EFFECT OF DP-1904, A THROMBOXANE A(2) SYNTHASE INHIBITOR, ON PASSIVE HEYMANN NEPHRITIS IN RATS

The antinephritic effect of DP-1904 methyl)-5,6,7,8-tetrahydronaphthal ene-2-carboxylic acid hydrochloride], a thromboxane A(2) synthase inhi bitor, was evaluated using an experimental model of membranous nephrop athy, viz. accelerated passive Heymann nephritis in which the glomerul ar injury is mediated by immune complexes. DP-1904 markedly inhibited the development of glomerular alteration as well as the elevation of p roteinuria and plasma creatinine. When the treatment was started from the 22nd day, at which time proteinuria is fully developed, DP-1904 sh owed beneficial effects on proteinuria and glomerular histopathologica l changes. DP-1904 apparently decreased the deposition of both rabbit immunoglobulin G and rat immunoglobulin G on glomerular basement membr ane in nephritic rats. A single administration of DP-1904 restored the decreased renal tissue blood flow, inhibited glomerular thromboxane B -2 production and increased glomerular prostaglandin E(2) and 6-keto p rostaglandin F-1 alpha production in nephritic rats. These results sug gest that DP-1904 may be an effective agent for the treatment of idiop athic membranous nephropathy and that the beneficial effect of this dr ug may be due to the elimination of glomerular immune deposits and to an increase in renal tissue blood flow related to amelioration of the abnormal metabolism of arachidonic acid.