title: Persistent hypertension and progressive renal injury induced by salt overload after short term nitric oxide inhibition.
abstract: BACKGROUND
  Administration of the NO inhibitor N(wdelta)-nitro-L-arginine methyl ester (NAME) and a high-salt diet (HS) promotes severe albuminuria and renal injury, which regresses upon discontinuation of treatments.
  
  
  OBJECTIVE
  We investigated whether these changes reappear after reinstitution of HS, and whether they are prevented by treatment with the antilymphocyte agent mycophenolate mofetil (MMF) or the AT-1 receptor blocker losartan (L). Adult male Munich-Wistar rats received NAME and HS. A control Group (C) received only HS. After 20 days, rats receiving HS and NAME exhibited severe hypertension and albuminuria. After a 30-day recovery period, hypertension was attenuated and albuminuria had virtually disappeared.
  
  
  METHODS
  Rats were then distributed among the following groups: HS, receiving HS; NS, receiving a normal salt (NS) diet; HS-MMF, receiving HS and MMF; HS-LOS, receiving HS and L; HS-HDZ, receiving HS and hydralazine (HDZ). Sixty days later, NS rats showed only slight albuminuria and renal damage or inflammation. In contrast, HS rats developed severe hypertension, marked glomerulosclerosis with interstitial expansion and renal infiltration by macrophages and angiotensin II-positive cells. The group treated with losartan had lowered blood pressure and a lack of albuminuria or renal injury. MMF provided similar protection without altering blood pressure, suggesting a nonhemodynamic effect, a hypothesis reinforced by the finding that HDZ lowered blood pressure without preventing renal injury.
  
  
  RESULTS
  These results indicate that treatment with HS and NAME predisposes to the development of hypertension and renal injury upon salt overload, characterizing a new model of chronic nephropathy.
  
  
  CONCLUSIONS
  The response to MMF or L, but not HDZ, suggests a key role for inflammatory rather than hemodynamic factors.
authors.affiliation: Renal Division, Department of Clinical Medicine, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Ana Lúcia
authors.initials: AL
authors.lastname: Mattar
authors.forename: Flávia Gomes
authors.initials: FG
authors.lastname: Machado
authors.forename: Clarice Kazue
authors.initials: CK
authors.lastname: Fujihara
authors.forename: Denise Maria Avancini Costa
authors.initials: DM
authors.lastname: Malheiros
authors.forename: Roberto
authors.initials: R
authors.lastname: Zatz
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006830:Hydralazine / Q000627:therapeutic use; D006973:Hypertension / Q000139:chemically induced* / Q000517:prevention & control; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D019808:Losartan / Q000627:therapeutic use; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D017673:Sodium Chloride, Dietary / Q000633:toxicity*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D007166:Immunosuppressive Agents; D017673:Sodium Chloride, Dietary; D006830:Hydralazine; D009569:Nitric Oxide; D009173:Mycophenolic Acid; D019808:Losartan