Date of Graduation


Document Type



Chronic renal disease is the progressive loss of renal function that can lead to end-stage renal disease. Recent studies from our laboratory have shown decreased total NO production in patients with renal disease. Animal models have shown decreased total and renal NO production and chronic NOS inhibition in otherwise healthy rats causes renal injury. The overall objective in this set of studies was to investigate intrarenal NO production in various models of CRD and determine if NO deficiency parallels, and perhaps causes renal injury. In the first study, we report that normal male SD rats exhibit age-dependent declines in total NO production and cortical NOS activity and constitutive NOS abundance. Increasing glomerular injury parallels the decline in NO production. Conversely, females do not develop age-dependent injury or declines in renal function. In comparison to males, females have maintained total NO production and cortical NOS activity and constitutive NOS abundance. In the second study we investigated the rapidly developing model of CRD secondary to 5/6th ablation/infarction (A/I) of renal mass. Wistar Furth (WF) rats do not develop rapidly progressing CRD following A/I compared to the SD. The hypothesis tested was WF rats have an elevated NO system vs SD that protects from CRD due to A/I. In support of previous studies, SD developed severe proteinuria and decreased renal function as compared to the WF. SD rats had severely decreased total NO production (NOx) compared to shams following renal mass reduction. WF rats have elevated baseline total NO production vs SD that persists through 11 weeks. Also, WF A/I progresses no differently than a WF sham in total NO production indicating maintained NO production. Cortical nNOS abundance is reduced in both the WF and SD rats but WF shams have elevated baseline nNOS and WF A/I is similar to a SD sham. Renal medulla nNOS is not decreased in WF while SD rats exhibit a significant decline. Renal eNOS abundance is relatively unchanged in these two strains. Cortical NOS activity in shams was elevated in the SD compared to WF.