Increasing the linoleic acid content of the diet leads to a long-term enhanced 2-series prostaglandin and thromboxane synthesis. We have shown a protective effect of a high linoleic acid diet in the partially nephrectomized rat, a model of progressive renal failure and in an immunologic model of glomerulonephritis induced by apoferritin injection in the mouse. This and theoretical considerations on the potential effects of prostaglandins of the 1-series, of the 2 series, and of the 3-series lead us to propose a series of animal experiments with long-term objectives, the aims of which are: 1. To assess the role of dietary supplementation with three different polyunsaturated fatty acids in the prevention renal failure. The three fatty acids chosen are dihommogammalinolenic acid (DHLA) which is known to stimulate synthesis of PGs of the 1-series; linoleic acid (LA) which is known to stimulate synthesis of PGs of the 2-series; and eicosapentaenoic acid (EPA) which is known to stimulate synthesis of the PGs of the 3-series. 2. To assess the role of such dietary stimulation of prostaglandin synthesis in three experimental models of renal failure: (a) the rat with a non-immunologic model of progressive renal failure induced by reducing the renal mass by 3/4-nephrectomy; (b) an experimental model of immune complex glomerulonephritis--apoferritin induced glomerulonephritis in the mouse; (c) diabetic nephropathy induced by streptozotocin in the rat. 3. To determine whether beneficial effects of polyunsaturated fatty acid supplementation of the diet are mediated by prostaglandins and thromboxanes; also to asses the possible influences of the protaglandins and thromboxanes on the adaptive mechanisms which operate as a response to decreases in functional renal mass during the evolution of chronic renal disease to end-stage renal failure. 4. To investigate the possible relationship between the PGs and Txs with other factors which are considered to be pathogenetically important in renal disease, such as the fibrinolytic system and plasma lipid composition.
