Involvement of Angiotensin II Type 1 Receptor and Calcium Channel in Vascular Remodeling and Endothelial Dysfunction in Rats with Pressure Overload
Involvement of Angiotensin II Type 1 Receptor and Calcium Channel in Vascular Remodeling and Endothelial Dysfunction in Rats with Pressure Overload
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DOI：
10.1007/s11596-020-2171-7
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发表时间：
2020-04-01
影响因子：
2.4
通讯作者：
Gao, Ping-jin
中科院分区：
文献类型：
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作者：
Chen, Dong-rui;Jiang, Hui;Gao, Ping-jin
血管重塑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，我们研究血管紧张素Ⅱ 1型受体（AT 1 R）和钙通道在颈动脉重塑中的作用，以响应增加的生物力学力，通过使用横向主动脉缩窄（TAC）大鼠模型。在10周龄雄性Sprague-Dawley大鼠中诱导TAC，并将这些模型用AT 1 R阻断剂奥美沙坦（1 mg/kg/天）或/和钙通道阻断剂（CCB）TBI（0.5 mg/kg/天）处理14天。处理后，收集右侧颈总动脉近端带（RCCA-B）用于进一步测定。结果表明，奥美沙坦，但不是丹参，显着防止TAC诱导的外膜增生。类似地，奥美沙坦（而非奥美沙坦）可显著预防血管炎症，如肿瘤坏死因子α（TNF-α）增加和p65磷酸化增加所示，p65磷酸化是RCCA-B中活化B细胞（NF κ B）活化的核因子κ轻链增强子的指标。相比之下，奥美沙坦和奥沙利铂逆转了内皮型一氧化氮合酶（eNOS）表达的下降，并改善了内皮依赖性血管舒张，而奥美沙坦和奥沙利铂的组合没有显示出进一步的协同保护作用。这些结果表明，AT 1 R参与了血管重塑和炎症反应的压力超负荷，而AT 1 R和随后的钙通道参与内皮功能障碍。
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 alpha (TNF-alpha) and increased p65 phosphorylation, an indicator of nuclear factor kappa-light-chain-enhancer of activated B cells (NF kappa B) 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.