Patients with hypothyroidism are considered to have an increased risk of developing atherosclerosis. Uncoupling of endothelial nitric oxide synthase from tetrahyrobiopterin, an essential cofactor, leads to the decrease of nitric oxide production and increase in reactive oxygen species. Both mechanisms contribute to atherosclerotic vascular disease. The aim of this study was to investigate whether hypothyroidism influences the systemic redox-state and the structure of aortic vascular endothelium in thyroidectomized rats. Twenty-eight Sprague-Dawley rats were randomly assigned to two groups; sham thyroidectomy and near-total thyroidectomy. Three weeks after surgery, nitric oxide in plasma, homocysteine, cysteine, glutathione levels and superoxide dismutase activity were measured in serum, and biopterine and creatinine were measured in urine. Aortic endothelium samples were processed for light and transmission electron microscopy. Although superoxide dismutase activity remained constant, urine biopterin levels and serum nitric oxide levels decreased in hypothyroid rats compared to their euthyroid controls. Aortic endothelium showed early features of atherosclerosis, and transmission electron microscopy revealed budding of caveolae in endothelial cells. It is concluded that hypothyroidism might lead to systemic oxidative stress with resultant endothelial dysfunction, and subsequent occurrence of atherosclerosis. (C) 2010 Elsevier GmbH. All rights reserved.