title: Short-term statin administration in hypercholesterolaemic rabbits resistant to postconditioning: effects on infarct size, endothelial nitric oxide synthase, and nitro-oxidative stress.
abstract: OBJECTIVE
  The effectiveness of postconditioning (POC) in hypercholesterolaemia is in dispute. We investigated the effects of 3-day lipophilc (simvastatin) or hydrophilic (pravastatin) statin treatment, without or with POC in normocholesterolaemic (Norm) and hypercholesterolaemic (Chol) rabbits.
  
  
  RESULTS
  Norm or Chol rabbits were subjected to 30 min ischaemia and randomized in two series of 12 groups each: control, simvastatin (Sim), pravastatin (Prav), POC, Sim-POC, Prav-POC, Chol, Sim-Chol, Prav-Chol, POC-Chol, Sim-POC-Chol, Prav-POC-Chol. After ischaemia, rabbits of the first series underwent 3 h reperfusion, followed by infarct size, total cholesterol, and low density lipoprotein plasma level evaluation; animals of the second series underwent 10 min reperfusion followed by tissue sampling for nitrotyrosine (NT), malondialdehyde, endothelial nitric oxide synthase (eNOS), and Akt analyses. N-nitro-l-arginine methylester (L-NAME) was given in two additional groups (POC-L-NAME and Prav-Chol-L-NAME) for infarct size assessment. All interventions reduced infarction in Norm (24.3 ± 1.3, 25.9 ± 2.8, 27.9 ± 3.1, 23.3 ± 2.3, and 33.4 ± 2.5%, in POC, Sim, Prav, Sim-POC, and Prav-POC groups, respectively, vs. 49.3 ± 1.9% in control, P < 0.05), but only Prav did so in Chol animals (25.7 ± 3.3 and 25.3 ± 3.9% in Prav-Chol and Prav-POC-Chol vs. 50.9 ± 1.7, 44.8 ± 4.3, 41.5 ± 3.5, and 49.3 ± 5.5% in Chol, Sim-Chol, POC-Chol, and Sim-POC-Chol, respectively, P < 0.05). L-NAME abolished the infarct size-limiting effect of POC and Prav-Chol. Prav induced the greatest reduction in NT, while it was the only intervention that increased myocardial eNOS and Akt in Chol rabbits (P < 0.05 vs. all others).
  
  
  CONCLUSIONS
  Prav, in contrast to same-dose Sim or POC, reduces infarction in Chol rabbits independently of lipid lowering, potentially through eNOS activation and nitro-oxidative stress attenuation.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Athens School of Pharmacy, Panepistimiopolis, Zografou, Athens 15771, Greece. jandread@pharm.uoa.gr
authors.forename: Ioanna
authors.initials: I
authors.lastname: Andreadou
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Farmakis
authors.forename: Eftihios
authors.initials: E
authors.lastname: Prokovas
authors.forename: Fragiska
authors.initials: F
authors.lastname: Sigala
authors.forename: Anastasia
authors.initials: A
authors.lastname: Zoga
authors.forename: Katerina
authors.initials: K
authors.lastname: Spyridaki
authors.forename: Apostolos
authors.initials: A
authors.lastname: Papalois
authors.forename: Andreas
authors.initials: A
authors.lastname: Papapetropoulos
authors.forename: Maria
authors.initials: M
authors.lastname: Anastasiou-Nana
authors.forename: Dimitrios Th
authors.initials: DT
authors.lastname: Kremastinos
authors.forename: Efstathios K
authors.initials: EK
authors.lastname: Iliodromitis
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D018384:Oxidative Stress; D017035:Pravastatin / Q000494:pharmacology / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011817:Rabbits; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000924:Anticholesteremic Agents; D009569:Nitric Oxide; D019821:Simvastatin; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; D017035:Pravastatin