title: Direct renin inhibition improves parasympathetic function in diabetes.
abstract: OBJECTIVE
  The renin-angiotensin-aldosterone system (RAAS) and autonomic nervous system regulate the cardiovascular system. Blockade of the RAAS may slow the progression of end-organ damage. Direct renin inhibition offers a means for blocking the RAAS. The objective of this study was to examine the effect of direct renin inhibition on cardiovascular autonomic function.
  
  
  METHODS
  In this double-blind, placebo-controlled trial, 60 individuals with diabetes were randomly assigned to 300 mg of aliskiren or placebo once daily for 6 weeks. The primary end point was a change in tests of cardiovascular autonomic function. Autonomic function was assessed by power spectral analysis and RR-variation during deep breathing [i.e. mean circular resultant (MCR), expiration/inspiration (E/I) ratio]. The MCR and E/I ratio assess parasympathetic function. Secondary measures included change in biochemical parameters [e.g. plasma renin activity, leptin and interleukin-6]. Change in cardiovascular autonomic function and blood analytes were analysed by a mixed effects model for repeated measures.
  
  
  RESULTS
  Baseline characteristics were similar between treatment groups. In response to aliskiren compared with placebo, blood pressure was reduced as well as plasma renin activity [from 2.4 ± 3.8 (mean ± standard deviation) to 0.5 ± 0.4 µg/l/h, p < 0.001]. There was a significant interaction (aliskiren × visit) for MCR (p = 0.003) and E/I ratio (p = 0.003) indicating improvement in MCR and E/I ratio for those on aliskiren. MCR means, baseline vs. follow-up, were 41.8 ± 19.7 vs. 50.8 ± 26.1 (aliskiren) and 38.2 ± 23.6 vs. 37.5 ± 24.1 (placebo).
  
  
  CONCLUSIONS
  Parasympathetic function (i.e. MCR and E/I ratio) was enhanced by downregulation of the RAAS.
authors: Department of Medical Laboratory Sciences, University of Delaware, Newark, DE 19716, USA. rmaser@udel.edu
authors: R E
authors: RE
authors: Maser
authors: M J
authors: MJ
authors: Lenhard
authors: P
authors: P
authors: Kolm
authors: D G
authors: DG
authors: Edwards
mesh_terms: D000577:Amides / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005650:Fumarates / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D010276:Parasympatholytics / Q000494:pharmacology*; D012083:Renin / Q000494:pharmacology; D012084:Renin-Angiotensin System / Q000187:drug effects*; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D005650:Fumarates; D015850:Interleukin-6; D010276:Parasympatholytics; D012083:Renin; D000092502:Renin Inhibitors; C446481:aliskiren