State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Shanghai Institute of Hypertension, Shanghai, 200025, China.
Curr Med Sci. 2020 Apr;40(2):320-326. doi: 10.1007/s11596-020-2171-7. Epub 2020 Apr 26.
Vascular remodeling is an adaptive response to various stimuli, including mechanical forces, inflammatory cytokines and hormones. In the present study, we investigated the role of angiotensin II type 1 receptor (AT1R) and calcium channel in carotid artery remodeling in response to increased biomechanical forces by using the transverse aortic constriction (TAC) rat model. TAC was induced on ten-week-old male Sprague-Dawley rats and these models were treated with AT1R blocker olmesartan (1 mg/kg/day) or/and calcium channel blocker (CCB) amlodipine (0.5 mg/kg/day) for 14 days. After the treatment, the right common carotid artery proximal to the band (RCCA-B) was collected for further assay. Results showed that olmesartan, but not amlodipine, significantly prevented TAC-induced adventitial hyperplasia. Similarly, olmesartan, but not amlodipine, signifcantly prevented vascular infammation, as indicated by increased tumor necrosis factor α (TNF-α) and increased p65 phosphorylation, an indicator of nuclear factor κ-light-chain-enhancer of activated B cells (NFκB) activation in RCCA-B. In contrast, both olmesartan and amlodipine reversed the decreased expression of endothelial nitric oxidase synthase (eNOS) and improved endothelium-dependent vasodilation, whereas combination of olmesartan and amlodipine showed no further synergistic protective effects. These results suggest that AT1R was involved in vascular remodeling and inflammation in response to pressure overload, whereas AT1R and subsequent calcium channel were involved in endothelial dysfunction.
血管重构是对各种刺激的适应性反应，包括机械力、炎性细胞因子和激素。在本研究中，我们通过使用腹主动脉缩窄（TAC）大鼠模型，研究了血管紧张素 II 型 1 型受体（AT1R）和钙通道在应对增加的生物力学力时对颈动脉重构的作用。在 10 周龄雄性 Sprague-Dawley 大鼠上诱导 TAC，并对这些模型用 AT1R 阻滞剂奥美沙坦（1mg/kg/天）和/或钙通道阻滞剂氨氯地平（0.5mg/kg/天）处理 14 天。治疗后，收集右侧颈总动脉近带（RCCA-B）进行进一步检测。结果表明，奥美沙坦而非氨氯地平可显著预防 TAC 引起的外膜增生。同样，奥美沙坦而非氨氯地平可显著预防血管炎症，这表现为 RCCA-B 中肿瘤坏死因子-α（TNF-α）增加和 p65 磷酸化增加，这是核因子 κB 激活的指标。相反，奥美沙坦和氨氯地平均逆转了内皮型一氧化氮合酶（eNOS）的表达减少，并改善了内皮依赖性血管舒张，而奥美沙坦和氨氯地平联合使用则没有进一步的协同保护作用。这些结果表明，AT1R 参与了压力超负荷时的血管重构和炎症反应，而 AT1R 和随后的钙通道参与了内皮功能障碍。
