AJP - Renal Physiology, Vol 250, Issue 5 838-F844, Copyright © 1986 by American Physiological Society
Effects of leukotrienes on isolated rat glomeruli and cultured mesangial cells
R. Barnett, P. Goldwasser, L. A. Scharschmidt and D. Schlondorff
Several vasoactive substances influence glomerular function in vivo and
alter glomerular surface area and prostaglandin (PG) synthesis in vitro.
Leukotrienes (LT) LTC4 and LTD4 may also influence glomerular function in
vivo and in the isolated perfused kidney. We therefore compared the effects
of LT with those of angiotensin II (ANG II), arginine vasopressin (AVP),
and platelet activating factor (PAF) on planar surface area of isolated rat
glomeruli and the shape change of cultured mesangial cells and their PG
synthesis. ANG II, AVP, and PAF decreased the surface area of isolated rat
glomeruli by 10-14% with comparable changes induced by LTC4 and LTD4.
Half-maximal effects of LTs were observed at approximately 10(-7) M.
Incubation of cultured rat mesangial cells with LTC4 or LTD4 at 10(-7) and
10(-8) M was also associated with shape changes of the cells resulting in
significant reductions in planar surface area in a dose- and time-dependent
fashion similar to that noted previously with other vasoactive agents. In
cells grown on a flexible silicone rubber support, LTD4 resulted in rapid
increases in wrinkling of the mobile surface indicating that the shape
change may represent cell contraction. The LT-mediated decrease in surface
area of glomeruli and mesangial cells was partially antagonized by the LT
inhibitor FPL-55712. In contrast to the 11- and 7-fold enhancement of PGE2
synthesis in cultured mesangial cells by ANG II or PAF, neither LTC4 nor
LTD4 affected PGE2 production. These results demonstrate that LTC4 and LTD4
cause mesangial shape changes that in the whole glomerulus may decrease
glomerular surface area.(ABSTRACT TRUNCATED AT 250 WORDS)
