Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, People's Republic of China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, People's Republic of China; Hubei Key Laboratory of Cardiology, Wuhan 430060, People's Republic of China; Department of Cardiology, Suizhou Hospital, Hubei University of Medicine, Suizhou 441300, People's Republic of China.
Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, People's Republic of China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, People's Republic of China; Hubei Key Laboratory of Cardiology, Wuhan 430060, People's Republic of China.
Nutr Metab Cardiovasc Dis. 2021 May 6;31(5):1635-1644. doi: 10.1016/j.numecd.2021.01.021. Epub 2021 Feb 9.
Our previous study found carotid baroreceptor stimulation (CBS) reduces body weight and white adipose tissue (WAT) weight, restores abnormal secretion of adipocytokines and inflammation factors, decreases systolic blood pressure (SBP) by inhibiting activation of sympathetic nervous system (SNS) and renin-angiotensin system (RAS) in obese rats. In this study, we explore effects of CBS on aortic remodeling in obese rats.
Rats were fed high-fat diet (HFD) for 16 weeks to induce obesity and underwent either CBS device implantation and stimulation or sham operation at 8 weeks. BP and body weight were measured weekly. RAS activity of WAT, histological, biochemical and functional profiles of aortas were detected after 16 weeks. CBS effectively decreased BP in obese rats, downregulated mRNA expression of angiotensinogen (AGT) and renin in WAT, concentrations of AGT, renin, angiotensin II (Ang II), protein levels of Ang II receptor 1 (AT1R) and Ang II receptor 2 (AT2R) in WAT were declined. CBS inhibited reactive oxygen species (ROS) generation, inflammatory response and endoplasmic reticulum (ER) stress in aortas of obese rats, restrained vascular wall thickening and vascular smooth muscle cells (VSMCs) phenotypic switching, increased nitric oxide (NO) synthesis, promoted endothelium-dependent vasodilatation by decreasing protein expression of AT1R and leptin receptor (LepR), increasing protein expression of adiponectin receptor 1 (AdipoR1) in aortic VSMCs.
CBS reduced BP and reversed aortic remodeling in obese rats, the underlying mechanism might be related to the suppressed SNS activity, restored adipocytokine secretion and restrained RAS activity of WAT.
我们之前的研究发现颈动脉压力感受器刺激(CBS)可减轻体重和白色脂肪组织(WAT)重量,通过抑制交感神经系统(SNS)和肾素-血管紧张素系统(RAS)的激活,恢复肥胖大鼠异常的脂肪细胞因子和炎症因子分泌,降低收缩压(SBP)。在本研究中,我们探讨了 CBS 对肥胖大鼠主动脉重塑的影响。
大鼠喂养高脂肪饮食(HFD)16 周以诱导肥胖,并在 8 周时进行 CBS 装置植入和刺激或假手术。每周测量血压和体重。16 周后检测 WAT 的 RAS 活性、主动脉的组织学、生化和功能特征。CBS 有效降低肥胖大鼠的血压,下调 WAT 中血管紧张素原(AGT)和肾素的 mRNA 表达,降低 WAT 中 AGT、肾素、血管紧张素 II(Ang II)、血管紧张素 II 受体 1(AT1R)和血管紧张素 II 受体 2(AT2R)的蛋白水平。CBS 抑制肥胖大鼠主动脉中活性氧(ROS)的产生、炎症反应和内质网(ER)应激,抑制血管壁增厚和血管平滑肌细胞(VSMCs)表型转换,增加一氧化氮(NO)合成,通过降低血管平滑肌细胞中 AT1R 和瘦素受体(LepR)的蛋白表达,增加脂联素受体 1(AdipoR1)的蛋白表达,促进内皮依赖性血管舒张。
CBS 降低了肥胖大鼠的血压并逆转了主动脉重塑,其潜在机制可能与抑制 SNS 活性、恢复脂肪细胞因子分泌和抑制 WAT 的 RAS 活性有关。