GTN (A, B), ACh (C) and DEA/NO (D) concentration-response curves of aortic rings from untreated WT (open squares), nitrate-tolerant WT (filled squares), ascorbate-supplemented (open circles), ascorbate-deficient (open diamonds) and bortezomib-treated ascorbate-deficient (filled diamonds) Gulo(-/-) mice. For clarity, the high-affinity pathway of the GTN curve is illustrated separately in panel B. Rings were precontracted with the thromboxane mimetic U-46619. In panels A, B and D, data are mean values ± SEM of nine (untreated WT, ascorbate-supplemented, ascorbate-deficient) or five (WT, nitrate-tolerant, bortezomib-treated ascorbate-deficient) animals. In panel C, data are mean values ± SEM of five animals. Concentration-response curves of different ring segments from a single animal were averaged and counted as individual experiment. *P < 0.05 versus ascorbate-deficient animals. The effect of nitrate tolerance is not indicated for reasons of clarity. NS, non-significant.