EFFECTS OF KW-3635, A SPECIFIC THROMBOXANE A(2)-RECEPTOR ANTAGONIST, ON THE DEVELOPMENT OF LUPUS NEPHRITIS IN NZB-X-NZW F1-MICE

We examined the effect of KW-3635, a specific thromboxane A(2) (TXA(2) )-receptor antagonist, on the development of lupus nephritis in NZB x NZW F1 mice. KW-3635 was orally given once a day for 33 weeks beginnin g at eight weeks of age. In the control group, the mice began to die a t 39 weeks of age, showing severe proteinuria and histopathologic abno rmality in the renal glomeruli. Administration of KW-3635 (30 mg/kg/da y) significantly reduced urinary protein excretion (1.7+/-0.9 vs. 8.5/-2.4 mg/6hr/mouse, P<0.01), mortality (1/18 vs. 6/19, P<0.05) and the histopathologic score of the kidney examined at 41 weeks of age. Thus , chronic administration of KW-3635 markedly attenuated the renal dise ase in NZB x NZW Fl mice, suggesting that TXA(2) is an important media tor of the pathogenesis in this murine model of lupus nephritis.