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TMP has a long history of beneficial effects in the treatment of many cardiovascular diseases. Here we have evaluated the therapeutic effects of TMP on pulmonary hypertension (PH) in animal models and in patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH).<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Three well\u2010defined models of PH \u2010chronic hypoxia (10% O<jats:sub>2<\/jats:sub>)\u2010induced PH (HPH), monocrotaline\u2010induced PH (MCT\u2010PH) and Sugen 5416\/hypoxia\u2010induced PH (SuHx\u2010PH) \u2010 were used in Sprague\u2010Dawley rats, and assessed by echocardiography, along with haemodynamic and histological techniques. Primary cultures of rat distal pulmonary arterial smooth muscle cells (PASMCs) were used to study intracellular calcium levels. Western blots and RT\u2010qPCR assays were also used. In the clinical cohort, patients with PAH or CTEPH were recruited. The effects of TMP were evaluated in all systems.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>TMP (100 mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>) prevented rats from developing experimental PH and ameliorated three models of established PH: HPH, MCT\u2010PH and SuHx\u2010PH. The therapeutic effects of TMP were accompanied by inhibition of intracellular calcium homeostasis in PASMCs. In a small cohort of patients with PAH or CTEPH, oral administration of TMP (100 mg, t.i.d. for 16 weeks) increased the 6\u2010min walk distance and improved the 1\u2010min heart rate recovery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Our results suggest that TMP is a novel and inexpensive medication for treatment of PH. Clinical trial is registered with <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"about:blank\">www.chictr.org.cn<\/jats:ext-link> (ChiCTR\u2010IPR\u201014005379).<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15000","type":"journal-article","created":{"date-parts":[[2020,1,24]],"date-time":"2020-01-24T12:44:04Z","timestamp":1579869844000},"page":"2743-2764","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Tetramethylpyrazine: A promising drug for the treatment of pulmonary hypertension"],"prefix":"10.1111","volume":"177","author":[{"given":"Yuqin","family":"Chen","sequence":"first","affiliation":[{"name":"State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University  Guangzhou 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