3-4-dihydroxyphenyllactic-acid and Hypertension--Pulmonary

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.. 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.. 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.. 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.

Topics: Animals; Blood Pressure; Carotid Arteries; Cells, Cultured; Disease Models, Animal; Drugs, Chinese Herbal; Female; Fibroblasts; Heart Ventricles; Humans; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Hypoxia; Lactates; Male; Primary Cell Culture; Pulmonary Artery; Rats; Rats, Sprague-Dawley; Time Factors; Time-to-Treatment

Hypoxic pulmonary hypertension is characterized by the remodeling of pulmonary artery. Previously we showed that tanshinone IIA, one lipid-soluble component from the Chinese herb Danshen, ameliorated hypoxic pulmonary hypertension by inhibiting pulmonary artery remodeling. Here we explored the effects of danshensu, one water-soluble component of Danshen, on hypoxic pulmonary hypertension and its mechanism. Rats were exposed to hypobaric hypoxia for 4 weeks to develop hypoxic pulmonary hypertension along with administration of danshensu. Hemodynamics and pulmonary arterial remodeling index were measured. The effects of danshensu on the proliferation of primary pulmonary artery smooth muscle cells and transforming growth factor-β-smad3 pathway were assessed in vitro. Danshensu significantly decreased the right ventricle systolic pressure, the right ventricle hypertrophy and pulmonary vascular remodeling index in hypoxic pulmonary hypertension rats. Danshensu also reduced the increased expression of transforming growth factor-β and phosphorylation of smad3 in pulmonary arteries in hypoxic pulmonary hypertension rats. In vitro, danshensu inhibited the hypoxia- or transforming growth factor-β-induced proliferation of primary pulmonary artery smooth muscle cells. Moreover, danshensu decreased the hypoxia-induced expression and secretion of transforming growth factor in primary pulmonary adventitial fibroblasts and NR8383 cell line, inhibited the hypoxia or transforming growth factor-β-induced phosphorylation of smad3 in rat primary pulmonary artery smooth muscle cells. These results demonstrate that danshensu ameliorates hypoxic pulmonary hypertension in rats by inhibiting the hypoxia-induced proliferation of pulmonary artery smooth muscle cells, and the inhibition effects is associated with transforming growth factor-β-smad3 pathway. Therefore danshensu may be a potential treatment for hypoxic pulmonary hypertension.

Topics: Animals; Cell Hypoxia; Cell Line; Cell Proliferation; Fibroblasts; Hypertension, Pulmonary; Lactates; Male; Myocytes, Smooth Muscle; Phosphorylation; Pulmonary Artery; Rats; Rats, Sprague-Dawley; Signal Transduction; Smad3 Protein; Transforming Growth Factor beta