Chronic hypertension increases aortic endothelial hydraulic conductivity by upregulating endothelial aquaporin-1 expression.
Chronic hypertension increases aortic endothelial hydraulic conductivity by upregulating endothelial aquaporin-1 expression.
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慢性高血压通过上调内皮水通道蛋白-1 表达来增加主动脉内皮水力传导率。
DOI：
10.1152/ajpheart.00651.2016
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Rumschitzki,DavidS
中科院分区：
文献类型：
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作者：
Toussaint,Jimmy;Raval,ChiragBharavi;Nguyen,Tieuvi;Fadaifard,Hadi;Joshi,Shripad;Wolberg,George;Quarfordt,Steven;Jan,Kung-Ming;Rumschitzki,DavidS
许多研究已经研究了水通道蛋白在渗透水运输在各种系统中的作用，但几乎没有一个集中在水通道蛋白在涉及哺乳动物细胞的流体静力学驱动的水运输中的作用，除了我们实验室最近的研究主动脉内皮细胞。在这里，我们研究了水通道蛋白-1的表达和功能在两个高血压大鼠模型，自发性高血压基因改变的Wistar-Kyoto大鼠变异体和Sprague-Dawley大鼠高血压的两个肾，一个剪辑Goldblatt手术的主动脉内皮。我们测量水通道蛋白-1的表达，从整个大鼠腹主动脉内皮细胞的定量免疫组化和功能，通过测量压力驱动的液压传导率切除大鼠腹主动脉与完整和裸露的内皮细胞在同一血管。我们用它们来计算有效内膜导水率，这是内皮和内皮下成分的组合。我们观察到相关的增强水通道蛋白-1的表达和功能，在高血压大鼠模型，以及从正常血压大鼠的表达上调2小时的毛喉素治疗的arrhetas。上调水通道蛋白-1的表达和功能可能是高血压的一种反应，它决定了导管动脉血管壁的活力和长期对动脉粥样硬化的易感性。新&值得注意的是，两个高肾素高血压大鼠模型的主动脉内皮细胞表达了大于两倍的水通道蛋白-1，在低压下，具有大于两倍的内皮水力传导率的血压正常大鼠。数据与理论预测一致，即较高的内皮水通道蛋白-1表达提高了内皮下内膜压缩和动脉壁水力传导性下降的临界压力。
Numerous studies have examined the role of aquaporins in osmotic water transport in various systems, but virtually none have focused on the role of aquaporin in hydrostatically driven water transport involving mammalian cells save for our laboratory’s recent study of aortic endothelial cells. Here, we investigated aquaporin-1 expression and function in the aortic endothelium in two high-renin rat models of hypertension, the spontaneously hypertensive genetically altered Wistar-Kyoto rat variant and Sprague-Dawley rats made hypertensive by two-kidney, one-clip Goldblatt surgery. We measured aquaporin-1 expression in aortic endothelial cells from whole rat aortas by quantitative immunohistochemistry and function by measuring the pressure-driven hydraulic conductivities of excised rat aortas with both intact and denuded endothelia on the same vessel. We used them to calculate the effective intimal hydraulic conductivity, which is a combination of endothelial and subendothelial components. We observed well-correlated enhancements in aquaporin-1 expression and function in both hypertensive rat models as well as in aortas from normotensive rats whose expression was upregulated by 2 h of forskolin treatment. Upregulated aquaporin-1 expression and function may be a response to hypertension that critically determines conduit artery vessel wall viability and long-term susceptibility to atherosclerosis.NEW & NOTEWORTHYThe aortic endothelia of two high-renin hypertensive rat models express greater than two times the aquaporin-1 and, at low pressures, have greater than two times the endothelial hydraulic conductivity of normotensive rats. Data are consistent with theory predicting that higher endothelial aquaporin-1 expression raises the critical pressure for subendothelial intima compression and for artery wall hydraulic conductivity to drop.