Nebivolol is a novel β-adrenergic receptor (β-AR) blocker with anti-inflammatory and antioxidant properties. The NLRP3 inflammasome plays a pivotal role in the pathogenesis of obesity-induced vascular dysfunction. Our study aimed to explore the effect of nebivolol on the NLRP3 inflammasome and vascular remodeling in diet-induced obese rats. Eight-week-old Sprague–Dawley male rats were fed with either a standard chow diet or a high-fat diet (HFD) for 8 weeks. Next, the obese rats were subdivided into 3 groups as follows: (1) HFD control group, (2) HFD with low doses of nebivolol (5 mg/kg·d−1), and (3) HFD with high doses of nebivolol (10 mg/kg·d−1). A 4-week treatment with nebivolol improved acetylcholine-induced vascular relaxation in accordance with an increased aortic endothelial nitric oxide synthase. Nebivolol attenuated NLRP3 inflammasome activation and suppressed autophagy. In parallel, nebivolol enhanced the levels of phase-II detoxifying enzymes, including superoxide dismutase and catalase. These effects were associated with an increased β3-AR level. Moreover, nebivolol treatment significantly increased Adenosine 5′-monophosphate (AMP)-activated protein kinase activity and decreased phosphorylation of the mammalian target of rapamycin. These results demonstrated that nebivolol improves obesity-induced vascular remodeling by attenuating NLRP3 inflammasome activation and restoring the antioxidant defense.
*State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China; and
†Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Reprints: Weili Shen, MD, PhD, Department of Hypertension, Ruijin Hospital, Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China (e-mail: firstname.lastname@example.org) or Weijun Zhou, MD, PhD, Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (e-mail: email@example.com).
Supported by grants from the National Natural Science Foundation of China 81370255.
The authors report no conflicts of interest.
J. Gao and Q. Xie have contributed equally to this work.
Received September 07, 2018
Accepted February 08, 2019