title: Cigarette smoke condensate aggravates renal injury in the renal ablation model.
abstract: BACKGROUND
  Cigarette smoking increases the risk of progression of diabetic and non-diabetic renal diseases. The mechanisms underlying the adverse effects of smoking are largely unknown. We examined the subtotally nephrectomized rat (i) to investigate whether components of cigarette smoke dissolved in acetone (cigarette smoke condensate) aggravate structural renal damage and (ii) to establish whether this provides an animal model that can be used to investigate potential pathomechanisms of cigarette smoke-induced renal damage. Since nicotine activates the sympathetic nerve system in humans, we investigated whether interference with this system modulates the effects of cigarette smoke condensate on the damaged kidney.
  
  
  METHODS
  One group of Sprague-Dawley rats was subtotally nephrectomized (SNX). Acetone (SNX + solvent) or cigarette smoke condensate (SNX + cigarette) was applied daily to the oral mucosa. Another group of Sprague-Dawley rats was sham-operated and received the same treatments (sham + solvent, sham + cigarette). To investigate whether increased activity of the sympathetic nerve system is involved, the remnant kidney was denervated by microsurgical technique in one SNX + cigarette group. The control group for this intervention was a solvent-treated SNX group with denervated remnant kidney. Blood pressure (BP) was measured weekly by tail plethysmography. The experiment was terminated after 12 weeks. Structural renal damage was assessed by morphometric techniques (indices of glomerulosclerosis, tubulointerstitial and vascular damage) and urinary albumin and endothelin-1 excretion were measured.
  
  
  RESULTS
  Indices of structural renal damage were increased in all SNX-groups. Treatment with cigarette smoke condensate further increased the indices of glomerulosclerosis and tubulointerstitial damage in SNX, but not sham-operated rats. This increase was completely prevented by renal denervation. No differences in systemic blood pressure were observed in the different SNX groups. Urinary albumin excretion went in parallel with the indices of glomerulosclerosis and tubulointerstitial damage and urinary endothelin-1 excretion was significantly increased in SNX + cigarette animals.
  
  
  CONCLUSIONS
  These findings document that acetone soluble components in cigarette smoke aggravate glomerulosclerosis and tubulointerstitial damage in the renal ablation model. Renal injury induced by cigarette smoke condensate in this model is reversed by renal denervation. We conclude that cigarette smoke-induced renal damage is due, at least in part, to activation of the sympathetic nerve system.
authors.affiliation: Department of Internal Medicine, Ruperto Carola University, Heidelberg, Germany.
authors.forename: Giulio
authors.initials: G
authors.lastname: Odoni
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ogata
authors.forename: Christiane
authors.initials: C
authors.lastname: Viedt
authors.forename: Kerstin
authors.initials: K
authors.lastname: Amann
authors.forename: Eberhard
authors.initials: E
authors.lastname: Ritz
authors.forename: Stephan R
authors.initials: SR
authors.lastname: Orth
mesh_terms: D000419:Albuminuria / Q000652:urine; D000818:Animals; D002784:Cholesterol / Q000097:blood; D003367:Cotinine / Q000652:urine; D003404:Creatinine / Q000097:blood; D019332:Endothelin-1 / Q000652:urine; D005923:Glomerulosclerosis, Focal Segmental / Q000473:pathology* / Q000503:physiopathology; D007668:Kidney / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D009392:Nephrectomy / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012906:Smoke / Q000009:adverse effects*; D013564:Sympathetic Nervous System / Q000503:physiopathology; D014026:Nicotiana; D014280:Triglycerides / Q000097:blood; D014508:Urea / Q000097:blood
chemical_list: D019332:Endothelin-1; D012906:Smoke; D014280:Triglycerides; D014508:Urea; D002784:Cholesterol; D003404:Creatinine; D003367:Cotinine