title: The antiadhesive and antithrombotic effects of the nitric oxide donor SIN-1 are combined with a decreased vasoconstriction in a porcine model of balloon angioplasty.
abstract: Nitric oxide has been reported to modulate platelet and neutrophil interactions with the arterial wall. In this study, we investigated the effects of the nitric oxide donor 3-morpholino-sydnonimine (SIN-1) on platelet and neutrophil adhesion, and the vasomotor response, in a porcine model of angioplasty. Carotid arterial injury was produced by balloon dilation in control (n = 10) and treated (SIN-1; 10 micrograms/kg + 1 microgram/kg/min, i.v.) (n = 8) pigs. At the site of deep arterial injury, the average platelet adhesion was 53.6 +/- 11.3 x 10(6)/cm2 in the control animals and was significantly inhibited by more than 70%, to 15.1 +/- 4.1 x 10(6)/cm2 (P < .01), by SIN-1. Neutrophil adhesion was also decreased by SIN-1, from 255.9 +/- 29.7 to 101.8 +/- 19.7 x 10(3)cm2 (P < .001). Mural thrombosis was found in 12 (71%) of the 17 injured arteries in the control group but in only 2 (17%) of the 12 injured arteries in the SIN-1-treated group (P < .05). Concomitantly, SIN-1 reduced platelet and neutrophil adhesion to the site of endothelial injury distally. The internal diameter of the carotid arteries was similar between the two groups before dilation but was 40% greater at the site of endothelial injury distally in SIN-1-treated animals after dilation (P < .05), as compared with controls. Accordingly, postangioplasty vasoconstriction was significantly attenuated from 46.3 +/- 2.9% in control pigs to 32.5 +/- 4.8% (P < .05) in SIN-1-treated animals. The beneficial effects of SIN-1 were associated with inhibition of neutrophil-mediated whole blood aggregation and of neutrophil-endothelium interactions. The potent antiadhesive and antithrombotic properties of SIN-1 in vivo were confirmed in ex vivo superfusion experiments. These results indicate that administration of a nitric oxide donor may be effective in preventing the acute pathophysiological responses to arterial injury by angioplasty.
authors.affiliation: Laboratory of Experimental Pathology, Hôtel-Dieu de Montréal, Quebec, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Provost
authors.forename: J
authors.initials: J
authors.lastname: Tremblay
authors.forename: Y
authors.initials: Y
authors.lastname: Merhi
mesh_terms: D000800:Angioplasty, Balloon; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects; D020212:Carotid Artery Injuries; D002448:Cell Adhesion / Q000187:drug effects; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D010477:Perfusion; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D014665:Vasodilator Agents; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine