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

高血压时血管平滑肌细胞和内皮细胞钾通道的改变

• 批准号: 15590853
• 负责人: OHYA Yusuke
• 金额: $ 1.66万
• 依托单位: University of the Ryukyus
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590853/
• 关键词: Ion channels; Hypertension; Potassium; NADPH oxidase; Oxidative Stress; 血管平滑筋; 内皮細胞; 酸化ストレス; カリウムチャネル; 血管内皮; 血管内

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.

SHR和SHR-SP等高血压模型大鼠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 通道蛋白表达减少所致。我们还观察到，对高血压大鼠进行抗高血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发挥重要作用。在本研究中，我们观察到与 WKY 相比，SHR 肠系膜平滑肌细胞中钾电流降低。与WKY相比，SHR中Kv2.1的mRNA表达降低，但Kv1.5和Kv1.2的mRNA表达保持相同。通过浴液施加黄质和黄质氧化酶产生的细胞外氧化应激不会影响钾电流，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会降低钾电流。此外，用 H2DCDA 测量的单细胞的细胞内氧化应激在 SHR 中比在 WKY 中增强。最后，NAD(P)H 氧化酶成分（如 NOX4、NOX1 和 p22）的 mRNA 表达在 SHR 中增强。这些结果表明，钾通道表达的减少和氧化应激产生的增加可能会降低 SHR 中的钾电流。

项目成果

Central cardiovascular action of urotensin II in spontaneously hypertensive rats

• DOI: 10.1291/hypres.26.839
• 发表时间: 2003-10-01
• 期刊: HYPERTENSION RESEARCH
• 影响因子: 5.4
• 作者: Lin, YZ;Tsuchihashi, T;Iida, M
• 通讯作者: Iida, M

Increased expression of gp91phox homologues of NAD(P)H oxidasein the aortic media during chronic hypertension : Involvement of renin-angiotensin system

慢性高血压期间主动脉中层NAD(P)H氧化酶的gp91phox同源物表达增加：肾素-血管紧张素系统的参与

• 发表时间: 2006
• 期刊: Hypertens Res (In press)
• 作者: Akasaki T;Ohya Y;Kuroda J;et al.
• 通讯作者: et al.

Increased pulse wave velocity is associated with low creatinine clearance and proteinuria in a screened cohort

• DOI: 10.1053/j.ajkd.2006.01.027
• 发表时间: 2006-05-01
• 期刊: AMERICAN JOURNAL OF KIDNEY DISEASES
• 影响因子: 13.2
• 作者: Ohya, Yusuke;Iseki, Kunitoshi;Takishita, Shuichi
• 通讯作者: Takishita, Shuichi

Sympathetic hyperreactivity to air-jet stress in the chromosome 1 blood pressure quantitative trait locus congenic rats

• DOI: 10.1152/ajpregu.00610.2005
• 发表时间: 2006-03-01
• 期刊: AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
• 影响因子: 2.8
• 作者: Yamazato, M;Ohya, Y;Takishita, S
• 通讯作者: Takishita, S

Effect of blood pressure levels after acute stroke on case fatality.

急性中风后血压水平对病死率的影响。

• 发表时间: 2005
• 期刊: J Hypertens. 23
• 作者: Okumura K;Ohya Y;Maehara A;Wakugami K;Iseki K;Takishita S.
• 通讯作者: Takishita S.