DOCA/NaCl-induced chronic kidney disease: a comparison of renal nitric oxide production in resistant and susceptible rat strains.
Erdely-A; Freshour-G; Tain-YL; Engels-K; Baylis-C
Am J Physiol Renal Physiol 2007 Jan; 292:F192-F196
Recent studies show nitric oxide (NO) deficiency is both a cause and consequence of chronic kidney disease (CKD). Reduced renal neuronal NO synthase (nNOS) abundance and activity parallel development of CKD with different models in the Sprague-Dawley (SD) rats, whereas Wistar Furth (WF) rats are protected against CKD and show preserved renal NO production. In this study, we compared renal NO in response to DOCA/salt-induced injury between the WF and SD. Studies were conducted on sham WF (n = 6) and SD (n = 6) and uninephrectized (UNX) + 75 mg DOCA + 1% NaCl (WF n = 9; SD n = 10) rats followed for 5 wk. Kidneys were harvested for Western blot, NOS activity, and histology. Other measurements included creatinine clearance and 24-h total NO production and urinary protein excretion. Absolute values of kidney weight were lower in WF than SD rats that showed similar percent increases with UNX + DOCA/NaCl. Proteinuria and decreased creatinine clearance were present in the SD but not the WF rats following UNX + DOCA/NaCl. Glomerular injury was mild in the WF compared with SD rats that showed many globally damaged glomeruli. Although renal nNOS abundance was decreased in both strains (higher baseline in WF), soluble NOS activity was maintained in the WF but significantly reduced in the SD rats. Renal endothelial NOS abundance and membrane NOS activity were unaffected by treatment. In summary, WF rats showed resistance to UNX + DOCA/NaCl-induced CKD with maintained renal NO production despite mild reduction in nNOS abundance. Further studies are needed to evaluate how WF rats maintain renal NO production despite similar changes in abundance as the vulnerable SD strain.
Exposure-assessment; Exposure-levels; Exposure-methods; Animal-studies; Urinalysis; Urine-chemistry; Renal-absorption; Renal-toxicity; Cell-metabolism; Cell-damage; Cellular-uptake; Laboratory-animals
C Baylis, Dept. of Physiology and Functional Genomics, 1600 SW Archer Rd., PO Box 100274, Univ. of Florida, Gainesville, FL 32610-0274
American Journal of Physiology: Renal Physiology