title: ACE and non-ACE pathways in the renal vascular response to RAS interruption in type 1 diabetes mellitus.
abstract: BACKGROUND
  The enormous contribution of renin-angiotensin system (RAS) interruption with ACE (angiotensin-converting enzyme) inhibitors and angiotensin II receptor blockers (ARB) in the treatment of diabetic nephropathy has led to interest in the factors involved in angiotensin II (Ang II) generation. In normal subjects, RAS interruption using an ARB produced a 50% greater renal plasma flow (RPF) rise than with an ACE inhibitor, suggesting a substantial contribution of non-ACE pathways. Moreover, immunohistochemistry studies in kidneys of overtly proteinuric diabetic subjects showed up-regulation of chymase, an alternative Ang II-generating enzyme. Our aim was to determine the degree to which the non-ACE pathways contribute to RAS activation in type 1 diabetes mellitus (DM).
  
  
  METHODS
  Type 1 DM patients (N= 37, 14 M/23 F; age 31 +/- 2 years; DM duration 16 +/- 1.7 years; HbA1c 7.7.0 +/- 0.3%) were studied on a high-salt diet. They received captopril 25 mg po one day and candesartan 16 mg po the next day. RPF and glomerular filtration rate (GFR) were measured before and up to 4 hours after drug administration.
  
  
  RESULTS
  Both captopril and candesartan induced a significant rise in RPF (baseline vs. peak <0.0001 for both), and the rise was concordant for the 2 drugs (r= 0.77, P < 0.001). However, the RPF responses were not significantly different between the 2 drugs (captopril 72 +/- 11 mL/min/1.73 m(2), candesartan 75 +/- 12, P= 0.841).
  
  
  CONCLUSIONS
  In predominantly normoalbuminuric, normotensive type 1 DM, activation of the intrarenal RAS reflects a mechanism involving primarily the classic ACE pathway.
authors.affiliation: Department of Medicine, University of Florida, Gainesville, Florida 32610-0226, USA. lansamc@medicine.ufl.edu
authors.forename: M Cecilia
authors.initials: MC
authors.lastname: Lansang
authors.forename: Radomir
authors.initials: R
authors.lastname: Stevanovic
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Price
authors.forename: Lori M B
authors.initials: LM
authors.lastname: Laffel
authors.forename: Norman K
authors.initials: NK
authors.lastname: Hollenberg
mesh_terms: D000328:Adult; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D002216:Captopril / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects*; D012084:Renin-Angiotensin System / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; C081643:candesartan