title: Prevention of hypertension with or without renin-angiotensin system inhibition precludes nephrin loss in the early stage of experimental diabetes mellitus.
abstract: OBJECTIVE
  Several lines of clinical evidence support the concept that the reduction of blood pressure may be useful in the prevention of diabetic kidney disease. In young diabetic spontaneously hypertensive rats (SHR), prevention of hypertension reduces several early renal abnormalities including albuminuria. However, the contribution of nephrin loss to albuminuria in this early stage of experimental diabetes is unknown. Therefore, we investigated whether elevation of albuminuria in young diabetic SHR is associated with nephrin loss, and if prevention of hypertension, with or without inhibition of the renin-angiotensin system, precludes these abnormalities.
  
  
  METHODS
  Diabetes was induced by streptozotocin injection in 4-week-old still normotensive SHR and their genetically normotensive control, Wistar-Kyoto rats. Diabetic SHR were randomized for no treatment, or treatment with captopril, losartan, or triple therapy (hydrochlorothiazide, reserpine and hydralazine) for 20 days.
  
  
  RESULTS
  The increase in systolic blood pressure was equally prevented by all treatments. Albuminuria was higher in diabetic SHR and similarly reduced (p < 0.05) by captopril, losartan, and triple therapy. Glomerular expression of nephrin was significantly reduced in diabetic SHR in comparison with non-diabetic controls. The antihypertensive treatment prevented the reduction in glomerular expression of nephrin.
  
  
  CONCLUSIONS
  These results demonstrate that the loss of nephrin is associated with albuminuria in a model of genetic hypertension and diabetes, and that the prevention of development of hypertension restores nephrin and prevents albuminuria. This finding suggests a crucial role of blood pressure in diabetes as determinant of nephrin expression and albuminuria.
authors: Laboratory of Renal Pathophysiology, Nephrology Unit, State University of Campinas (UNICAMP), Campinas, SP, Brazil.
authors: Roberto Bleuel
authors: RB
authors: Amazonas
authors: Rodrigo de Almeida
authors: Rde A
authors: Sanita
authors: Hiroshi
authors: H
authors: Kawachi
authors: José B Lopes
authors: JB
authors: de Faria
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000517:prevention & control*; D006973:Hypertension / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
chemical_list: D000959:Antihypertensive Agents; D008565:Membrane Proteins; C113267:nephrin