AJP - Renal Physiology, Vol 248, Issue 2 240-F246, Copyright © 1985 by American Physiological Society
Vasoconstrictor-evoked prostaglandin synthesis in cultured human mesangial cells
N. Ardaillou, J. Hagege, M. P. Nivez, R. Ardaillou and D. Schlondorff
We examined the influence of angiotensin II (ANG II), arginine vasopressin
(AVP), and platelet activating factor (PAF) on prostaglandin (PG) synthesis
and cell contractility in human glomerular mesangial cells in culture.
Addition of sodium butyrate to the culture medium for 40 h significantly
increased synthesis of both 6-keto-PGF1 alpha and PGE2 in the presence of
exogenous arachidonic acid and of PGE2 under basal conditions. To optimize
conditions in all further experiments, cells cultured with butyrate were
studied. Under basal conditions, cultured mesangial cells produced
predominantly 6-keto-PGF1 alpha and much less PGE2. Addition of either ANG
II, AVP, or PAF all resulted in a rapid (within minutes) two- to threefold
stimulation of 6-keto-PGF1 alpha and PGE2. Threshold stimulations were
obtained at 10 pM for ANG II, 1 nM for AVP, and 10-100 pM for PAF.
Preincubation of the cells with [Sar1,Ala8]ANG II, an antagonist of ANG II,
inhibited ANG II-enhanced PG production, and preincubation with
1-desamino-8-D-arginine vasopressin, an antidiuretic analogue, blunted
AVP-enhanced PG production. Under phase-contrast microscopy, PAF, ANG II,
and, to a lesser degree, AVP caused decrease in cell surface area of
mesangial cells cultured without butyrate at concentrations similar to
those stimulating PG synthesis. Only PAF contracted cells cultured with
butyrate, indicating attenuation of the vasoactive effects of ANG II and
AVP when synthesis of PG was increased. However, a lower dose of PAF was
only active when PG synthesis was inhibited, suggesting the same feedback
mechanism for the three agonists.
