Paternal long-term PM2.5 exposure causes hypertension via increased renal AT1R expression and function in male offspring.
Paternal long-term PM2.5 exposure causes hypertension via increased renal AT1R expression and function in male offspring.
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父亲长期接触 PM2.5 通过增加男性后代肾脏 AT1R 表达和功能导致高血压
DOI：
10.1042/cs20210802
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发表时间：
2021-11-26
期刊：
影响因子：
--
通讯作者：
Zeng C
中科院分区：
文献类型：
--
作者：
Hu C;Tao Y;Deng Y;Cai Q;Ren H;Yu C;Zheng S;Yang J;Zeng C
母亲接触细颗粒物（PM2.5）会导致后代高血压。然而，暴露在PM2.5中的父亲对后代高血压的影响尚不清楚。在本研究中，雄性Sprague-Dawley大鼠用PM2.5悬浮液（10 mg/ml）治疗12周，或用含有抗氧化剂tempol （1 mM/L）的自来水喂养16周。测定雄性子代血压、24小时尿量和钠排泄量。同时给予氯沙坦（20mg /kg/d）治疗4周。采用qRT-PCR和免疫印迹法检测血管紧张素II型1受体（AT1R）和g蛋白偶联受体激酶4 （GRK4）的表达。我们发现，长期暴露于父系大鼠的PM2.5会导致雄性后代高血压、尿量和钠排泄受损。暴露于pm2.5的父本大鼠后代中GRK4及其下游靶点AT1R的mRNA和蛋白表达均增加，这反映在其功能上，因为使用AT1R拮抗剂氯沙坦治疗可以降低血压，增加尿量和钠排泄量。此外，pm2.5处理的雄性大鼠氧化应激水平升高。父系大鼠给药后可恢复暴露于pm2.5的后代血压升高、尿量减少和钠排泄。父系大鼠的tempol治疗也逆转了其后代肾脏中AT1R和GRK4表达的增加。我们认为父亲接触PM2.5会导致后代高血压。其机制可能涉及父亲PM2.5暴露相关的氧化应激诱导肾脏GRK4水平升高，导致AT1R表达增强及其介导的钠潴留，从而导致雄性后代高血压。
Maternal exposure to fine particulate matter (PM2.5) causes hypertension in offspring. However, paternal contribution of PM2.5 exposure to hypertension in offspring remains unknown. In the present study, male Sprague-Dawley rats were treated with PM2.5 suspension (10 mg/ml) for 12 weeks and/or fed with tap water containing an antioxidant tempol (1 mM/L) for 16 weeks. The blood pressure, 24 h-urine volume and sodium excretion were determined in male offspring. The offspring were also administrated with losartan (20 mg/kg/d) for 4 weeks. The expressions of angiotensin II type 1 receptor (AT1R) and G-protein–coupled receptor kinase type 4 (GRK4) were determined by qRT-PCR and immunoblotting. We found that long-term PM2.5 exposure to paternal rats caused hypertension and impaired urine volume and sodium excretion in male offspring. Both the mRNA and protein expression of GRK4 and its downstream target AT1R were increased in offspring of PM2.5-exposed paternal rats, which was reflected in its function because treatment with losartan, an AT1R antagonist, decreased the blood pressure and increased urine volume and sodium excretion. In addition, the oxidative stress level was increased in PM2.5-treated paternal rats. Administration with tempol in paternal rats restored the increased blood pressure and decreased urine volume and sodium excretion in the offspring of PM2.5-exposed paternal rats. Treatment with tempol in paternal rats also reversed the increased expressions of AT1R and GRK4 in the kidney of their offspring. We suggest that paternal PM2.5 exposure causes hypertension in offspring. The mechanism may be involved that paternal PM2.5 exposure-associated oxidative stress induces the elevated renal GRK4 level, leading to the enhanced AT1R expression and its-mediated sodium retention, consequently causes hypertension in male offspring.