title: Direct renin inhibition exerts an anti-hypertrophic effect associated with improved mitochondrial function in post-infarction heart failure in diabetic rats.
abstract: BACKGROUND
  In addition to hypertension control, direct renin inhibition has been shown to exert direct beneficial effects on the heart in post-infarction cardiac remodeling. This study elucidates the possible contribution of mitochondria to the anti-hypertrophic effects of the direct renin inhibitor aliskiren in post-infarction heart failure complicated with diabetes in rats.
  
  
  METHODS
  Diabetes was induced in male Sprague-Dawley rats by a single injection of streptozotocin (IP, 65 mg/kg body weight). After 7 days, the animals were randomly assigned to 4 groups: sham, heart failure, sham+aliskiren, and heart failure+aliskiren. Post-infarction HF was induced by coronary artery ligation for 4 weeks.
  
  
  RESULTS
  showed that heart failure reduced ejection fraction and cardiac output by 41% (P<0.01) and 42% (P<0.05), respectively, compared to sham-operated hearts. Cardiac dysfunction was associated with suppressed state 3 respiration rates and respiratory control index in mitochondria, and increased mitochondrial permeability transition pore (PTP) opening. In addition, heart failure reduced expression of the major mitochondrial sirtuin, SIRT3 and increased acetylation of cyclophilin D, a regulatory component of the PTP. Aliskiren significantly improved cardiac function and abrogated mitochondrial perturbations.
  
  
  CONCLUSIONS
  Our results demonstrate that aliskiren attenuates post-infarction remodeling which is associated with its beneficial effects on mitochondria.
authors.affiliation: Department of Physiology, School of Medicine, University of Puerto Rico, San Juan, PR, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Parodi-Rullan
authors.forename: Giselle
authors.initials: G
authors.lastname: Barreto-Torres
authors.forename: Louis
authors.initials: L
authors.lastname: Ruiz
authors.forename: José
authors.initials: J
authors.lastname: Casasnovas
authors.forename: Sabzali
authors.initials: S
authors.lastname: Javadov
mesh_terms: D000577:Amides / Q000627:therapeutic use; D000818:Animals; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004452:Echocardiography; D004591:Electrophoresis, Polyacrylamide Gel; D005650:Fumarates / Q000627:therapeutic use; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D008929:Mitochondria, Heart / Q000502:physiology*; D009203:Myocardial Infarction / Q000150:complications*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D005650:Fumarates; D000092502:Renin Inhibitors; C446481:aliskiren