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Am J Transl Res 2013;5(3):279-290

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

Juan Yang, Yong Ning, Jun Qiu, Jin-Seng He, Wei Li, Zu-Fu Ma, Ju-Fang Shao, Yue-Qiang LI, Rui Zeng, Meng
Zhang, Jia Cheng, Su-Fang Chen, Gang Xu, Cong-Yi Wang, Ying Yao

Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and
Technology, Wuhan 430030, China; Department of Pharmacy, Tongji Medical College, Huazhong University of
Science and Technology, Wuhan 430030, China; The Center for Biomedical Research, Tongji Hospital, Tongji
Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; The Center for
Biotechnology and Genomic Medicine, Medical College of Georgia, Georgia Regents University, 1120 15th Street,
CA4098, Augusta, GA 30912, USA. These authors contributed equally to this work.

Received February 1, 2013; Accepted March 21, 2013; Epub April 19, 2013; Published April 30, 2013

Abstract: Previous studies suggested that β-blockers with adjunctive α1-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 β-blocker with a 1:1 ratio for the β1/α1 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-1α 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. (AJTR1302001).

Keywords: TJ0711, carvedilol, hypertension, renal injury, renoprotection

Address correspondence to: Dr. Ying Yao, Division of Nephrology, Department of Internal Medicine, Tongji
Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. E-
mail: yaoyingkk@126.com; Dr. Cong-Yi Wang, The Center for Biotechnology and Genomic Medicine, Medical
College of Georgia, Georgia Regents University, 1120 15th Street, CA4098, Augusta, GA 30912, USA. E-mail:
cwang@gru.edu