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TJ0711, a novel vasodilatory β-blocker, protects SHR rats against hypertension induced renal injury

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单位: [1]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Nephrol, Wuhan 430030, Peoples R China [2]Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Pharm, Wuhan 430030, Peoples R China [3]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Ctr Biomed Res, Wuhan 430030, Peoples R China [4]Georgia Regents Univ, Med Coll Georgia, Ctr Biotechnol & Genom Med, Augusta, GA 30912 USA
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关键词: TJ0711 carvedilol hypertension renal injury renoprotection

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Previous studies suggested that beta-blockers with adjunctive alpha(1)-blocking activities warrant renoprotective function other than the therapeutic effect on hypertension. The current report is designed to dissect the role of TJ0711, a novel beta-blocker with a 1:1 ratio for the beta(1)/alpha(1) blocking activities, in renoprotection in SHR rats. It was noted that TJ0711 possesses similar potency for control of blood pressure as that of Carvedilol. However, TJ0711 is much more potent in terms of protecting SHR rats against hypertension induced renal injury. Specifically, SHR rats treated with 20mg/kg/day of TJ0711 manifested significantly lower levels for urine albumin and total protein. In line with these result, TJ0711 treated rats displayed much less severe pathological changes in the kidneys. Mechanistic studies revealed that TJ0711 improves kidney perfusion during the course of hypertensive insult by enhancing eNOS expression through suppressing inflammatory cytokine secretion. TJ0711 also attenuates Vasohibin-1 expression to prevent HIF-1 alpha from signal-induced degradation, and by which it promotes HO-1 expression to protect SHR rats against oxidative stress induced by hypertension in the kidneys. Together, our data suggest that TJ0711 possesses higher potency for renoprotection while manifesting the similar effect on hypertension therapy as Carvedilol.

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大类 | 4 区 医学
小类 | 4 区 医学:研究与实验 4 区 肿瘤学
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出版当年[2011]版:
最新[2024]版:
Q3 MEDICINE, RESEARCH & EXPERIMENTAL Q4 ONCOLOGY

影响因子: 最新[2024版] 最新五年平均 出版当年[2011版] 出版当年五年平均 出版前一年[2010版]

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第一作者单位: [1]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Nephrol, Wuhan 430030, Peoples R China
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通讯机构: [1]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Nephrol, Wuhan 430030, Peoples R China [*1]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Internal Med,Div Nephrol, Wuhan 430030, Peoples R China
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