AJP - Renal Physiology, Vol 266, Issue 4 586-F591, Copyright © 1994 by American Physiological Society
Modification of mesangial cell function by chloride is attenuated in spontaneously hypertensive rats
T. Okuda, Y. Inishi, T. Arakawa, M. Ohara and K. Kurokawa
First Department of Internal Medicine, University of Tokyo Faculty of Medicine, Japan.
The effects of extracellular Cl- concentration ([Cl-]o) on cultured
mesangial cells from spontaneously hypertensive rats (SHR) were examined.
Angiotensin II (ANG II)- and vasopressin (VP)-induced cell contraction and
Ca2+ transients of SHR mesangial cells were unaffected when the cells were
preincubated with 10 mM [Cl-]o, while obvious suppression of the responses
to these agents was observed in Wistar-Kyoto (WKY) mesangial cells.
Enhanced prostaglandin E2 (PGE2) production was elicited by a decrease in
[Cl-]o in WKY mesangial cells. In contrast, PGE2 synthesis by SHR mesangial
cells was not enhanced by low [Cl-]o. However, ANG II-stimulated PGE2
production and the attenuation of ANG II-induced cell contraction and Ca2+
transients by the addition of exogenous PGE2 were present equally in both
WKY and SHR mesangial cells. Based on these findings, we conclude that the
absence of modification of mesangial cell function by [Cl-]o in SHR is due
to the inability of low [Cl-]o to enhance PGE2 production. Insensitivity of
SHR mesangial cells to changes in [Cl-]o might underlie the dysregulation
of renal function in SHR.
