MODIFICATION OF MESANGIAL CELL-FUNCTION BY CHLORIDE IS ATTENUATED IN SPONTANEOUSLY HYPERTENSIVE RATS

The effects of extracellular Cl- concentration ([Cl-](0)) on cultured mesangial cells from spontaneously hypertensive rats (SHR) were examin ed. Angiotensin II (ANG II)- and vasopressin (VP)-induced cell contrac tion and Ca2+ transients of SHR mesangial cells were unaffected when t he cells were preincubated with 10 mM [Cl-](0), while obvious suppress ion of the responses to these agents was observed in Wistar-Kyoto (WKY ) mesangial cells. Enhanced prostaglandin E(2) (PGE(2)) production was elicited by a decrease in [Cl-](0) in WKY mesangial cells. In contras t, PGE(2) synthesis by SHR mesangial cells was not enhanced by low [Cl -](0). However, ANG II-stimulated PGE(2) production and the attenuatio n of ANG II-induced cell. contraction and Ca2+ transients by the addit ion of exogenous PGE(2) were present equally in both WKY and SHR mesan gial cells. Based on these findings, we conclude that the absence of m odification of mesangial cell function by [Cl-](0) in SHR is due to th e inability of low [Cl-](0) to enhance PGE(2) production. Insensitivit y of SHR mesangial cells to changes in [Cl-](0) might underlie the dys regulation of renal function in SHR.