Effects of genetic obesity on renal structure and function in the Zucker rat. II. Micropuncture studies

The obese Zucker rat is a model of nonimmune glomerular disease characterized by spontaneous proteinuria and focal glomerulosclerosis. Mechanisms important in the pathogenesis of glomerular injury in obese Zucker rats are unknown, but may involve hemodynamic and metabolic factors. Micropuncture studies of superficial nephron function were performed prior to the development of FGS in male obese Zucker rats and lean littermates 9 to 13 weeks of age. Compared with lean littermates, obese Zucker rats demonstrated small increases in superficial nephron glomerular filtration rate (32.3 +/- 2.3 nl/min vs. 27.8 +/- 2.0, P greater than 0.05) and plasma flow (87.1 +/- 7.2 nl/min vs. 79.0 +/- 5.1, P greater than 0.05). Intraglomerular hydraulic pressures were not significantly different between groups. Despite similarities in superficial nephron glomerular function, obese Zucker rats displayed increases in glomerular area and mesangial matrix. These morphologic changes occurred in both superficial and deep nephrons. We conclude that increases in glomerular pressures and flows are not a prerequisite for the initiation of glomerular injury in the obese Zucker rat.