title: Local infusion of the nitric oxide donor Sin-1 after angioplasty. Effects on intimal hyperplasia in porcine coronary arteries.
abstract: OBJECTIVE
  To investigate the development of intimal hyperplasia in response to percutaneous transluminal coronary angioplasty (PTCA) followed by local delivery of the nitric oxide (NO) donor 3-morpholino-sydnonimine (SIN-1).
  
  
  METHODS
  Overdilation PTCA was performed in coronary arteries in 20 healthy pigs. One of the dilated segments was additionally treated with local delivery of SIN-1 for 10 min. Segments distal to the treated part of the arteries served as controls. Arteries were radiographically depicted and analyzed after 1 and 8 weeks for actin, myosin and intermediate filaments (IF), nitric oxide synthetase (NOS) and histological evaluation.
  
  
  RESULTS
  Segments treated with PTCA+SIN-1 showed a significantly (p=0.03) larger luminal diameter compared with PTCA only treated segments. The luminal loss after SIN-1 was not significant compared with the diameter prior to treatment. Endothelial NOS content was significantly lower in the PTCA+SIN-1 group compared with the PTCA group after 1 (p=0.03) and 8 weeks (p=0.013). IF/actin ratio after 1 week was significantly increased in PTCA-treated segments compared with untreated controls (p=0.004), and compared with PTCA+SIN-1-treated segments (p=0.004).
  
  
  CONCLUSIONS
  PTCA-induced intimal hyperplasia was potently inhibited by local delivery of the NO donor SIN-1. Momentary events at the time of injury play a significant role in the development of intimal hyperplasia and long-lasting down-regulation of the endothelial NOS expression after SIN-1 exposure is suggested. The IF/actin ratio can be useful as an early marker of intimal hyperplasia.
authors.affiliation: Heart Lung Division, Heart Radiology, University Hospital Lund, Lund, Sweden. jan.harnek@skane.se
authors.forename: J
authors.initials: J
authors.lastname: Harnek
authors.forename: E
authors.initials: E
authors.lastname: Zoucas
authors.forename: R
authors.initials: R
authors.lastname: Sjuve
authors.forename: A
authors.initials: A
authors.lastname: Arner
authors.forename: E
authors.initials: E
authors.lastname: Ekblad
authors.forename: H
authors.initials: H
authors.lastname: Schou
authors.forename: V
authors.initials: V
authors.lastname: Perez de Sá
authors.forename: U
authors.initials: U
authors.lastname: Stenram
mesh_terms: D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D023903:Coronary Restenosis / Q000517:prevention & control*; D003331:Coronary Vessels / Q000473:pathology; D005260:Female; D006965:Hyperplasia; D008297:Male; D008981:Molsidomine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000008:administration & dosage* / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013552:Swine; D017539:Tunica Intima / Q000473:pathology*
chemical_list: D020030:Nitric Oxide Donors; C002385:linsidomine; D008981:Molsidomine; D019001:Nitric Oxide Synthase; D000254:Sodium-Potassium-Exchanging ATPase