INDUCTION OF NITRIC-OXIDE SYNTHASE IN THE NEOINTIMA INDUCED BY A PERIARTERIAL COLLAR IN RABBITS

A Silastic collar placed around the common carotid artery of rabbits c auses the formation, within 7 days, of an atheroma-like neointima cont aining cells with the appearance of synthetic-phenotype smooth muscle cells. Using immunohistochemistry, we detected the appearance of the c ytokine-inducible form of nitric oxide synthase (iNOS, or isoform II) in the neointima of rabbits that had the collar in place for 7 or 14 d ays. This iNOS immunofluorescence collocalized with anti-smooth muscle myosin in the intima, indicating that it is expressed in smooth muscl e cells, and iNOS was also present in a few endothelial cells in colla red sections. There was no evidence of iNOS expression in the arterial wall before the neointima was apparent, that is, after only 2 days wi th the collar. The expression of endothelial NOS (eNOS, or isoform III ) immunofluorescence was confined to the endothelial cells in control sections, as it was in collared sections with neointima at 7 and 14 da ys. Specific immunofluorescence for neuronal NOS (nNOS, or isoform I) was not observed in any sections. Our results suggest that nitric oxid e is produced by the inducible isoform of NOS in modified smooth muscl e cells of the developing neointima. Activity of iNOS might deprive th e endothelium of substrate for nitric oxide production and might expla in the compromised endothelium-dependent vasodilatation observed both in this model of atherosclerosis and in human coronary artery disease.