Arginine vasopressin promotes growth of rat glomerular mesangial cells in culture

Abstract

Arginine vasopressin (AVP) binds specifically to vascular smooth muscle-like mesangial cells (MCs) and affects contraction. We 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 (10(-10)-10(-6) M) in the presence or absence of insulin (5 micrograms/ml). To assess DNA replication, MC uptake of [3H]thymidine (24-h pulse) 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-(beta-mercapto-beta,beta-cyclopentamethylene proprionic acid), 2-(O-methyl-Tyr)-Arg]vasopressin (PMP) inhibited only AVP-induced promotion of MC growth (maximal inhibition of -78.3%). The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) acutely stimulated MC proliferation but did not add to the AVP effect. Preincubation of MCs with 600 nM of TPA for 48 h significantly inhibited AVP-induced mitogenesis (-87.2%). By use of fura-2, intracellular calcium (Cai) was assessed by spectrofluorometry. The addition of AVP (10(-12)-10(-6) M) led to a rapid, transient, dose-dependent increase in Cai of 154-383%, respectively. The AVP-induced increase in Cai was greatly inhibited by 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester hydrochloride (TMB-8) (10(-8)-10(-6) M), an inhibitor of Cai release (-23.9 to -72.1%), and it was blunted by the atrial natriuretic peptide AP-28 (-38.3%).(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine vasopressin stimulates human mesangial cell production of endothelin.

“…We further support the finding that insulin augments for the mitogenic effect of ET on these cells (7). Furthermore, the dose and time course over which this occurred is similar to previous reports (15). In addition, our data confirm previous reports that selective inhibition of V1 receptors attenuates the mitogenic response of vasopressin in the presence and absence of insulin (15,16).…”

“…AVP increased mesangial cell proliferation in a dose-dependent fashion ( Figs. 3 and 4 (15). We further support the finding that insulin augments for the mitogenic effect of ET on these cells (7).…”

“…Previous studies also show that insu- lin, at a dose used in our study, potentiates the mitogenic effects of various vasoactive peptides on mesangial cells, although insulin by itself is a relatively weak mitogen in comparison to these peptides (15,(26)(27). Furthermore, the action of various mitogenic peptides such as AVP or angiotensin II on mesangial cells is markedly blunted or absent ifinsulin is not present in the culture milieu (15,28,29). Our data support these findings in that insulin potentiates the mitogenic effect ofAVP in HMC.…”

Correlates of aldosterone-induced increases in Cai2+ and Isc suggest that Cai2+ is the second messenger for stimulation of apical membrane conductance.

“…Estimates ofthe activity of Ca42+ were made with Fura-2/AM (5 MM) using a model LS-5B spectrofluorometer (Perkin-Elmer Corp., Pomona, CA) as previously reported by this laboratory (13). In these experiments Caj2 was estimated by measuring the ratio offluorescence of emitted light at 510 nm after excitation at 340 and 380 nm (14).…”

Low density lipoprotein enhances the cellular action of arginine vasopressin in rat glomerular mesangial cells in culture.

“…Since cellular alkalinization enhances cell contraction, cellular growth, etc, in glomerular mesangial cells (2,5,36), it is of great value to elucidate the mechanisms for the …”