1. The aims of the present study were to explore the protective effect of curcumin against the acute vascular endothelial dysfunction induced by high glucose and to investigate the possible role of heme oxygenase (HO)-1 in this protective action. 2. Thoracic aortic rings, with or without endothelium, obtained from male Sprague-Dawley rats were mounted in an organ bath. Isometric contraction of the rings was recorded. After completion of the organ bath studies, rings were homogenized and centrifuged (30,000 g, 4 degrees C, 15 min) and HO activity was determined in the supernatant. 3. After 2 h incubation of aortic rings in the presence of high glucose (44 mmol/L), the relaxation evoked by acetylcholine (3 x 10(-8) to 3 x 10(-5) mol/L) was significantly decreased only in rings with an intact endothelium. When rings were coincubated in the presence of curcumin (10(-13) to 10(-11) mol/L) and high glucose, curcumin reversed the vasodilator dysfunction induced by high glucose dose dependently. 4. Curcumin (10(-11) mol/L) increased HO activity in the aortic rings compared with activity in control rings (63.1 +/- 3.6 vs control 43.2 +/- 2.9 pmol/mg per h, respectively; P < 0.01). Protoporphyrin IX zinc (10(-6) mol/L), an inhibitor of HO-1, offset the protective effects of curcumin. In addition, the non-selective guanylate cyclase (GC) inhibitor methylene blue (10(-6) mol/L) completely abolished the protective effects of curcumin. 5. In conclusion, the results of the present study show that curcumin alleviates the acute endothelium-dependent vasodilator dysfunction induced by high glucose in rat aortic rings. Increased HO-1 activity and stimulation of GC may be involved in the protective effects of curcumin.