Atherosclerotic lesions are associated with increased immunoreactivity for inducible nitric oxide synthase and endothelin-1 in thoracic aortic intimal cells of hyperlipidemic Watanabe rabbits

The development and progression of atherosclerotic lesions in Watanabe heritable hyperlipidemic rabbits is associated with increases in inducible nitric oxide synthase (NOS2) and endothelin-1 (ET-1) immunoreactivity. In contrast, there is a reduction of immunoreactivity for neuronal NOS (NOS 1) in aortic endothelial cells. but no change in endothelial NOS (NOS3) immunoreactivity. However. subendothelial macrophages and smooth muscle showed a different pattern of immunoreactivity of NADPH-diaphorase (NADPH-d), NOS2, ET-1. and NOS 1. The lipid-rich macrophages in the intima were positively labeled for NADPH-d, NOS1 NOS2, NOS3, and ET-1. Smooth muscle cells in the subendothelium and the medial layers of the vascular wall were also positive for these markers. These results are consistent with the reduction of endothelium-dependent vasorelaxation that is known to occur during the development and progression of atherosclerosis in familial hypercholesterolemia. The data suggest a key role for vasoactive substances in the development of atherosclerosis. (C) 2001 Academic Press.