Both the renin-angiotensin system and dietary protein intake influence progression of renal injury. Furthermore, these two factors are themselves interrelated, in that increased protein intake stimulates the renin-angiotensin system. Thus, dietary protein may influence renal function and injury at least, in part through angiotensin's effects on glomeruli and tubules. The current proposal focuses on the interaction of dietary protein with the renin system, and the effects of these two factors on glomerular growth, function, and injury. Four principal areas are addressed. First, the investigators will examine the chronic glomerular effects of angiotensin itself, as well as, angiotensin's role in the glomerular effects of dietary protein. These studies employ glomerular micropuncture, clearance, and light and electron morphometry. Second, they will examine the separate and combined influences of dietary protein and experimental renal diseases on renin and angiotensinogen gene expression. These studies will employ basic molecular genetic techniques for measurement of specific mRNA in two models of progressive glomerular sclerosis, the remnant kidney, and adriamycin-induced nephrosis. Third, the recently emphasized, but unexplained, heterogeneity of glomerular injury and dysfunction will be examined on the single nephron level in the same two disease models. These studies will utilize micropuncture, and in the same nephrons, light microscopic glomerular morphometry and assessment of renin content (by quantitative immunocytology) and renin synthesis (by in situ hybridization). This set of studies is designed to determine the role of internephronal variation of renin in chronic heterogeneous glomerular injury. Fourth, the effect of angiotensin on compensatory and protein induced growth of the glomerulus and its components will be studied. These last investigations will mainly involve light and electron microscopy for glomerular morphometry. In summary, several complementary techniques involving both glomerular function and structure will be marshalled to investigate the roles of angiotensin, dietary protein, and their interactions in inducing glomerular changes in heterogeneous progressive injury.
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