title: Endogenous and exogenous nitric oxide protect against intracoronary thrombosis and reocclusion after thrombolysis.
abstract: BACKGROUND
  Nitric oxide (NO), an endothelium-derived relaxing factor, plays an important role in regulating platelet activation. We evaluated the effect of NO in a canine model of intracoronary thrombosis, thrombolysis, and reocclusion.
  
  
  RESULTS
  Before thrombosis was induced, 34 anesthetized dogs were treated with a continuous intracoronary infusion of saline (n = 8); NG-nitro-L-arginine (L-NNA, n = 8), an inhibitor of NO synthetase; L-arginine (n = 7), the precursor for NO; or sodium nitroprusside (SNP, n = 11), an NO donor. Ten minutes after the infusion was begun, an electric current of 150 microA was applied to the endothelium of coronary arteries to induce thrombosis. Occlusive thrombi developed in all dogs in the saline group (38 +/- 4 minutes) and the L-NNA group (30 +/- 6 minutes), in 6 of 7 dogs in the L-arginine group (81 +/- 18 minutes), and in 6 of 11 dogs in the SNP group (102 +/- 21 minutes) (P < .01). The time to thrombus was prolonged by L-arginine (P < .05) and SNP (P < .01). After 3 hours of thrombus formation in coronary arteries, tissue plasminogen activator and heparin were administered intravenously. Thrombi were lysed in 4 (of 8) dogs in the saline group (71 +/- 8 minutes), in 4 (of 8) dogs in the L-NNA group (72 +/- 8 minutes), in 4 (of 6) dogs in the L-arginine group (50 +/- 14 minutes), and in 4 (of 6) dogs in the SNP group (49 +/- 11 minutes) (P > .05). After thrombolysis, coronary artery reocclusion developed in all reperfused dogs in the saline group (30 +/- 8 minutes) and in the L-NNA group (48 +/- 12 minutes), in 3 (of 4) reperfused dogs in the L-arginine group (123 +/- 26 minutes), and in 3 (of 4) reperfused dogs in the SNP group (128 +/- 19 minutes) (P < .01). The ex vivo platelet aggregation induced by collagen was inhibited after in vivo treatment with L-arginine or SNP.
  
  
  CONCLUSIONS
  Increasing NO production or giving an NO donor may inhibit platelet aggregation and delay intracoronary thrombus formation and reocclusion after thrombolysis.
authors.affiliation: Cullen Cardiovascular Research Laboratory, Texas Heart Institute, Houston, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Yao
authors.forename: S
authors.initials: S
authors.lastname: Akhtar
authors.forename: T
authors.initials: T
authors.lastname: Scott-Burden
authors.forename: J C
authors.initials: JC
authors.lastname: Ober
authors.forename: P
authors.initials: P
authors.lastname: Golino
authors.forename: L M
authors.initials: LM
authors.lastname: Buja
authors.forename: W
authors.initials: W
authors.lastname: Casscells
authors.forename: J T
authors.initials: JT
authors.lastname: Willerson
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003326:Coronary Circulation; D003328:Coronary Thrombosis / Q000097:blood / Q000517:prevention & control / Q000628:therapy*; D004285:Dogs; D004558:Electric Stimulation; D006400:Hematocrit; D009569:Nitric Oxide / Q000494:pharmacology* / Q000502:physiology*; D009573:Nitrites / Q000097:blood; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D012008:Recurrence; D015912:Thrombolytic Therapy; D014914:Whole Blood Coagulation Time
chemical_list: D009573:Nitrites; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine