Effects of Tetramethylpyrazine, a Chinese Medicine, on Plasma Endothelin-1 Levels During Acute Pulmonary Hypoxia in Anesthetized Dogs

Our study was designed to elucidate the effects of tetramethylpyrazine (TMP), a Chinese medicine, on plasma endothelin-1 (ET-1) levels in dogs with acute pulmonary alveolar hypoxia. Anesthetized dogs were used under artificial ventilation with room air or a hypoxic gas mixture (10% O2 and 90% N2) (n = 10) for 60 min. Effects of TMP (80 mg/kg) were studied by i.v. injection of TMP before exposure to hypoxia (n = 8). Mean pulmonary arterial pressure (PAPm), systemic arterial pressure (SAPm), right atrial pressure (RAP), pulmonary capillary wedge pressure (PCWP), cardiac output (CO), and heart rate (HR) were measured. The pulmonary vascular resistance (PVR) was calculated by the equation of (PAPm-PCWP) x 8/CO. Plasma ET-1 levels were determined in the abdominal aorta and pulmonary artery by RIA. The effects of TMP on PAP and plasma ET-1 level were evaluated by using percent increase in PAPm and the change of Da-pET (delta ET) before and after hypoxia. Both PAPm and PVR were significantly elevated 5 min after acute hypoxia over a period of 60 min, whereas CO and PCWP did not change. Plasma ET-1 levels in the abdominal aorta and Da-pET showed a significant increase. Administration of TMP significantly decreased the hypoxia-induced increase in the PAPm, PVR, and delta ET. These results suggest that TMP could be a useful therapeutic agent in the treatment of pulmonary hypertension induced by acute hypoxia through decrease of plasma ET-1 levels.