收稿日期: 2025-04-15
网络出版日期: 2025-11-05
基金资助
国家自然科学基金项目(82170133);河南省高等学校重点科研项目(22A310018)
Effect of losartan on high salt intake induced by angiotensin Ⅱ in the locus coeruleus of the brain
Received date: 2025-04-15
Online published: 2025-11-05
目的 通过观察大脑蓝斑核中血管紧张素Ⅱ（angiotensin Ⅱ， Ang Ⅱ）对高盐摄入的影响作用及其氯沙坦对该作用的影响，探讨限盐策略的有效实施方法。 方法 应用大脑插管术和脑微量注射法，给大鼠蓝斑核内单独微量注射Ang Ⅱ，和联合微量注射生理盐水（saline）、Ang Ⅱ和血管紧张素Ⅱ1型受体（angiotensin Ⅱ type 1 receptor， AT1R）拮抗剂氯沙坦（losartan），观察不同摄钠模型大鼠高渗氯化钠溶液的摄入量和摄水量的变化；给大鼠蓝斑核内单独微量注射Ang Ⅱ，观察禁水大鼠水摄入量的变化和正常大鼠尿量和尿钠排泄量、水平和垂直活动度的变化。 结果 无论在给予“禁水-不完全补水（water deprivation-partial rehydration，WD-PR）”模型大鼠，还是在“皮下联合注射呋塞米（furosemide，FURO）与卡托普利（captopril，CAP）（FURO-CAP）”模型大鼠，蓝斑核微量注射0.1、1和10 ng 剂量的Ang Ⅱ引起0.3 mol/L NaCl摄入量和水摄入量都呈剂量相关性增长，而预先注射0.5、5和50 μg剂量的AT1R拮抗剂氯沙坦，以剂量依赖性的方式显著抑制10 ng Ang Ⅱ注射到同一部位所引起的0.3 mol/L NaCl摄入量的增加和水摄入量的增加。与蓝斑核注射saline相比，蓝斑核注射10.0 ng 剂量的Ang Ⅱ显著提高大鼠的水平活动度和垂直活动度，对大鼠肾排泄亦无明显影响。 结论 氯沙坦能抑制大脑蓝斑核Ang Ⅱ所诱导高盐摄入，可作为控制高血压的限盐策略药物治疗方案中一种有效药物。
闫君宝 , 陈义祥 , 牛小艳 , 陆兆丰 . 氯沙坦对大脑蓝斑核中血管紧张素Ⅱ所诱导的高盐摄入的影响[J]. 实用医学杂志, 2025 , 41(20) : 3155 -3164 . DOI: 10.3969/j.issn.1006-5725.2025.20.003
Objective By observing the effect of angiotensin Ⅱ in the locus coeruleus of the brain on high salt intake and the impact of losartan on this effect， this study explores effective implementation methods for salt restriction strategies. Methods Brain catheterization and microinjection were used to administer single microinjection of Ang Ⅱ into the locus coeruleus of rats， as well as combined microinjection of saline， Ang Ⅱ， and angiotensin Ⅱ type 1 receptor， AT1R antagonist losartan was used to observe the changes in the intake and water intake of hypertonic sodium chloride solution in rats with different sodium intake models； Single microinjection of Ang Ⅱ into the locus coeruleus of rats was performed to observe changes in water intake in water deprived rats， as well as changes in urine output， sodium excretion， horizontal and vertical activity in normal rats. Results Whether in rats treated with “water deprivation partial rehydration （WD-PR）” or in rats treated with “subcutaneous combined injection of furosemide （FURO） and Captopril （CAP） （FURO-CAP）”， microinjection of 0.1 ng， 1 ng， and 10 ng doses of Ang Ⅱ into the locus coeruleus caused a dose-dependent increase in 0.3 mol/L NaCl intake and water intake. However， pre injection of AT1R antagonist losartan at doses of 0.5 μ g， 5 μ g， and 50 μ g significantly inhibited the injection of 10 ng Ang Ⅱ into the same site in a dose-dependent manner. The increase in intake of 0.3 mol/L NaCl and water caused by it. Compared with injection of saline into the locus coeruleus， injection of 10.0ng dose of Ang Ⅱ into the locus coeruleus significantly increased the horizontal and vertical activity of rats， but had no significant effect on renal excretion. Conclusion Losartan can inhibit the high salt intake induced by Ang Ⅱ in the locus coeruleus of the brain， and can be used as an effective drug in the salt limiting strategy for controlling hypertension.
Key words： locus coeruleus; Ang Ⅱ; losartan; high sodium intake; renal excretion; activity level
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