title: Fluvastatin reduces pulmonary vein spontaneous activity through nitric oxide pathway.
abstract: BACKGROUND
  Pulmonary veins (PVs) are the most important focus for the generation of atrial fibrillation. The HMG-CoA reductase inhibitors (statins) can reduce the occurrence of atrial fibrillation. The purposes of this study were to evaluate whether statins may inhibit the PV arrhythmogenic activity to prevent atrial arrhythmias from PVs and to investigate the link between fluvastatin, nitric oxide synthase (NOS) activity, mechanical activity, and electrical activity.
  
  
  METHODS
  Conventional microelectrodes and Western blot were used to record the electrical activity, diastolic tension, contractility and expression of Akt, endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), and phosphorylated Akt and eNOS before and after the administration of fluvastatin in rabbit PVs or atria.
  
  
  RESULTS
  Fluvastatin decreased the PV spontaneous activity, diastolic tension, and contractility, but did not change the action potential duration or resting membrane potential. The effects of fluvastatin on the PV firing rate and diastolic tension were attenuated in the presence of L-NAME (100 microM), wortmannin (100 nM), and ODQ (3 microM). Fluvastatin (1 muM) increased the phosphorylated Akt and eNOS, but did not change the total Akt or eNOS in the PVs and atria. In contrast, fluvastatin (1 microM) decreased the total nNOS in the PVs and atria.
  
  
  CONCLUSIONS
  Fluvastatin produced nitric oxide through the PI3kinase/Akt pathway, thus reducing the PV vascular diastolic tension and PV spontaneous activity. These results may contribute to the beneficial effects of statins.
authors.affiliation: Division of Cardiology and Cardiovascular Research Center, Veterans General Hospital-Taipei, Taiwan.
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Hu
authors.forename: Yao-Chang
authors.initials: YC
authors.lastname: Chen
authors.forename: Chen-Chuan
authors.initials: CC
authors.lastname: Cheng
authors.forename: Satoshi
authors.initials: S
authors.lastname: Higa
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Chen
authors.forename: Shih-Ann
authors.initials: SA
authors.lastname: Chen
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001281:Atrial Fibrillation / Q000503:physiopathology; D015153:Blotting, Western; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use*; D000077340:Fluvastatin; D006325:Heart Atria / Q000187:drug effects; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D066298:In Vitro Techniques; D007211:Indoles / Q000627:therapeutic use*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051058:Oncogene Protein v-akt / Q000502:physiology; D010069:Oxadiazoles / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011667:Pulmonary Veins / Q000187:drug effects*; D011810:Quinoxalines / Q000494:pharmacology; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000077191:Wortmannin
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D000730:Androstadienes; D004791:Enzyme Inhibitors; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D010069:Oxadiazoles; D011810:Quinoxalines; D009569:Nitric Oxide; D000077340:Fluvastatin; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; D019331:NG-Nitroarginine Methyl Ester; D000077191:Wortmannin