THE ANTIADHESIVE AND ANTITHROMBOTIC EFFECTS OF THE NITRIC-OXIDE DONORSIN-1 ARE COMBINED WITH A DECREASED VASOCONSTRICTION IN A PORCINE MODEL OF BALLOON ANGIOPLASTY

Nitric oxide has been reported to modulate platelet and neutrophil int eractions with the arterial wall. In this study, we investigated the e ffects of the nitric oxide donor 3-morpholino-sydnonimine (SIN-1) on p latelet and neutrophil adhesion, and the vasomotor response, in a porc ine model of angioplasty. Carotid arterial injury was produced by ball oon dilation in control (n=10) and treated (SIN-1; 10 mu g/kg + 1 mu g /kg/min, IV) (n=8) pigs. At the site of deep arterial injury, the aver age platelet adhesion was 53.6+/-11.3x10(6)/cm(2) in the control anima ls and was significantly inhibited by more than 70%, to 15.1+/-4.1x10( 6)/cm(2) (P<.01), by SIN-1. Neutrophil adhesion was also decreased by SIN-1, from 255+/-29.7 to 101.8+/-19.7x10(3)/cm(2) (P<.001). Mural thr ombosis was found in 12 (71%) of the 17 injured arteries in the contro l group but in only 2 (17%) of the 12 injured arteries in the SIN-1-tr eated group (P<.05). Concomitantly, SIN-1 reduced platelet and neutrop hil adhesion to the site of endothelial injury distally. The internal diameter of the carotid arteries was similar between the two groups be fore dilation but was 40% greater at the site of endothelial injury di stally in SIN-1-treated animals after dilation (P<.05), as compared wi th controls. Accordingly, postangioplasty vasoconstriction was signifi cantly 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 ass ociated with inhibition of neutrophil-mediated whole blood aggregation and of neutrophil-endothelium interactions. The potent antiadhesive a nd antithrombotic properties of SIN-1 in vivo were confirmed in ex viv o superfusion experiments. These results indicate that administration of a nitric oxide donor may be effective in preventing the acute patho physiological responses to arterial injury by angioplasty.