Arginine vasopressin promotes growth of rat glomerular mesangial cells in culture

Arginine vasopressin (AVP) binds specifically to vascular smooth muscle-like mesangial cells (MCs) and affects contraction. The authors tested whether this peptide also modulates growth behavior of rat MCs in early subculture (passage 2-5). Subconfluent, serum-starved MCs were exposed to AVP in the presence or absence of insulin. To assess DNA replication, MC uptake of [3H]thymidine was determined on days 1, 2, and 3. AVP alone averaged a 1.97-fold increase in DNA synthesis at 24 h, whereas the mean stimulatory effects of AVP at 48 and 72 h were 7.21- and 5.42-fold, respectively. MCs exposed simultaneously to AVP and insulin showed potentiation of the mitogenic response to AVP alone. The V1-receptor antagonist [1-(β-mercapto-β,β-cyclopentamethylene proprionic acid), 2-(O-methyl-Tyr)-Arg]vasopressin (PMP) inhibited only AVP-induced promotion of MC growth. The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) acutely stimulated MC proliferation but did not add to the AVP effect. They conclude that (1) AVP is strongly and specifically mitogenic for rat MCs, (2) the proliferative effect of AVP is mediated by TPA-like activation of protein kinase C, and (3) a maximal rise of Cai need not be essential for the induction of AVP-elicited mitogenesis of MCs