AJP - Renal Physiology, Vol 250, Issue 2 348-F356, Copyright © 1986 by American Physiological Society
Angiotensin II and eicosanoids in the control of glomerular size in the rat and human
L. A. Scharschmidt, J. G. Douglas and M. J. Dunn
We examined the possibility that glomerular prostaglandin E2 (PGE2)
regulates the action of angiotensin II (ANG II) on mesangial contraction
and filtration surface area. Using isolated rat glomeruli we indirectly
assessed mesangial contraction and filtration surface area through
measurements of glomerular planar surface area (GPSA) by image-analysis
microscopy. ANG II reduced GPSA by approximately 20% in human and rat
glomeruli, with threshold concentrations of 1 X 10(-13) M and maximum
effect at 5 X 10(-11) M ANG II. Inhibition of glomerular PG synthesis with
indomethacin or meclofenamate potentiated the threshold response of ANG II
to reduce GPSA. Arachidonic acid (5 micrograms/ml) blunted both the
threshold and the maximum responses of GPSA to ANG II. PGE2, 10(-8) and
10(-9) M, also decreased glomerular contraction to ANG II. Endoperoxide
(EP) analogues decreased GPSA and EP 045, a thromboxane A2 (TXA2) receptor
blocker, eliminated the contractile responses of glomeruli to the EP
analogues. Authentic TXA2, synthesized from sheep platelet microsomes, also
reduced GPSA. We conclude that glomerular products of arachidonate
cyclooxygenation may either relax or contract the mesangium, thereby
preserving or reducing filtration surface area. PGE2 exerts protective
actions to reduce the mesangial contraction of ANG II, primarily through
postreceptor effects. TXA2 may decrease glomerular filtration rate in
certain diseases through direct actions on the mesangium.
