Background—Although endothelial nitric oxide synthase (NOS) is antiatherogenic, the role of inducible NOS (iNOS) in the development of atherosclerosis is not established.

Methods and Results—We compared the susceptibility of iNOS knockout (iNOS^−/−) and wild-type (iNOS^+/+) mice to the development of atherosclerosis induced by feeding an atherogenic diet for 15 weeks. Plasma lipid level, atherosclerotic lesion size, and cellular density in the lesions were all similar in the 2 strains (lesion size: iNOS^+/+ 285±73×10³ μm², iNOS^−/− 293±82×10³ μm², n=10). iNOS mRNA was detected in the lesions of iNOS^+/+ but not iNOS^−/− mice through RT-PCR. Immunohistochemically, iNOS^+/+ mice showed iNOS staining in macrophages and medial smooth muscle cells in the lesions. Nitrotyrosine staining showed a similar distribution, whereas it was absent in iNOS^−/− mice. There was no apparent difference in the intensity or distribution of vascular cell adhesion molecule-1 staining in the lesions of the 2 strains. However, the lesions of iNOS^+/+ mice showed a markedly decreased extracellular collagen content compared with those of iNOS^−/− mice

Conclusions—iNOS induction does not affect the development of atherosclerosis in mice fed an atherogenic diet, but the resulting lesions show decreased levels of extracellular collagen and may be more fragile.