title: Low protein diet mediated renoprotection in remnant kidneys: Renal autoregulatory versus hypertrophic mechanisms.
abstract: BACKGROUND
  The mechanism of low protein diet conferred renoprotection in the ablation model remains controversial. Blockade of glomerular hypertrophy, reduced preglomerular vasodilation, and preserved autoregulation have all been postulated. The potential differential impact of calcium channel blockers on these mechanisms and glomerulosclerosis was examined.
  
  
  METHODS
  Rats with 5/6 renal ablation received either a 25% standard protein diet, an 8% low protein diet and a low protein diet with either verapamil or amlodipine. Renal autoregulatory and morphometric studies were performed at 3 weeks before the development of significant injury, and the assessment of glomerulosclerosis after 7 weeks of continuous blood pressure radiotelemetry in additional rats.
  
  
  RESULTS
  The preserved renal autoregulation in low protein rats was abolished by both calcium channel blockers, with the impairment being either comparable to (low protein + verapamil) or greater than the standard protein rats (low protein + amlodipine). Neither calcium channel blocker blocked the inhibitory effects of low protein diet on renal blood flow, kidney weight, and glomerular volume. Results (mean +/- SE) for glomerular volume (microm-3x 10(-6)): low protein (N = 11), 1.6 +/- 0.1; low protein + verapamil (N = 10), 1.7 +/- 0.1; low protein + amlodipine (N = 12), 1.7 +/- 0.2; versus standard protein (N = 10), 2.2 +/- 0.1; P < 0.05. Only amlodipine, but not verapamil, reduced average systolic blood pressure (143 +/- 2 mm Hg versus low protein rats, 168 +/- 5 mm Hg, and standard rats, 170 +/- 6 mm Hg; P < 0.01). Nevertheless, the glomeruloprotection seen in low protein (N = 15) as compared to standard protein (N = 14) rats (9%+/- 3% versus 28%+/- 6% glomerulosclerosis; P < 0.01) was abolished in both low protein + verapamil (N = 14, 32%+/- 7%) and low protein + amlodipine rats (N = 16, 27%+/- 7%).
  
  
  CONCLUSIONS
  Preservation of renal autoregulation and not inhibition of hypertrophy is the critical component in low protein diet-conferred glomeruloprotection.
authors.affiliation: Department of Internal Medicine, Loyola University Medical Center; and Edward Hines, Jr., Hospital, Maywood and Hines, Illinois 60141, USA. Martha.Prado@med.va.gov
authors.forename: Karen A
authors.initials: KA
authors.lastname: Griffin
authors.forename: Maria
authors.initials: M
authors.lastname: Picken
authors.forename: Anita
authors.initials: A
authors.lastname: Giobbie-Hurder
authors.forename: Anil K
authors.initials: AK
authors.lastname: Bidani
mesh_terms: D017311:Amlodipine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D019610:Cytoprotection; D018753:Diet, Protein-Restricted; D006706:Homeostasis / Q000187:drug effects; D006984:Hypertrophy / Q000517:prevention & control; D007668:Kidney / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009392:Nephrectomy / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013686:Telemetry; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D017311:Amlodipine; D014700:Verapamil