S-Nitroso-N-acetylpenicillamine is a Potent Inhibitor of Neutrophil-Endothelial Interaction

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Abstract
Inhibition of polymorphonuclear (PMN) leukocytes' adherence to the endothelium and their consequent activation represents a novel approach to the treatment of those diseases in which PMNs play an important role. In this study, we observed the effects of S-nitroso-N-acetylpenicillamine (SNAP), a nitrosothiol nitric oxide (NO) donor, on cat PMN adherence to autologous coronary vascular endothelium and activated PMN-induced vasocontraction with accompanying endothelial dysfunction. SNAP, at concentrations between 2.5 nM to 250 nM, dilated cat coronary artery rings in a concentration-dependent manner with peak vasodilator responses occurring at 50 nM. Addition of 1 nM SNAP, a concentration at which no significant vasorelaxation occurred, significantly inhibited leukotriene B4 (LTB4 activated PMN adherence to normal endothelium (p < 0.05). Inhibition of endothelial NO formation by N -nitro-L-arginine methyl ester induced a two- to three-fold increase of PMN adherence to the endothelium, which was almost completely prevented by 1 nM-SNAP (p < 0.001). Moreover, addition of InM-SNAP also significantly decreased LTB4 activated PMN-induced vasocontraction and prevented endothelial dysfunction. These results indicate that SNAP has significant anti-PMN effects, and may have particular utility in preventing tissue injury associated with myocardial ischemia and reperfusion.