Alterations of potassium channels in vascular smooth muscle cells and endothelial cells in hypertension

高血压模型大鼠SHR和SHR- sp内皮细胞电压依赖性钾电流降低。我们之前报道过这种改变部分是由于Kv 1.5通道蛋白的表达减少。我们还观察到，对高血压大鼠进行降压治疗可以恢复这种改变。因此，我们假设肾素-血管紧张素系统在钾通道活性的控制中起重要作用。在本研究中，我们观察到与WKY相比，SHR的肠系膜平滑肌细胞中的钾电流减少。与WKY相比，SHR中Kv2.1 mRNA表达量下降，而Kv1.5和Kv1.2 mRNA表达量保持不变。黄嘌呤和黄嘌呤氧化酶对细胞外氧化应激没有影响，但通过记录移液管在细胞内施加NADH和NADPH产生的细胞内氧化应激降低了钾电流。此外，H2DCDA测定的单细胞胞内氧化应激在SHR中比在WKY中增强。最后，SHR组NAD(P)H氧化酶组分NOX4、NOX1、p22 mRNA表达增强。这些结果表明，钾通道表达的减少和氧化应激的增加可能会降低SHR中的钾电流。

Voltage dependent potassium currents in endothelial cells were decreased in hypertensive model rats such as SHR and SHR-SP. We previously reported that this alteration was partially due to the decreased expression of Kv 1.5 channel protein. We also observed that antihypertensive treatment on hypertensive rats restored this alteration. We thus hypothesize that renin-angiotensin system plays an important role on the control of potassium channel activities. In the present study, we observed that potassium currents were decreased in mesenteric smooth muscle cells from SHR, as compared to WKY. mRNA expression of Kv2.1 was decreased in SHR, but that of Kv1.5 and Kv1.2 remained the same as compared to WKY. An extracellular oxidative stress, that was produced by bath application of xanthin and xanthin oxidase, did not affect, but an intracellular oxidative stress, that was produced by intracellular application of NADH and NADPH via recording pipette, decreased potassium currents. In addition, intracellular oxidative stress of single cells as measured with H2DCDA was enhanced in SHR than in WKY. Finally, mRNA expression of component of NAD(P)H oxidase such as NOX4, NOX1, and p22 was enhanced in SHR. These results suggest that decreased expression of potassium channels, and enhanced production of oxidative stress may decrease the potassium currents in SHR.