HEMODYNAMIC ROLE OF ARACHIDONATE 12-LIPOXYGENASES AND 5-LIPOXYGENASESIN NEPHROTOXIC SERUM NEPHRITIS

The role of arachidonate 12- and 5-lipoxygenation eicosanoids in media ting acute changes in renal hemodynamics was assessed in nephrotoxic s erum nephritis (NSN) in the rat. Following a single intravenous inject ion of nephrotoxic serum (NTS), significant decrements in glomerular f iltration rate (GFR) and renal blood flow (RBF) occurred at one hour, and were associated with increments in glomerular polymorphonuclear le ukocyte (PMN) counts and in the synthesis of thromboxane (Tx) B2, leuk otriene (LT) B4 and 12-hydroxy-eicosatetraenoic acid (12-HETE). Pretre atment of rats with the arachidonate 12-lipoxygenase inhibitor, baical ein, partially but significantly ameliorated the decrements in GFR and RBF, and blocked the enhanced glomerular synthesis of 12-HETE followi ng administration of NTS. Likewise, pretreatment of rats with the arac hidonate 5-lipoxygenase inhibitor, U-66858, partially ameliorated the decrements in GFR and RBF induced by NTS. Combined pretreatment of rat s with baicalein and U-66858 ameliorated the decrements in GFR and RBF to an extent no different to that of U-66858 alone. In rats pretreate d with the LTB4 receptor antagonist, U-75302, GFR and RBF remained dep ressed to levels no different than in animals which received NTS alone . These observations indicate that in NSN, the acute decrements in GFR and RBF are partially mediated by 12-HETE and arachidonate 5-lipoxyge nation products. Leukotrienes other than LTB4, such as LTD4 and LTC4, are the likely candidates.