Low-Dose Aspirin Treatment Attenuates Male Rat Salt-Sensitive Hypertension via Platelet Cyclooxygenase 1 and Complement Cascade Pathway
Low-Dose Aspirin Treatment Attenuates Male Rat Salt-Sensitive Hypertension via Platelet Cyclooxygenase 1 and Complement Cascade Pathway
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低剂量阿司匹林治疗通过血小板环加氧酶 1 和补体级联途径减轻雄性大鼠盐敏感性高血压
DOI：
10.1161/jaha.119.013470
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发表时间：
2020-01-07
影响因子：
5.4
通讯作者：
Yang，Zhiwei
中科院分区：
文献类型：
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作者：
Jiang，Xiaoliang;Liu，Xue;Yang，Zhiwei
血小板在高血压发病机制中血管炎症和内皮功能障碍发展中的作用目前已得到很好的证实。阿司匹林具有止痛、退烧、消炎、抑制血小板聚集和防止凝血的作用，但其在盐敏感性高血压中的作用尚不清楚。本研究探讨了阿司匹林在盐敏感性高血压大鼠模型中抑制血小板异常活化和促进血管内皮正常功能的重要性。方法与结果采用正常盐饮食（4% NaCl）、高盐饮食（8% NaCl）或高盐饮食并灌胃阿司匹林（10 mg/kg /天），连续8周，分别饲喂达尔盐敏感大鼠和耐盐大鼠。测量血压、血小板活化、血管功能、炎症反应和潜在机制。低剂量阿司匹林（每天10mg /kg）降低高盐饮食引起的血压升高、血小板活化、白细胞浸润和白细胞-血小板聚集（CD45+CD61+），以及血管内皮和肾脏损害。这些作用与阿司匹林通过抑制血小板环加氧酶1而非环加氧酶2途径阻止白细胞粘附内皮细胞的能力有关。阿司匹林还能逆转高盐饮食诱导的血小板补体和凝血级联反应的异常激活。结论阿司匹林具有改善血小板活化引起的血管内皮功能障碍的新特性，可能有助于治疗盐敏感性高血压。
BackgroundThe role of platelets in the development of vascular inflammation and endothelial dysfunction in the pathogenesis of hypertension is well established at this time. Aspirin is known to relieve pain, decrease fever, reduce inflammation, impair platelet aggregation, and prevent clotting, yet its effect in the context of salt‐sensitive hypertension remains unclear. The present study investigated the importance of aspirin in inhibiting the abnormal activation of platelets and promoting the normal function of the vascular endothelium in a rat model of salt‐sensitive hypertension.Method and ResultsDahl salt‐sensitive rats and salt‐resistant rats were fed a normal‐salt diet (4% NaCl), a high‐salt diet (8% NaCl), or a high‐salt diet with aspirin gavage (10 mg/kg per day) for 8 weeks. Blood pressure, platelet activation, vascular function, inflammatory response, and potential mechanism were measured. Low‐dose aspirin (10 mg/kg per day) decreased the high‐salt diet–induced elevation of blood pressure, platelet activation, leukocyte infiltration, and leukocyte–platelet aggregation (CD45+CD61+), as well as vascular endothelial and renal damage. These effects were related to the ability of aspirin to prevent the adhesion of leukocytes to endothelial cells via inhibition of the platelet cyclooxygenase 1 but not the cyclooxygenase 2 pathway. Aspirin also reversed the high‐salt diet–induced abnormal activation of complement and coagulation cascades in platelets.ConclusionsThese results highlight a new property of aspirin in ameliorating vascular endothelial dysfunction induced by platelet activation, which may be beneficial in the treatment of salt‐sensitive hypertension.