AKT participates in endothelial dysfunction in hypertension
AKT participates in endothelial dysfunction in hypertension
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DOI：
10.1161/01.cir.0000129768.35536.fa
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发表时间：
2004-06-01
期刊：
影响因子：
37.8
通讯作者：
Trimarco, B
中科院分区：
文献类型：
--
作者：
Iaccarino, G;Ciccarelli, M;Trimarco, B
背景--在高血压中，可以观察到一氧化氮产生减少和内皮血管舒张减弱.最近有报道称，AKT磷酸化和激活内皮一氧化氮合酶和受损的激酶活性可能参与内皮功能障碍。方法和结果-要确定正常血压的维斯塔-京都大鼠（WKY）和自发性高血压大鼠（SHR）的激酶的生理作用，我们使用腺病毒载体转移人AKT 1基因选择性颈总动脉内皮。在体外，与WKY大鼠相比，SHR对照颈动脉中对乙酰胆碱、异丙肾上腺素和胰岛素的内皮血管舒张作用减弱，而人AKT 1过表达纠正了这些反应。同样地，与WKY颈动脉相比，在体内通过多普勒超声评估的血流在SHR中减少，并且在AKT 1基因转移后恢复正常。在原代培养的内皮细胞中，我们评估了AKT磷酸化，活性和区室化，并观察到的激酶在SHR.Conclusions的错误定位-我们的结论是，AKT参与设置在SHR大鼠内皮功能障碍受损的膜定位。我们的数据表明，AKT参与高血压的内皮功能障碍。
Background - In hypertension, reduced nitric oxide production and blunted endothelial vasorelaxation are observed. It was recently reported that AKT phosphorylates and activates endothelial nitric oxide synthase and that impaired kinase activity may be involved in endothelial dysfunction.Methods and Results - To identify the physiological role of the kinase in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR), we used adenoviral vectors to transfer the human AKT1 gene selectively to the common carotid endothelium. In vitro, endothelial vasorelaxations to acetylcholine, isoproterenol, and insulin were blunted in control carotids from SHR compared with WKY rats, and human AKT1 overexpression corrected these responses. Similarly, blood flow assessed in vivo by Doppler ultrasound was reduced in SHR compared with WKY carotids and normalized after AKT1 gene transfer. In primary cultured endothelial cells, we evaluated AKT phosphorylation, activity, and compartmentalization and observed a mislocalization of the kinase in SHR.Conclusions - We conclude that AKT participates in the settings of endothelial dysfunction in SHR rats by impaired membrane localization. Our data suggest that AKT is involved in endothelium dysfunction in hypertension.