Local infusion of the nitric oxide donor Sin-1 after angioplasty. Effects on intimal hyperplasia in porcine coronary arteries.
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.
Harnek
J
J
Heart Lung Division, Heart Radiology, University Hospital Lund, Lund, Sweden. jan.harnek@skane.se
Zoucas
E
E
Sjuve
R
R
Arner
A
A
Ekblad
E
E
Schou
H
H
Perez de Sá
V
V
Stenram
U
U
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*
D020030:Nitric Oxide Donors; C002385:linsidomine; D008981:Molsidomine; D019001:Nitric Oxide Synthase; D000254:Sodium-Potassium-Exchanging ATPase