Preventive effect of tetramethylpyrazine on nitroglycerin-tolerance in rats by improving oxidative stress and ribosome homeostasis

Nitroglycerin (NTG) is recommended as the first-line drug in angina pectoris though its prolonged use impacts nitroglycerin tolerance. In this study, we investigated the preventive effect of Tetramethylpyrazine (TMP), a famous Chinese medicine used for cardiovascular diseases, on NTG-induced tolerance and further explained the underlying mechanism of its action. The results revealed that pretreatment of TMP improved NTG-induced tolerance in vitro thoracic aorta rings and in rats. Proteomic analysis showed oxidative stress and ribosome proteins dyshomeostasis in NTG-tolerance vessels. TMP attenuated the oxidative stress by enhancing the protein expression of ALDH2, Nrf2 and HO-1. In addition, TMP recovered the down-regulated expression of RpL10a induced by nitroglycerin. Therefore, TMP could prevent nitroglycerin tolerance in rats, which may be mediated by up-regulation of ALDH2 and Nrf2/HO-1 signaling pathway and involved in the restoration of ribosome homeostasis. These findings indicate the potential of TMP as a promising medicine for preventing the development of nitroglycerin-induced tolerance.