Preventive but nontherapeutic effect of danshensu on hypoxic pulmonary hypertension

OBJECTIVES: Danshensu is a traditional Chinese medicine that is used for treatment of cardiovascular diseases. We previously demonstrated its preventive effect against early-stage hypoxic pulmonary hypertension (HPH) in a rat model. To determine whether danshensu treatment might be useful for patients with chronic HPH, we examined its therapeutic effect in rats with prolonged HPH. METHODS: Adult Sprague-Dawley rats received danshensu (80, 160, and 320 mg/kg) during or after hypoxia exposure to assess preventive and therapeutic effects, respectively. Right ventricle systolic pressure (RVSP), right ventricle hypertrophy index (RVHI), and mean left carotid artery pressure (mCAP) were measured in each group. Western blotting was used to assess transforming growth factor (TGF)-β expression levels in rats and cultured cells exposed to hypoxia. RESULTS: Preventive danshensu treatment significantly reduced the elevation of RVSP and RVHI in rats exposed to hypoxia, whereas therapeutic danshensu treatment did not; mCAP did not change in any treatment group. The increased expression levels of TGF-β induced by hypoxia were inhibited by preventive danshensu treatment, but not by therapeutic danshensu treatment. CONCLUSIONS: Although danshensu treatment could prevent HPH, it had no obvious therapeutic effect after development of HPH. Therefore, danshensu might be suitable for clinical treatment of early-stage HPH.