Dietary protein intake modulates glomerular eicosanoid production in the rat

The quantity of protein in the diet modulates glomerular function. To study the effect of dietary protein intake on glomerular eicosanoid production, rats were randomized to either a high- (40%) or low- (8.5%) protein isocaloric diet. Ten to fourteen days later glomeruli were isolated and incubated in the absence (basal) and presence (stimulated conditions) of arachidonic acid, and production rates of prostaglandin (PG) E₂, PGF(2α), and thromboxane B₂ (TxB₂) were determined by direct radioimmunoassay. Under basal conditions, glomerular production of all three eicosanoids was significantly greater in rats ingesting the high-protein diet. Glomerular production of PGE₂ and TxB₂ was also greater in animals fed the high-protein diet in the presence of arachidonic acid, suggesting that glomerular cyclooxygenase activity was augmented. In contrast, ingestion of a high-protein diet was not associated with a significant increase in eicosanoid production by renal papillae or in TxB₂ release by clotting blood. To investigate the potential role of the renin-angiotensin system in the dietary protein-induced modulation of glomerular eicosanoid production, rats ingesting a high- or low-protein diet were randomized to treatment with an angiotensin-converting enzyme inhibitor or no therapy. Enalapril attenuated the dietary protein-induced augmentation in glomerular eicosanoid production. This effect occurred only when administered in vivo, since the active metabolite enalaprilat did not alter PGE₂ production by isolated glomeruli when added in vitro. Dietary protein intake also modulated glomerular eicosanoid production in three models of experimental renal disease in the rat (streptozotocin-induced diabetes mellitus, Heymann nephritis, and partial renal ablation). We conclude that 1) dietary protein modulates glomerular eicosanoid synthesis in the rat, and 2) this effect appears to require a functioning renin-angiotensin system.