{
    "abstract": "Myocardial fibrosis (MF) is an unavoidable complication in patients with hypertensive heart disease. Valsartan, a widely used antihypertensive drug, was reported to inhibit MF. Deficiency in the 5-hydroxytryptamine (5-HT, serotonin) transporter gene has been proven to cause MF. Long-term sympathetic nerve excitability activates renin angiotensin aldosterone system leading to MF. Tandospirone, a partial agonist of the 5-HT1A receptor, has been commonly used to relieve psychiatric symptoms. However, there is limited evidence on the combination of valsartan and tandospirone for the treatment of MF. Therefore, we investigated the synergistic effect of tandospirone on the anti-MF activity of valsartan in spontaneously hypertensive rats (SHRs).\nSystolic blood pressure (SBP) of SHRs (12-week-old) was measured weekly using the tail-cuff method for eight weeks; the left ventricular was collected and weighted for calculation of the left ventricular mass index (LVMI). The myocardial histopathology of left ventricle was evaluated in rats by hematoxylin and eosin (H&E) and Mason's trichrome staining assays. The mRNA and protein expressions of transforming growth factor \u03b2 (TGF-\u03b21), Sma- and Mad-related protein 3 (Smad3), and fibronectin (Fn) were investigated by real time PCR, immunohistochemistry, and Western blotting analysis, respectively.\nTandospirone (40 mg/kg) could significantly improve the effect of valsartan (30 mg/kg) in decreasing the SBP of SHRs and lower the ratio of the LVMI in SHRs, compared to that of rats treated with valsartan or tandospirone alone. Tandospirone could also enhance the valsartan-induced reduction in collagen deposition in the myocardial tissues of SHRs. Furthermore, tandospirone could enhance the effect of valsartan on downregulating the expression levels of TGF-\u03b21, Smad3, and Fn at both mRNA and protein levels.\nWe report for the first time that tandospirone could improve the anti-MF efficacy of valsartan via the TGF-\u03b21/Smad3 signaling pathway in SHRs. Our findings may provide valuable insight into the scientific rationale for combining tandospirone and valsartan in the treatment of MF clinically.",
    "authors": [
        {
            "affiliation": "School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, China.",
            "firstname": "Xuefei",
            "initials": "X",
            "lastname": "Huang"
        },
        {
            "affiliation": "School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, China.",
            "firstname": "Yaqi",
            "initials": "Y",
            "lastname": "Kang"
        },
        {
            "affiliation": "School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, China.",
            "firstname": "Xinrui",
            "initials": "X",
            "lastname": "Jiang"
        },
        {
            "affiliation": "School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, China; Institute of Cardiovascular Research, The Key Laboratory of Medical Electrophysiology, Ministry of Education of China, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province, Medical Key Laboratory for Drug Discovery and Druggability Evaluation of Sichuan Province, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, Luzhou, 646000, China.",
            "firstname": "Jing",
            "initials": "J",
            "lastname": "Yang"
        },
        {
            "affiliation": "School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, China; Institute of Cardiovascular Research, The Key Laboratory of Medical Electrophysiology, Ministry of Education of China, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province, Medical Key Laboratory for Drug Discovery and Druggability Evaluation of Sichuan Province, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, Luzhou, 646000, China.",
            "firstname": "An-Guo",
            "initials": "AG",
            "lastname": "Wu"
        },
        {
            "affiliation": "Sichuan CREDIT Pharmaceutical Ltd., Luzhou, Sichuan, 646000, China.",
            "firstname": "Chuanqing",
            "initials": "C",
            "lastname": "Zhang"
        },
        {
            "affiliation": "School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, China; Institute of Cardiovascular Research, The Key Laboratory of Medical Electrophysiology, Ministry of Education of China, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province, Medical Key Laboratory for Drug Discovery and Druggability Evaluation of Sichuan Province, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, Luzhou, 646000, China.",
            "firstname": "Dalian",
            "initials": "D",
            "lastname": "Qin"
        },
        {
            "affiliation": "School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, China.",
            "firstname": "Shousong",
            "initials": "S",
            "lastname": "Cao"
        },
        {
            "affiliation": "School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, China.",
            "firstname": "Qibin",
            "initials": "Q",
            "lastname": "Mei"
        },
        {
            "affiliation": "School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, China; Department of Pharmacy, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China. Electronic address: yeyun8622@163.com.",
            "firstname": "Yun",
            "initials": "Y",
            "lastname": "Ye"
        },
        {
            "affiliation": "School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, China; Institute of Cardiovascular Research, The Key Laboratory of Medical Electrophysiology, Ministry of Education of China, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province, Medical Key Laboratory for Drug Discovery and Druggability Evaluation of Sichuan Province, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, Luzhou, 646000, China; Department of Pharmacy, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China. Electronic address: jianmingwu@swmu.edu.cn.",
            "firstname": "Jianming",
            "initials": "J",
            "lastname": "Wu"
        }
    ],
    "conclusions": "We report for the first time that tandospirone could improve the anti-MF efficacy of valsartan via the TGF-\u03b21/Smad3 signaling pathway in SHRs. Our findings may provide valuable insight into the scientific rationale for combining tandospirone and valsartan in the treatment of MF clinically.",
    "copyrights": "Copyright \u00a9 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.",
    "doi": "10.1016/j.biopha.2020.110073",
    "journal": "Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie",
    "keywords": [
        "Hypertension",
        "Myocardial fibrosis",
        "TGF-\u03b21/Smad3",
        "Tandospirone",
        "Valsartan"
    ],
    "methods": null,
    "publication_date": "2020-03-18",
    "pubmed_id": "32179201",
    "results": "Tandospirone (40 mg/kg) could significantly improve the effect of valsartan (30 mg/kg) in decreasing the SBP of SHRs and lower the ratio of the LVMI in SHRs, compared to that of rats treated with valsartan or tandospirone alone. Tandospirone could also enhance the valsartan-induced reduction in collagen deposition in the myocardial tissues of SHRs. Furthermore, tandospirone could enhance the effect of valsartan on downregulating the expression levels of TGF-\u03b21, Smad3, and Fn at both mRNA and protein levels.",
    "title": "Tandospirone enhances the anti-myocardial fibrosis effect of valsartan in spontaneously hypertensive rats.",
    "xml": "<Element 'PubmedArticle' at 0x788503e2f4c0>"
}