title: Renal responses to three types of renin-angiotensin system blockers in patients with diabetes mellitus on a high-salt diet:  a need for higher doses in diabetic patients?
abstract: OBJECTIVE
  Activation of the renal renin-angiotensin system in patients with diabetes mellitus appears to contribute to the risk of nephropathy. Recently, it has been recognized than an elevation of prorenin in plasma also provides a strong indication of risk of nephropathy. This study was designed to examine renin-angiotensin system control mechanisms in the patient with diabetes mellitus.
  
  
  METHODS
  We enrolled 43 individuals with type 2 diabetes mellitus. All individuals were on a high-salt diet to minimize the contribution of the systemic renin-angiotensin system. After an acute exposure to captopril (25 mg), they were randomized to treatment with either irbesartan (300 mg) or aliskiren (300 mg) for 2 weeks.
  
  
  RESULTS
  All agents acutely lowered blood pressure and plasma aldosterone, and increased renal plasma flow and glomerular filtration rate. Yet, only captopril and aliskiren acutely increased plasma renin and decreased plasma angiotensin II, whereas irbesartan acutely affected neither renin nor angiotensin II. Plasma renin and angiotensin II subsequently did increase upon chronic irbesartan treatment. When given on day 14, irbesartan and aliskiren again induced the above hemodynamic, renal and adrenal effects, yet without significantly changing plasma renin. Irbesartan at that time did not affect plasma angiotensin II, whereas aliskiren lowered it to almost zero.
  
  
  CONCLUSIONS
  The relative resistance of the renal renin response to acute (irbesartan) and chronic (irbesartan and aliskiren) renin-angiotensin system blockade supports the concept of an activated renal renin-angiotensin system in diabetes, particularly at the level of the juxtaglomerular cell, and implies that diabetic patients might require higher doses of renin-angiotensin system blockers to fully suppress the renal renin-angiotensin system.
authors: Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. dcapone@partners.org
authors: Norman K
authors: NK
authors: Hollenberg
authors: Naomi D L
authors: ND
authors: Fisher
authors: Juerg
authors: J
authors: Nussberger
authors: George V
authors: GV
authors: Moukarbel
authors: Ebrahim
authors: E
authors: Barkoudah
authors: A H Jan
authors: AH
authors: Danser
mesh_terms: D000450:Aldosterone / Q000097:blood; D000577:Amides / Q000627:therapeutic use*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005650:Fumarates / Q000627:therapeutic use*; D006801:Humans; D000077405:Irbesartan; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012084:Renin-Angiotensin System / Q000187:drug effects; D017673:Sodium Chloride, Dietary; D013777:Tetrazoles / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000577:Amides; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D005650:Fumarates; D017673:Sodium Chloride, Dietary; D013777:Tetrazoles; D000450:Aldosterone; C446481:aliskiren; D002216:Captopril; D000077405:Irbesartan