Contractile effects of TxA2 and endoperoxide analogues on cultured rat glomerular mesangial cells

Abstract

Vasoconstrictor metabolites of arachidonic acid (AA) affect renal hemodynamics in various disease models. Since mesangial contraction could be involved in the glomerular response to vasoconstrictors, we studied the effects of thromboxane A2 (TxA2), synthesized by sheep platelet microsomes, and of two stable prostaglandin (PG) endoperoxide analogues (END), U-44069 and U-46619, on the morphology of cultured rat mesangial cells. Computer-assisted image analysis microscopy was employed to measure cross-sectional area (CSA) of individual cells during 40-min incubations with the agonists. Both END induced a dose-dependent increase of contracting cells (U-44069, 1 pM, 14.2%; 1 nM, 25.0%; 1 microM, 34.4%; maximum CSA decrease, 16.6 +/- 2.9%; U-46619, 1 pM, 11.4%; 1 nM, 25.6%; 1 microM, 37.2%; maximum CSA decrease, 23.6 +/- 2.2%). TxA2 contracted 30.1% of the cells, with a maximum CSA decrease of 20.5 +/- 2.4%. The TxA2-receptor antagonists EP 092 (EP) and SQ 27,427 (SQ) significantly (P less than 0.05) reduced the number of cells contracting in response to U-44069 (+EP 7.3%, +SQ 10.8%) or U-46619 (+EP 14.2%, +SQ 11.1%), and eliminated TxA2-induced contraction. END also stimulated mesangial immunoreactive prostaglandin E2 (PGE2) synthesis (U-44069, 1 nM, from 2.17 +/- 0.62 to 4.36 +/- 1.0; U-46619, 1 nM, from 2.09 +/- 0.64 to 5.05 +/- 1.04, ng X mg protein-1 X 15 min-1 +/- SE). These results suggest that mesangial contraction, with resulting reduction of filtration surface area, may contribute to the effects of TxA2 and endoperoxides on glomerular hemodynamics.