title: DOCA/NaCl-induced chronic kidney disease: a comparison of renal nitric oxide production in resistant and susceptible rat strains.
abstract: 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.
authors.affiliation: Department of Physiology and Pharmacology, West Virginia University, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Erdely
authors.forename: Gary
authors.initials: G
authors.lastname: Freshour
authors.forename: You-Lin
authors.initials: YL
authors.lastname: Tain
authors.forename: Kevin
authors.initials: K
authors.lastname: Engels
authors.forename: Chris
authors.initials: C
authors.lastname: Baylis
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D003404:Creatinine / Q000378:metabolism; D003900:Desoxycorticosterone; D004791:Enzyme Inhibitors / Q000633:toxicity; D007676:Kidney Failure, Chronic / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism*; D009392:Nephrectomy; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011507:Proteinuria / Q000139:chemically induced; D011691:Puromycin; D051381:Rats; D011920:Rats, Inbred WF; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride; D013045:Species Specificity
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D011691:Puromycin; D003404:Creatinine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I