptor antagonist, 1-{1-[4-(3-acetylamino-propoxy)benzoyl]4-piperidyl)-3,4-dihydro-2(1H)-quinolinone (OPC21268), but not by the vasopressin V-2 receptor antagonist, (+/-)-5-dimethylamino-1-[4-(2-methylbenzoylamino)benzol]-2,3,4,5-tetrahydro-1H-benzazepine hydrochloride (OPC31260). These results indicate that vasopressin has diverse effect on proliferation of vascular smooth muscle cells through the vasopressin V-1 receptor, depending on the production of growth regulatory prostanoids. (C) 2000 Elsevier Science B.V. All rights reserved.